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Sample records for ah1n1pdm09 virus infection

  1. Influenza A(H1N1)pdm09 virus infection in giant pandas, China.

    PubMed

    Li, Desheng; Zhu, Ling; Cui, Hengmin; Ling, Shanshan; Fan, Shengtao; Yu, Zhijun; Zhou, Yuancheng; Wang, Tiecheng; Qian, Jun; Xia, Xianzhu; Xu, Zhiwen; Gao, Yuwei; Wang, Chengdong

    2014-03-01

    We confirmed infection with influenza A(H1N1)pdm09 in giant pandas in China during 2009 by using virus isolation and serologic analysis methods. This finding extends the host range of influenza viruses and indicates a need for increased surveillance for and control of influenza viruses among giant pandas. PMID:24565026

  2. Contact tracing for influenza A(H1N1)pdm09 virus-infected passenger on international flight.

    PubMed

    Shankar, Ananda G; Janmohamed, Kulsum; Olowokure, Babatunde; Smith, Gillian E; Hogan, Angela H; De Souza, Valerie; Wallensten, Anders; Oliver, Isabel; Blatchford, Oliver; Cleary, Paul; Ibbotson, Sue

    2014-01-01

    In April 2009, influenza A(H1N1)pdm09 virus infection was confirmed in a person who had been symptomatic while traveling on a commercial flight from Mexico to the United Kingdom. Retrospective public health investigation and contact tracing led to the identification of 8 additional confirmed cases among passengers and community contacts of passengers. PMID:24377724

  3. Natural A(H1N1)pdm09 influenza virus infection case in a pet ferret in Taiwan.

    PubMed

    Lin, Hui-Ting; Wang, Ching-Ho; Wu, Wen-Ling; Chi, Chau-Hwa; Wang, Lih Chiann

    2014-11-01

    Ferrets have demonstrated high susceptibility to the influenza virus. This study discusses a natural 2009 pandemic influenza A (H1N1) (A(H1N1)pdm09) virus infection in a pet ferret (Mustela putorius furo) identified in Taiwan in 2013. The ferret was in close contact with family members who had recently experienced an influenza-like illness (ILI). The ferret nasal swab showed positive results for influenza A virus using one-step RT-PCR. The virus was isolated and the phylogenetic analysis indicated that all of the eight segmented genes were closely related to the human A(H1N1)pdm09 virus linage isolated in Taiwan. This study may provide a perspective view on natural influenza A virus transmission from the local human population into pet ferrets. PMID:25597188

  4. Outcomes of Influenza A(H1N1)pdm09 Virus Infection: Results from Two International Cohort Studies

    PubMed Central

    Lynfield, Ruth; Davey, Richard; Dwyer, Dominic E.; Losso, Marcelo H.; Wentworth, Deborah; Cozzi-Lepri, Alessandro; Herman-Lamin, Kathy; Cholewinska, Grazyna; David, Daniel; Kuetter, Stefan; Ternesgen, Zelalem; Uyeki, Timothy M.; Lane, H. Clifford; Lundgren, Jens; Neaton, James D.

    2014-01-01

    Background Data from prospectively planned cohort studies on risk of major clinical outcomes and prognostic factors for patients with influenza A(H1N1)pdm09 virus are limited. In 2009, in order to assess outcomes and evaluate risk factors for progression of illness, two cohort studies were initiated: FLU 002 in outpatients and FLU 003 in hospitalized patients. Methods and Findings Between October 2009 and December 2012, adults with influenza-like illness (ILI) were enrolled; outpatients were followed for 14 days and inpatients for 60 days. Disease progression was defined as hospitalization and/or death for outpatients, and hospitalization for >28 days, transfer to intensive care unit (ICU) if enrolled from general ward, and/or death for inpatients. Infection was confirmed by RT-PCR. 590 FLU 002 and 392 FLU 003 patients with influenza A (H1N1)pdm09 were enrolled from 81 sites in 17 countries at 2 days (IQR 1–3) and 6 days (IQR 4–10) following ILI onset, respectively. Disease progression was experienced by 29 (1 death) outpatients (5.1%; 95% CI: 3.4–7.2%) and 80 inpatients [death (32), hospitalization >28 days (43) or ICU transfer (20)] (21.6%; 95% CI: 17.5–26.2%). Disease progression (death) for hospitalized patients was 53.1% (26.6%) and 12.8% (3.8%), respectively, for those enrolled in the ICU and general ward. In pooled analyses for both studies, predictors of disease progression were age, longer duration of symptoms at enrollment and immunosuppression. Patients hospitalized during the pandemic period had a poorer prognosis than in subsequent seasons. Conclusions Patients with influenza A(H1N1)pdm09, particularly when requiring hospital admission, are at high risk for disease progression, especially if they are older, immunodeficient, or admitted late in infection. These data reinforce the need for international trials of novel treatment strategies for influenza infection and serve as a reminder of the need to monitor the severity of seasonal and pandemic

  5. Production impact of influenza A(H1N1)pdm09 virus infection on fattening pigs in Norway.

    PubMed

    Er, Chiek; Skjerve, Eystein; Brun, Edgar; Hofmo, Peer Ola; Framstad, Tore; Lium, Bjørn

    2016-02-01

    Newly emerged influenza A(H1N1)pdm09 virus infection in Norwegian pigs, although often observed in a subclinical form, can lower the pig's growth performance by reducing feed efficiency in terms of a poorer feed conversion ratio. Infected pigs would consume more feed and require protracted production time to reach market weight. In our observational longitudinal study, growth performance data from 728 control pigs and 193 infected pigs with known viral shedding time points were analyzed using mixed linear regression models to give estimates of the marginal effects of infection. Gaussian curves describing the variability of the estimates at the individual pig level formed the fundamental inputs to our stochastic models. The models were constructed to simulate the summed negative effects of the infection at the batch level of 150 fattening pigs growing from 33 to 100 kg. Other inputs of variability and uncertainty were 1) batch transmission points, 2) pig infection points to reflect the disease transmission dynamics of the virus, and 3) final prevalence of infected pigs in the batch. Monte Carlo random sampling gave 5,000 estimates on the outputs of the marginal effects for each pig. These results were summed up to provide estimates for a batch size of 150 pigs. This figure was adjusted by our final prevalence distribution function, which was also derived from the longitudinal study with 12 cohorts of infected pigs. For a 150-fattening-pig herd randomly selected from the population, the marginal effects of the infection were 1) 835 kg (fifth percentile) to 1,350 kg (95th percentile) increased feed intake and 2) 194 (fifth percentile) to 334 (95th percentile) pig days in excess of expected figures for an uninfected batch. A batch infected during growth phase 3 (81 to 100 kg BW) gave the worst results since the longitudinal study showed that a pig infected during growth phase 3 required more feed and a greater protracted production time compared to younger infected

  6. High Rate of A(H1N1)pdm09 Infections among Rural Thai Villagers, 2009–2010

    PubMed Central

    Khuntirat, Benjawan; Yoon, In-Kyu; Chittaganpitch, Malinee; Krueger, Whitney S.; Supawat, Krongkaew; Blair, Patrick J.; Putnam, Shannon D.; Gibbons, Robert V.; Buddhari, Darunee; Sawanpanyalert, Pathom; Heil, Gary L.; Friary, John A.; Gray, Gregory C.

    2014-01-01

    Background Pandemic influenza A(H1N1)pdm09 emerged in Thailand in 2009. A prospective longitudinal adult cohort and household transmission study of influenza-like illness (ILI) was ongoing in rural Thailand at the time of emergence. Symptomatic and subclinical A(H1N1)pdm09 infection rates in the cohort and among household members were evaluated. Methods A cohort of 800 Thai adults underwent active community-based surveillance for ILI from 2008–2010. Acute respiratory samples from ILI episodes were tested for A(H1N1)pdm09 by qRT-PCR; acute and 60-day convalescent blood samples were tested by A(H1N1)pdm09 hemagglutination inhibition assay (HI). Enrollment, 12-month and 24-month follow-up blood samples were tested for A(H1N1)pdm09 seroconversion by HI. Household members of influenza A-infected cohort subjects with ILI were enrolled in household transmission investigations in which day 0 and 60 blood samples and acute respiratory samples were tested by either qRT-PCR or HI for A(H1N1)pdm09. Seroconversion between annual blood samples without A(H1N1)pdm09-positive ILI was considered as subclinical infection. Results The 2-yr cumulative incidence of A(H1N1)pdm09 infection in the cohort in 2009/2010 was 10.8% (84/781) with an annual incidence of 1.2% in 2009 and 9.7% in 2010; 83.3% of infections were subclinical (50% in 2009 and 85.9% in 2010). The 2-yr cumulative incidence was lowest (5%) in adults born ≤1957. The A(H1N1)pdm09 secondary attack rate among household contacts was 47.2% (17/36); 47.1% of these infections were subclinical. The highest A(H1N1)pdm09 secondary attack rate among household contacts (70.6%, 12/17) occurred among children born between 1990 and 2003. Conclusion Subclinical A(H1N1)pdm09 infections in Thai adults occurred frequently and accounted for a greater proportion of all A(H1N1)pdm09 infections than previously estimated. The role of subclinical infections in A(H1N1)pdm09 transmission has important implications in formulating strategies to

  7. Oseltamivir-Resistant Influenza A(H1N1)pdm09 Viruses, United States, 2013–14

    PubMed Central

    Okomo-Adhiambo, Margaret; Fry, Alicia M.; Su, Su; Nguyen, Ha T.; Elal, Anwar Abd; Negron, Elizabeth; Hand, Julie; Garten, Rebecca J.; Barnes, John; Xiyan, Xu; Villanueva, Julie M.

    2015-01-01

    We report characteristics of oseltamivir-resistant influenza A(H1N1)pdm09 viruses and patients infected with these viruses in the United States. During 2013–14, fifty-nine (1.2%) of 4,968 analyzed US influenza A(H1N1)pdm09 viruses had the H275Y oseltamivir resistance–conferring neuraminidase substitution. Our results emphasize the need for local surveillance for neuraminidase inhibitor susceptibility among circulating influenza viruses. PMID:25532050

  8. Protein profiling of nasopharyngeal aspirates of hospitalized and outpatients revealed cytokines associated with severe influenza A(H1N1)pdm09 virus infections: A pilot study.

    PubMed

    Fu, Yu; Gaelings, Lana; Jalovaara, Petri; Kakkola, Laura; Kinnunen, Mervi T; Kallio-Kokko, Hannimari; Valkonen, Miia; Kantele, Anu; Kainov, Denis E

    2016-10-01

    Influenza A viruses (IAV) mutate rapidly and cause seasonal epidemics and occasional pandemics, which result in substantial number of patient visits to the doctors and even hospitalizations. We aimed here to identify inflammatory proteins, which levels correlated to clinical severity of the disease. For this we analysed 102 cytokines and growth factors in human nasopharyngeal aspirate (NPA) samples of 27 hospitalized and 27 outpatients diagnosed with influenza A(H1N1)pdm09 virus infection. We found that the relative levels of monocyte differentiation antigen CD14, lipocalin-2 (LCN2), C-C-motif chemokine 20 (CCL20), CD147, urokinase plasminogen activator surface receptor (uPAR), pro-epidermal growth factor (EGF), trefoil factor 3 (TFF3), and macrophage migration inhibitory factor (MIF) were significantly lower (p<0.008), whereas levels of retinol-binding protein 4 (RBP4), C-X-C motif chemokine 5 (CXCL5), interleukin-8 (IL-8), complement factor D (CFD), adiponectin, and chitinase-3-like 1 (CHI3L1) were significantly higher (p<0.008) in NPA samples of hospitalized than non-hospitalized patients. While changes in CD14, LCN2, CCL20, uPAR, EGF, MIF, CXCL5, IL-8, adiponectin and CHI3L1 levels have already been correlated with severity of IAV infection in mice and humans, our study is the first to describe association of CD147, RBP4, TFF3, and CFD with hospitalization of IAV-infected patients. Thus, we identified local innate immune profiles, which were associated with the clinical severity of influenza infections. PMID:27442005

  9. Seroprevalence of influenza A(H1N1)pdm09 virus antibody, England, 2010 and 2011.

    PubMed

    Hoschler, Katja; Thompson, Catherine; Andrews, Nick; Galiano, Monica; Pebody, Richard; Ellis, Joanna; Stanford, Elaine; Baguelin, Marc; Miller, Elizabeth; Zambon, Maria

    2012-11-01

    The intense influenza activity in England during the 2010-11 winter resulted from a combination of factors. Population-based seroepidemiology confirms that the third wave of influenza A(H1N1)pdm09 virus circulation was associated with a shift in age groups affected, with the highest rate of infection in young adults. PMID:23092684

  10. Seroprevalence of Influenza A(H1N1)pdm09 Virus Antibody, England, 2010 and 2011

    PubMed Central

    Thompson, Catherine; Andrews, Nick; Galiano, Monica; Pebody, Richard; Ellis, Joanna; Stanford, Elaine; Baguelin, Marc; Miller, Elizabeth; Zambon, Maria

    2012-01-01

    The intense influenza activity in England during the 2010–11 winter resulted from a combination of factors. Population-based seroepidemiology confirms that the third wave of influenza A(H1N1)pdm09 virus circulation was associated with a shift in age groups affected, with the highest rate of infection in young adults. PMID:23092684

  11. Estimating the fitness advantage conferred by permissive neuraminidase mutations in recent oseltamivir-resistant A(H1N1)pdm09 influenza viruses.

    PubMed

    Butler, Jeff; Hooper, Kathryn A; Petrie, Stephen; Lee, Raphael; Maurer-Stroh, Sebastian; Reh, Lucia; Guarnaccia, Teagan; Baas, Chantal; Xue, Lumin; Vitesnik, Sophie; Leang, Sook-Kwan; McVernon, Jodie; Kelso, Anne; Barr, Ian G; McCaw, James M; Bloom, Jesse D; Hurt, Aeron C

    2014-04-01

    Oseltamivir is relied upon worldwide as the drug of choice for the treatment of human influenza infection. Surveillance for oseltamivir resistance is routinely performed to ensure the ongoing efficacy of oseltamivir against circulating viruses. Since the emergence of the pandemic 2009 A(H1N1) influenza virus (A(H1N1)pdm09), the proportion of A(H1N1)pdm09 viruses that are oseltamivir resistant (OR) has generally been low. However, a cluster of OR A(H1N1)pdm09 viruses, encoding the neuraminidase (NA) H275Y oseltamivir resistance mutation, was detected in Australia in 2011 amongst community patients that had not been treated with oseltamivir. Here we combine a competitive mixtures ferret model of influenza infection with a mathematical model to assess the fitness, both within and between hosts, of recent OR A(H1N1)pdm09 viruses. In conjunction with data from in vitro analyses of NA expression and activity we demonstrate that contemporary A(H1N1)pdm09 viruses are now more capable of acquiring H275Y without compromising their fitness, than earlier A(H1N1)pdm09 viruses circulating in 2009. Furthermore, using reverse engineered viruses we demonstrate that a pair of permissive secondary NA mutations, V241I and N369K, confers robust fitness on recent H275Y A(H1N1)pdm09 viruses, which correlated with enhanced surface expression and enzymatic activity of the A(H1N1)pdm09 NA protein. These permissive mutations first emerged in 2010 and are now present in almost all circulating A(H1N1)pdm09 viruses. Our findings suggest that recent A(H1N1)pdm09 viruses are now more permissive to the acquisition of H275Y than earlier A(H1N1)pdm09 viruses, increasing the risk that OR A(H1N1)pdm09 will emerge and spread worldwide. PMID:24699865

  12. Prevalence of Influenza A(H1N1)pdm09 Virus Resistant to Oseltamivir in Shiraz, Iran, During 2012 - 2013

    PubMed Central

    Khodadad, Nastaran; Moattari, Afagh; Shamsi Shahr Abadi, Mahmoud; Kadivar, Mohammad Rahim; Sarvari, Jamal; Tavakoli, Forough; Pirbonyeh, Neda; Emami, Amir

    2015-01-01

    Background: Oseltamivir has been used as a drug of choice for the prophylaxis and treatment of human influenza A(H1N1)pdm09 infection across the world. However, the most frequently identified oseltamivir resistant virus, influenza A(H1N1)pdm09, exhibit the H275Y substitution in NA gene. Objectives: This study aimed to determine the prevalence and phylogenetic relationships of oseltamivir resistance in influenza A(H1N1)pdm09 viruses isolated in Shiraz, Iran. Patients and Methods: Throat swab samples were collected from 200 patients with influenza-like disease from December 2012 until February 2013. A total of 77 influenza A(H1N1)pdm09 positive strains were identified by real-time polymerase chain reaction (PCR). Oseltamivir resistance was detected using quantal assay and nested-PCR method. The NA gene sequencing was conducted to detect oseltamivir-resistant mutants and establish the phylogeny of the prevalent influenza variants. Results: Our results revealed that A(H1N1)pdm09 viruses present in these samples were susceptible to oseltamivir, and contained 5 site specific mutations (V13G, V106I, V241I, N248D, and N369K) in NA gene. These mutations correlated with increasing expression and enzymatic activity of NA protein in the influenza A(H1N1)pdm09 viruses, which were closely related to a main influenza A(H1N1)pdm09 cluster isolated around the world. Conclusions: A(H1N1)pdm09 viruses, identified in this study in Shiraz, Iran, contained 5 site specific mutations and were susceptible to oseltamivir. PMID:26464773

  13. Influenza A(H1N1)pdm09 virus in pigs, Togo, 2013

    PubMed Central

    Ducatez, Mariette F.; Awoume, Félix; Webby, Richard J.

    2015-01-01

    We collected 325 nasal swabs from freshly slaughtered previously healthy pigs from October 2012 through January 2014 in a slaughterhouse near Lomé in Togo. Influenza A virus genome was detected by RT-PCR in 2.5% to 12.3% of the pooled samples, and results of hemagglutinin subtyping RT-PCR assays showed the virus in all the positive pools to be A(H1N1)pdm09. Virus was isolated on MDCK cells from a representative specimen, A/swine/Togo/ONA32/2013(H1N1). The isolate was fully sequenced and harbored 8 genes similar to A(H1N1)pdm09 virus genes circulating in humans in 2012–2013, suggesting human-to-swine transmission of the pathogen. PMID:25778544

  14. Seropositivity for Influenza A(H1N1)pdm09 Virus among Frontline Health Care Personnel

    PubMed Central

    Alagappan, Kumar; Hancock, Kathy; Ward, Mary Frances; Akerman, Meredith; Dawood, Fatimah S.; Branch, Alicia; De Cicco, Sandra; Steward-Clark, Evelene; McCullough, Megan; Tenner, Karen; Katz, Jacqueline M.

    2013-01-01

    Seroprevalence of antibodies to influenza A(H1N1)pdm09 virus among 193 emergency department health care personnel was similar among 147 non–health care personnel (odds ratio 1.4, 95% CI 0.8–2.4). Working in an acute care setting did not substantially increase risk for virus infection above risk conferred by community-based exposures. PMID:23260627

  15. Full Genome Analysis of Influenza A(H1N1)pdm09 Virus Isolated from Peru, 2013.

    PubMed

    Padilla, Carlos; Condori, Fredy; Huaringa, Maribel; Marcos, Pool; Rojas, Nancy; Gutierrez, Victoria; Cáceres, Omar

    2014-01-01

    The pandemic influenza A(H1N1)pdm09 virus has been reported in Peru since 2009. We report the whole-genome sequence analysis of a viral isolate from an infection case that occurred during an influenza outbreak in 2013. This strain shows novel hemagglutinin (HA) mutations that may cause an antigenic drift that diminishes the protective effect of the vaccine. PMID:24744325

  16. Adaptation of influenza A(H1N1)pdm09 virus in experimental mouse models.

    PubMed

    Prokopyeva, E A; Sobolev, I A; Prokopyev, M V; Shestopalov, A M

    2016-04-01

    In the present study, three mouse-adapted variants of influenza A(H1N1)pdm09 virus were obtained by lung-to-lung passages of BALB/c, C57BL/6z and CD1 mice. The significantly increased virulence and pathogenicity of all of the mouse-adapted variants induced 100% mortality in the adapted mice. Genetic analysis indicated that the increased virulence of all of the mouse-adapted variants reflected the incremental acquisition of several mutations in PB2, PB1, HA, NP, NA, and NS2 proteins. Identical amino acid substitutions were also detected in all of the mouse-adapted variants of A(H1N1)pdm09 virus, including PB2 (K251R), PB1 (V652A), NP (I353V), NA (I106V, N248D) and NS1 (G159E). Apparently, influenza A(H1N1)pdm09 virus easily adapted to the host after serial passages in the lungs, inducing 100% lethality in the last experimental group. However, cross-challenge revealed that not all adapted variants are pathogenic for different laboratory mice. Such important results should be considered when using the influenza mice model. PMID:26829383

  17. The Spread of Influenza A(H1N1)pdm09 Virus in Madagascar Described by a Sentinel Surveillance Network

    PubMed Central

    Rajatonirina, Soatiana; Heraud, Jean-Michel; Orelle, Arnaud; Randrianasolo, Laurence; Razanajatovo, Norosoa; Rajaona, Yolande Raoelina; Randrianarivo-Solofoniaina, Armand Eugène; Rakotomanana, Fanjasoa; Richard, Vincent

    2012-01-01

    Background The influenza A(H1N1)pdm09 virus has been a challenge for public health surveillance systems in all countries. In Antananarivo, the first imported case was reported on August 12, 2009. This work describes the spread of A(H1N1)pdm09 in Madagascar. Methods The diffusion of influenza A(H1N1)pdm09 in Madagascar was explored using notification data from a sentinel network. Clinical data were charted to identify peaks at each sentinel site and virological data was used to confirm viral circulation. Results From August 1, 2009 to February 28, 2010, 7,427 patients with influenza-like illness were reported. Most patients were aged 7 to 14 years. Laboratory tests confirmed infection with A(H1N1)pdm09 in 237 (33.2%) of 750 specimens. The incidence of patients differed between regions. By determining the epidemic peaks we traced the diffusion of the epidemic through locations and time in Madagascar. The first peak was detected during the epidemiological week 47-2009 in Antananarivo and the last one occurred in week 07-2010 in Tsiroanomandidy. Conclusion Sentinel surveillance data can be used for describing epidemic trends, facilitating the development of interventions at the local level to mitigate disease spread and impact. PMID:22615893

  18. A Large Proportion of the Mexican Population Remained Susceptible to A(H1N1)pdm09 Infection One Year after the Emergence of 2009 Influenza Pandemic

    PubMed Central

    Veguilla, Vic; López-Gatell, Hugo; López-Martínez, Irma; Aparicio-Antonio, Rodrigo; Barrera-Badillo, Gisela; Rojo-Medina, Julieta; Gross, Felicia Liaini; Jefferson, Stacie N.; Katz, Jacqueline M.; Hernández-Ávila, Mauricio; Alpuche-Aranda, Celia M.

    2016-01-01

    Background The 2009 H1N1 influenza pandemic initially affected Mexico from April 2009 to July 2010. By August 2010, a fourth of the population had received the monovalent vaccine against the pandemic virus (A(H1N1)pdm09). To assess the proportion of the Mexican population who remained potentially susceptible to infection throughout the summer of 2010, we estimated the population seroprevalence to A(H1N1)pdm09 in a serosurvey of blood donors. Methods We evaluated baseline cross-reactivity to the pandemic strain and set the threshold for seropositivity using pre-pandemic (2005–2008) stored serum samples and sera from confirmed A(H1N1)pdm09 infected individuals. Between June and September 2010, a convenience sample serosurvey of adult blood donors, children, and adolescents was conducted in six states of Mexico. Sera were tested by the microneutralization (MN) and hemagglutination inhibition (HI) assays, and regarded seropositive if antibody titers were equal or exceeded 1:40 for MN and 1:20 for HI. Age-standardized seroprevalence were calculated using the 2010 National Census population. Results Sera from 1,484 individuals were analyzed; 1,363 (92%) were blood donors, and 121 (8%) children or adolescents aged ≤19 years. Mean age (standard deviation) was 31.4 (11.5) years, and 276 (19%) were women. A total of 516 (35%) participants declared history of influenza vaccination after April 2009. The age-standardized seroprevalence to A(H1N1)pdm09 was 48% by the MN and 41% by the HI assays, respectively. The youngest quintile, aged 1 to 22 years, had the highest the seroprevalence; 61% (95% confidence interval [CI]: 56, 66%) for MN, and 56% (95% CI: 51, 62%) for HI. Conclusions Despite high transmission of A(H1N1)pdm09 observed immediately after its emergence and extensive vaccination, over a half of the Mexican population remained potentially susceptible to A(H1N1)pdm09 infection. Subsequent influenza seasons with high transmission of A(H1N1)pdm09, as 2011–2012 and

  19. Structural characterization of a protective epitope spanning A(H1N1)pdm09 influenza virus neuraminidase monomers

    PubMed Central

    Wan, Hongquan; Yang, Hua; Shore, David A.; Garten, Rebecca J.; Couzens, Laura; Gao, Jin; Jiang, Lianlian; Carney, Paul J.; Villanueva, Julie; Stevens, James; Eichelberger, Maryna C.

    2015-01-01

    A(H1N1)pdm09 influenza A viruses predominated in the 2013–2014 USA influenza season, and although most of these viruses remain sensitive to Food and Drug Administration-approved neuraminidase (NA) inhibitors, alternative therapies are needed. Here we show that monoclonal antibody CD6, selected for binding to the NA of the prototypic A(H1N1)pdm09 virus, A/California/07/2009, protects mice against lethal virus challenge. The crystal structure of NA in complex with CD6 Fab reveals a unique epitope, where the heavy-chain complementarity determining regions (HCDRs) 1 and 2 bind one NA monomer, the light-chain CDR2 binds the neighbouring monomer, whereas HCDR3 interacts with both monomers. This 30-amino-acid epitope spans the lateral face of an NA dimer and is conserved among circulating A(H1N1)pdm09 viruses. These results suggest that the large, lateral CD6 epitope may be an effective target of antibodies selected for development as therapeutic agents against circulating H1N1 influenza viruses. PMID:25668439

  20. Pandemic influenza A(H1N1)pdm09: risk of infection in primary healthcare workers

    PubMed Central

    Hudson, Ben; Toop, Les; Mangin, Dee; Brunton, Cheryl; Jennings, Lance; Fletcher, Lynn

    2013-01-01

    Background Healthcare workers in primary care are at risk of infection during an influenza pandemic. The 2009 influenza pandemic provided an opportunity to assess this risk. Aim To measure the prevalence of seropositivity to influenza A(H1N1)pdm09 among primary healthcare workers in Canterbury, New Zealand, following the 2009 influenza pandemic, and to examine associations between seropositivity and participants’ sociodemographic characteristics, professional roles, work patterns, and seasonal influenza vaccination status. Design and setting An observational study involving a questionnaire and testing for influenza A(H1N1)pdm09 seropositivity in all primary healthcare workers in Canterbury, New Zealand between December 2009 and February 2010. Method Participants completed a questionnaire that recorded sociodemographic and professional data, symptoms of influenza-like illness, history of seasonal influenza vaccination, and work patterns. Serum samples were collected and haemagglutination inhibition antibody titres to influenza A(H1N1)pdm09 measured. Results Questionnaires and serum samples were received from 1027 participants, from a workforce of 1476 (response rate 70%). Seropositivity was detected in 224 participants (22%). Receipt of seasonal influenza vaccine (odds ratio [OR] = 2.0, 95% confidence interval [CI] = 1.2 to 3.3), recall of influenza (OR = 1.9, 95% CI = 1.3 to 2.8), and age ≤45 years (OR = 1.4, 95% CI = 1.0 to 1.9) were associated with seropositivity. Conclusion A total of 22% of primary care healthcare workers were seropositive. Younger participants, those who recalled having influenza, and those who had been vaccinated against seasonal influenza were more likely to be seropositive. Working in a dedicated influenza centre was not associated with an increased risk of seropositivity. PMID:23735413

  1. Diverse antigenic site targeting of influenza hemagglutinin in the murine antibody recall response to A(H1N1)pdm09 virus.

    PubMed

    Wilson, Jason R; Guo, Zhu; Tzeng, Wen-Pin; Garten, Rebecca J; Xiyan, Xu; Blanchard, Elisabeth G; Blanchfield, Kristy; Stevens, James; Katz, Jacqueline M; York, Ian A

    2015-11-01

    Here we define the epitopes on HA that are targeted by a group of 9 recombinant monoclonal antibodies (rmAbs) isolated from memory B cells of mice, immunized by infection with A(H1N1)pdm09 virus followed by a seasonal TIV boost. These rmAbs were all reactive against the HA1 region of HA, but display 7 distinct binding footprints, targeting each of the 4 known antigenic sites. Although the rmAbs were not broadly cross-reactive, a group showed subtype-specific cross-reactivity with the HA of A/South Carolina/1/18. Screening these rmAbs with a panel of human A(H1N1)pdm09 virus isolates indicated that naturally-occurring changes in HA could reduce rmAb binding, HI activity, and/or virus neutralization activity by rmAb, without showing changes in recognition by polyclonal antiserum. In some instances, virus neutralization was lost while both ELISA binding and HI activity were retained, demonstrating a discordance between the two serological assays traditionally used to detect antigenic drift. PMID:26318247

  2. Protection by Face Masks against Influenza A(H1N1)pdm09 Virus on Trans-Pacific Passenger Aircraft, 2009

    PubMed Central

    Zhang, Lijie; Peng, Zhibin; Ou, Jianming; Zeng, Guang; Fontaine, Robert E.; Liu, Mingbin; Cui, Fuqiang; Hong, Rongtao; Zhou, Hang; Huai, Yang; Chuang, Shuk-Kwan; Leung, Yiu-Hong; Feng, Yunxia; Luo, Yuan; Shen, Tao; Zhu, Bao-Ping; Widdowson, Marc-Alain

    2013-01-01

    In response to several influenza A(H1N1)pdm09 infections that developed in passengers after they traveled on the same 2 flights from New York, New York, USA, to Hong Kong, China, to Fuzhou, China, we assessed transmission of influenza A(H1N1)pdm09 virus on these flights. We defined a case of infection as onset of fever and respiratory symptoms and detection of virus by PCR in a passenger or crew member of either flight. Illness developed only in passengers who traveled on the New York to Hong Kong flight. We compared exposures of 9 case-passengers with those of 32 asymptomatic control-passengers. None of the 9 case-passengers, compared with 47% (15/32) of control-passengers, wore a face mask for the entire flight (odds ratio 0, 95% CI 0–0.71). The source case-passenger was not identified. Wearing a face mask was a protective factor against influenza infection. We recommend a more comprehensive intervention study to accurately estimate this effect. PMID:23968983

  3. Reconstruction of the Evolutionary Dynamics of the A(H1N1)pdm09 Influenza Virus in Italy during the Pandemic and Post-Pandemic Phases

    PubMed Central

    Zehender, Gianguglielmo; Lai, Alessia; Gabanelli, Elena; Ranghiero, Alberto; Ebranati, Erika; Amendola, Antonella; Campanini, Giulia; Rovida, Francesca; Ciccozzi, Massimo; Galli, Massimo; Baldanti, Fausto; Zanetti, Alessandro Remo

    2012-01-01

    The aim of this study was to reconstruct the evolutionary dynamics of the A(H1N1)pdm09 influenza virus in Italy during two epidemic seasons (2009/2010 and 2010/2011) in the light of the forces driving the evolution of the virus. Nearly six thousands respiratory specimens were collected from patients with influenza-like illness within the framework of the Italian Influenza Surveillance Network, and the A(H1N1)pdm09 hemagglutinin (HA) gene was amplified and directly sequenced from 227 of these. Phylodynamic and phylogeographical analyses were made using a Bayesian Markov Chain Monte Carlo method, and codon-specific positive selection acting on the HA coding sequence was evaluated. The global and local phylogenetic analyses showed that all of the Italian sequences sampled in the post-pandemic (2010/2011) season grouped into at least four highly significant Italian clades, whereas those of the pandemic season (2009/2010) were interspersed with isolates from other countries at the tree root. The time of the most recent common ancestor of the strains circulating in the pandemic season in Italy was estimated to be between the spring and summer of 2009, whereas the Italian clades of the post-pandemic season originated in the spring of 2010 and showed radiation in the summer/autumn of the same year; this was confirmed by a Bayesian skyline plot showing the biphasic growth of the effective number of infections. The local phylogeography analysis showed that the first season of infection originated in Northern Italian localities with high density populations, whereas the second involved less densely populated localities, in line with a gravity-like model of geographical dispersion. Two HA sites, codons 97 and 222, were under positive selection. In conclusion, the A(H1N1)pdm09 virus was introduced into Italy in the spring of 2009 by means of multiple importations. This was followed by repeated founder effects in the post-pandemic period that originated specific Italian clades

  4. In-Depth Analysis of HA and NS1 Genes in A(H1N1)pdm09 Infected Patients

    PubMed Central

    Caglioti, Claudia; Selleri, Marina; Rozera, Gabriella; Giombini, Emanuela; Zaccaro, Paola; Valli, Maria Beatrice; Capobianchi, Maria Rosaria

    2016-01-01

    In March/April 2009, a new pandemic influenza A virus (A(H1N1)pdm09) emerged and spread rapidly via human-to-human transmission, giving rise to the first pandemic of the 21th century. Influenza virus may be present in the infected host as a mixture of variants, referred to as quasi-species, on which natural and immune-driven selection operates. Since hemagglutinin (HA) and non-structural 1 (NS1) proteins are relevant in respect of adaptive and innate immune responses, the present study was aimed at establishing the intra-host genetic heterogeneity of HA and NS1 genes, applying ultra-deep pyrosequencing (UDPS) to nasopharyngeal swabs (NPS) from patients with confirmed influenza A(H1N1)pdm09 infection. The intra-patient nucleotide diversity of HA was significantly higher than that of NS1 (median (IQR): 37.9 (32.8–42.3) X 10−4 vs 30.6 (27.4–33.6) X 10−4 substitutions/site, p = 0.024); no significant correlation for nucleotide diversity of NS1 and HA was observed (r = 0.319, p = 0.29). Furthermore, a strong inverse correlation between nucleotide diversity of NS1 and viral load was observed (r = - 0.74, p = 0.004). For both HA and NS1, the variants appeared scattered along the genes, thus indicating no privileged mutation site. Known polymorphisms, S203T (HA) and I123V (NS1), were observed as dominant variants (>98%) in almost all patients; three HA and two NS1 further variants were observed at frequency >40%; a number of additional variants were detected at frequency <6% (minority variants), of which three HA and four NS1 variants were novel. In few patients multiple variants were observed at HA residues 203 and 222. According to the FLUSURVER tool, some of these variants may affect immune recognition and host range; however, these inferences are based on H5N1, and their extension to A(H1N1)pdm09 requires caution. More studies are necessary to address the significance of the composite nature of influenza virus quasi-species within infected patients. PMID

  5. In-Depth Analysis of HA and NS1 Genes in A(H1N1)pdm09 Infected Patients.

    PubMed

    Caglioti, Claudia; Selleri, Marina; Rozera, Gabriella; Giombini, Emanuela; Zaccaro, Paola; Valli, Maria Beatrice; Capobianchi, Maria Rosaria

    2016-01-01

    In March/April 2009, a new pandemic influenza A virus (A(H1N1)pdm09) emerged and spread rapidly via human-to-human transmission, giving rise to the first pandemic of the 21th century. Influenza virus may be present in the infected host as a mixture of variants, referred to as quasi-species, on which natural and immune-driven selection operates. Since hemagglutinin (HA) and non-structural 1 (NS1) proteins are relevant in respect of adaptive and innate immune responses, the present study was aimed at establishing the intra-host genetic heterogeneity of HA and NS1 genes, applying ultra-deep pyrosequencing (UDPS) to nasopharyngeal swabs (NPS) from patients with confirmed influenza A(H1N1)pdm09 infection. The intra-patient nucleotide diversity of HA was significantly higher than that of NS1 (median (IQR): 37.9 (32.8-42.3) X 10-4 vs 30.6 (27.4-33.6) X 10-4 substitutions/site, p = 0.024); no significant correlation for nucleotide diversity of NS1 and HA was observed (r = 0.319, p = 0.29). Furthermore, a strong inverse correlation between nucleotide diversity of NS1 and viral load was observed (r = - 0.74, p = 0.004). For both HA and NS1, the variants appeared scattered along the genes, thus indicating no privileged mutation site. Known polymorphisms, S203T (HA) and I123V (NS1), were observed as dominant variants (>98%) in almost all patients; three HA and two NS1 further variants were observed at frequency >40%; a number of additional variants were detected at frequency <6% (minority variants), of which three HA and four NS1 variants were novel. In few patients multiple variants were observed at HA residues 203 and 222. According to the FLUSURVER tool, some of these variants may affect immune recognition and host range; however, these inferences are based on H5N1, and their extension to A(H1N1)pdm09 requires caution. More studies are necessary to address the significance of the composite nature of influenza virus quasi-species within infected patients. PMID:27186639

  6. Beliefs and knowledge about vaccination against AH1N1pdm09 infection and uptake factors among Chinese parents.

    PubMed

    Wu, Cynthia Sau Ting; Kwong, Enid Wai Yung; Wong, Ho Ting; Lo, Suet Hang; Wong, Anthony Siu Wo

    2014-02-01

    Vaccination against AH1N1pdm09 infection (human swine infection, HSI) is an effective measure of preventing pandemic infection, especially for high-risk groups like children between the ages of 6 months and 6 years. This study used a cross-sectional correlation design and aimed to identify predicting factors of parental acceptance of the HSI vaccine (HSIV) and uptake of the vaccination by their preschool-aged children in Hong Kong. A total of 250 parents were recruited from four randomly selected kindergartens. A self-administered questionnaire based on the health belief framework was used for data collection. The results showed that a number of factors significantly affected the tendency toward new vaccination uptake; these factors included parental age, HSI vaccination history of the children in their family, preferable price of the vaccine, perceived severity, perceived benefits, perceived barriers, and motivating factors for taking new vaccines. Using these factors, a logistic regression model with a high Nagelkerke R2 of 0.63 was generated to explain vaccination acceptance. A strong correlation between parental acceptance of new vaccinations and the motivating factors of vaccination uptake was found, which indicates the importance of involving parents in policy implementation for any new vaccination schemes. Overall, in order to fight against pandemics and enhance vaccination acceptance, it is essential for the government to understand the above factors determining parental acceptance of new vaccinations for their preschool-aged children. PMID:24534766

  7. Structural Stability of Influenza A(H1N1)pdm09 Virus Hemagglutinins

    PubMed Central

    Yang, Hua; Chang, Jessie C.; Guo, Zhu; Carney, Paul J.; Shore, David A.; Donis, Ruben O.; Cox, Nancy J.; Villanueva, Julie M.; Klimov, Alexander I.

    2014-01-01

    ABSTRACT The noncovalent interactions that mediate trimerization of the influenza hemagglutinin (HA) are important determinants of its biological activities. Recent studies have demonstrated that mutations in the HA trimer interface affect the thermal and pH sensitivities of HA, suggesting a possible impact on vaccine stability (). We used size exclusion chromatography analysis of recombinant HA ectodomain to compare the differences among recombinant trimeric HA proteins from early 2009 pandemic H1N1 viruses, which dissociate to monomers, with those of more recent virus HAs that can be expressed as trimers. We analyzed differences among the HA sequences and identified intermolecular interactions mediated by the residue at position 374 (HA0 numbering) of the HA2 subdomain as critical for HA trimer stability. Crystallographic analyses of HA from the recent H1N1 virus A/Washington/5/2011 highlight the structural basis for this observed phenotype. It remains to be seen whether more recent viruses with this mutation will yield more stable vaccines in the future. IMPORTANCE Hemagglutinins from the early 2009 H1N1 pandemic viruses are unable to maintain a trimeric complex when expressed in a recombinant system. However, HAs from 2010 and 2011 strains are more stable, and our work highlights that the improvement in stability can be attributed to an E374K substitution in the HA2 subunit of the stalk that emerged naturally in the circulating viruses. PMID:24522930

  8. Whole genome characterization of human influenza A(H1N1)pdm09 viruses isolated from Kenya during the 2009 pandemic.

    PubMed

    Gachara, George; Symekher, Samuel; Otieno, Michael; Magana, Japheth; Opot, Benjamin; Bulimo, Wallace

    2016-06-01

    An influenza pandemic caused by a novel influenza virus A(H1N1)pdm09 spread worldwide in 2009 and is estimated to have caused between 151,700 and 575,400 deaths globally. While whole genome data on new virus enables a deeper insight in the pathogenesis, epidemiology, and drug sensitivities of the circulating viruses, there are relatively limited complete genetic sequences available for this virus from African countries. We describe herein the full genome analysis of influenza A(H1N1)pdm09 viruses isolated in Kenya between June 2009 and August 2010. A total of 40 influenza A(H1N1)pdm09 viruses isolated during the pandemic were selected. The segments from each isolate were amplified and directly sequenced. The resulting sequences of individual gene segments were concatenated and used for subsequent analysis. These were used to infer phylogenetic relationships and also to reconstruct the time of most recent ancestor, time of introduction into the country, rates of substitution and to estimate a time-resolved phylogeny. The Kenyan complete genome sequences clustered with globally distributed clade 2 and clade 7 sequences but local clade 2 viruses did not circulate beyond the introductory foci while clade 7 viruses disseminated country wide. The time of the most recent common ancestor was estimated between April and June 2009, and distinct clusters circulated during the pandemic. The complete genome had an estimated rate of nucleotide substitution of 4.9×10(-3) substitutions/site/year and greater diversity in surface expressed proteins was observed. We show that two clades of influenza A(H1N1)pdm09 virus were introduced into Kenya from the UK and the pandemic was sustained as a result of importations. Several closely related but distinct clusters co-circulated locally during the peak pandemic phase but only one cluster dominated in the late phase of the pandemic suggesting that it possessed greater adaptability. PMID:26921801

  9. Accumulation of Human-Adapting Mutations during Circulation of A(H1N1)pdm09 Influenza Virus in Humans in the United Kingdom

    PubMed Central

    Elderfield, Ruth A.; Watson, Simon J.; Godlee, Alexandra; Adamson, Walt E.; Thompson, Catherine I.; Dunning, Jake; Fernandez-Alonso, Mirian; Blumenkrantz, Deena; Hussell, Tracy; Zambon, Maria; Openshaw, Peter; Kellam, Paul

    2014-01-01

    ABSTRACT The influenza pandemic that emerged in 2009 provided an unprecedented opportunity to study adaptation of a virus recently acquired from an animal source during human transmission. In the United Kingdom, the novel virus spread in three temporally distinct waves between 2009 and 2011. Phylogenetic analysis of complete viral genomes showed that mutations accumulated over time. Second- and third-wave viruses replicated more rapidly in human airway epithelial (HAE) cells than did the first-wave virus. In infected mice, weight loss varied between viral isolates from the same wave but showed no distinct pattern with wave and did not correlate with viral load in the mouse lungs or severity of disease in the human donor. However, second- and third-wave viruses induced less alpha interferon in the infected mouse lungs. NS1 protein, an interferon antagonist, had accumulated several mutations in second- and third-wave viruses. Recombinant viruses with the third-wave NS gene induced less interferon in human cells, but this alone did not account for increased virus fitness in HAE cells. Mutations in HA and NA genes in third-wave viruses caused increased binding to α-2,6-sialic acid and enhanced infectivity in human mucus. A recombinant virus with these two segments replicated more efficiently in HAE cells. A mutation in PA (N321K) enhanced polymerase activity of third-wave viruses and also provided a replicative advantage in HAE cells. Therefore, multiple mutations allowed incremental changes in viral fitness, which together may have contributed to the apparent increase in severity of A(H1N1)pdm09 influenza virus during successive waves. IMPORTANCE Although most people infected with the 2009 pandemic influenza virus had mild or unapparent symptoms, some suffered severe and devastating disease. The reasons for this variability were unknown, but the numbers of severe cases increased during successive waves of human infection in the United Kingdom. To determine the causes

  10. Molecular characterization of the predominant influenza A(H1N1)pdm09 virus in Mexico, December 2011-February 2012.

    PubMed

    de la Rosa-Zamboni, Daniela; Vázquez-Pérez, Joel A; Avila-Ríos, Santiago; Carranco-Arenas, Ana Paola; Ormsby, Christopher E; Cummings, Craig A; Soto-Nava, Maribel; Hernández-Hernández, Víctor A; Orozco-Sánchez, Carmen O; la Barrera, Claudia Alvarado-de; Pérez-Padilla, Rogelio; Reyes-Terán, Gustavo

    2012-01-01

    When the A(H1N1)pdm09 pandemic influenza virus moved into the post-pandemic period, there was a worldwide predominance of the seasonal influenza A(H3N2) and B viruses. However, A(H1N1)pdm09 became the prevailing subtype in the 2011-2012 influenza season in Mexico and most of Central America. During this season, we collected nasopharyngeal swabs of individuals presenting with influenza-like illness at our institution in Mexico City. Samples were tested for seasonal A(H3N2) and B influenza viruses, as well as A(H1N1)pdm09 by real-time reverse transcription-polymerase chain reaction. Of 205 samples tested, 46% were positive to influenza, all of them A(H1N1)pdm09. The clinical characteristics of patients showed a similar pattern to the 2009 pandemic cases. Using next generation sequencing, we obtained whole genome sequences of viruses from 4 different patients, and in 8 additional viruses we performed partial Sanger sequencing of the HA segment. Non-synonymous changes found in the Mexican isolates with respect to the prototype isolate H1N1 (A/California/04/2009) included HA S69T, K163R and N260D unique to 2012 Mexican and North American isolates and located within or adjacent to HA antigenic sites; HA S143G, S185T, A197T and S203T previously reported in viruses from the 2010-2011 season, located within or adjacent to HA antigenic sites; and HA E374K located in a relevant site for membrane fusion. All Mexican isolates had an oseltamivir-sensitive genotype. Phylogenetic analysis with all 8 influenza gene segments showed that 2012 Mexican sequences formed a robust, distinct cluster. In all cases, 2012 Mexican sequences tended to group with 2010-2011 Asian and European sequences, but not with 2009 Mexican sequences, suggesting a possible recent common ancestor between these latter regions and the 2012 Mexican viruses. It remains to be defined if these viral changes represent an important antigenic drift that would enable viral immune evasion and/or affect influenza vaccine

  11. Transmission of the First Influenza A(H1N1)pdm09 Pandemic Wave in Australia Was Driven by Undetected Infections: Pandemic Response Implications

    PubMed Central

    Fielding, James E.; Kelly, Heath A.; Glass, Kathryn

    2015-01-01

    Background During the first wave of influenza A(H1N1)pdm09 in Victoria, Australia the rapid increase in notified cases and the high proportion with relatively mild symptoms suggested that community transmission was established before cases were identified. This lead to the hypothesis that those with low-level infections were the main drivers of the pandemic. Methods A deterministic susceptible-infected-recovered model was constructed to describe the first pandemic wave in a population structured by disease severity levels of asymptomatic, low-level symptoms, moderate symptoms and severe symptoms requiring hospitalisation. The model incorporated mixing, infectivity and duration of infectiousness parameters to calculate subgroup-specific reproduction numbers for each severity level. Results With stratum-specific effective reproduction numbers of 1.82 and 1.32 respectively, those with low-level symptoms, and those with asymptomatic infections were responsible for most of the transmission. The effective reproduction numbers for infections resulting in moderate symptoms and hospitalisation were less than one. Sensitivity analyses confirmed the importance of parameters relating to asymptomatic individuals and those with low-level symptoms. Conclusions Transmission of influenza A(H1N1)pdm09 was largely driven by those invisible to the health system. This has implications for control measures–such as distribution of antivirals to cases and contacts and quarantine/isolation–that rely on detection of infected cases. Pandemic plans need to incorporate milder scenarios, with a graded approach to implementation of control measures. PMID:26692335

  12. Molecular genetic analysis of the Influenza A(H1N1)pdm09 virus from lethal and recovered cases in Russia from 2009 to 2014: Deletions in the nucleoprotein.

    PubMed

    Yatsyshina, Svetlana; Renteeva, Anna; Deviatkin, Andrei; Vorobyeva, Nadezhda; Minenko, Angrey; Valdokhina, Anna; Elkina, Mariya; Kuleshov, Konstantin; Shipulin, German

    2015-08-01

    Influenza A(H1N1)pdm09 virus caused about 2000 laboratory confirmed lethal cases in Russia during 2009-2010 and 1302, 135 and 29 cases in the 2010-2011, 2012-2013 and 2013-2014 seasons respectively. The on average short duration (7.8±5 days) of lethal cases of Influenza A(H1N1)pdm09 infections in Russia suggests primary viral rather than secondary bacterial pneumonia. Hemorrhagic syndrome was recorded in 36.6% of patients. An examination of 221 lung samples from lethal influenza cases for the presence of bacterial DNA that could cause pneumonia did not reveal bacterial superinfections in 86% of cases. Molecular-genetic analyses of Influenza A(H1N1)pdm09 viruses from lethal and recovered cases were performed. Amino acids G and N at position 222 of the influenza virus hemagglutinin, which increase the affinity for the lower respiratory tract receptors, were detected more often in the lungs of patients who died than in respiratory swabs collected from recovered patients (p<0.0001 and p=0.007). Viruses harboring various mutations (222D/G/N/S) was significantly associated with lung samples compared with respiratory swabs from recovered patients (p<0.0001). Amino acid 222E, which increases the affinity for upper respiratory tract receptors, was found more frequently in recovered patients than in patients with lethal disease (27% versus 3%, p=0.005). Phylogenetic analysis identified an isolated cluster of viruses in the 2009-2010 season that harbored amino acid 222E, which could explain the high transmissibility of the virus at the beginning of the pandemic. Bayesian skyline plot implied a decline in the effective population size of Influenza A(H1N1)pdm09 viruses in Russia from 2010-2011 to 2011-2012, followed by an increase in 2012-2013; this trend was accompanied by the increased genetic diversity of the hemagglutinin antigenic sites. Mutations of viral RNA leading to oseltamivir resistance were found in 2.8% of tested patients during only 2010-2011 season. Deletions

  13. Antigenic and genomic characterization of human influenza A and B viruses circulating in Argentina after the introduction of influenza A(H1N1)pdm09.

    PubMed

    Russo, Mara L; Pontoriero, Andrea V; Benedetti, Estefania; Czech, Andrea; Avaro, Martin; Periolo, Natalia; Campos, Ana M; Savy, Vilma L; Baumeister, Elsa G

    2014-12-01

    This study was conducted as part of the Argentinean Influenza and other Respiratory Viruses Surveillance Network, in the context of the Global Influenza Surveillance carried out by the World Health Organization (WHO). The objective was to study the activity and the antigenic and genomic characteristics of circulating viruses for three consecutive seasons (2010, 2011 and 2012) in order to investigate the emergence of influenza viral variants. During the study period, influenza virus circulation was detected from January to December. Influenza A and B, and all current subtypes of human influenza viruses, were present each year. Throughout the 2010 post-pandemic season, influenza A(H1N1)pdm09, unexpectedly, almost disappeared. The haemagglutinin (HA) of the A(H1N1)pdm09 viruses studied were segregated in a different genetic group to those identified during the 2009 pandemic, although they were still antigenically closely related to the vaccine strain A/California/07/2009. Influenza A(H3N2) viruses were the predominant strains circulating during the 2011 season, accounting for nearly 76 % of influenza viruses identified. That year, all HA sequences of the A(H3N2) viruses tested fell into the A/Victoria/208/2009 genetic clade, but remained antigenically related to A/Perth/16/2009 (reference vaccine recommended for this three-year period). A(H3N2) viruses isolated in 2012 were antigenically closely related to A/Victoria/361/2011, recommended by the WHO as the H3 component for the 2013 Southern Hemisphere formulation. B viruses belonging to the B/Victoria lineage circulated in 2010. A mixed circulation of viral variants of both B/Victoria and B/Yamagata lineages was detected in 2012, with the former being predominant. A(H1N1)pdm09 viruses remained antigenically closely related to the vaccine virus A/California/7/2009; A(H3N2) viruses continually evolved into new antigenic clusters and both B lineages, B/Victoria/2/87-like and B/Yamagata/16/88-like viruses, were observed

  14. The Comparative Clinical Course of Pregnant and Non-Pregnant Women Hospitalised with Influenza A(H1N1)pdm09 Infection

    PubMed Central

    Brett, Stephen J.; Enstone, Joanne E.; Read, Robert C.; Openshaw, Peter J. M.; Semple, Malcolm G.; Lim, Wei Shen; Taylor, Bruce L.; McMenamin, James; Nicholson, Karl G.; Bannister, Barbara; Nguyen-Van-Tam, Jonathan S.

    2012-01-01

    Introduction The Influenza Clinical Information Network (FLU-CIN) was established to gather detailed clinical and epidemiological information about patients with laboratory confirmed A(H1N1)pdm09 infection in UK hospitals. This report focuses on the clinical course and outcomes of infection in pregnancy. Methods A standardised data extraction form was used to obtain detailed clinical information from hospital case notes and electronic records, for patients with PCR-confirmed A(H1N1)pdm09 infection admitted to 13 sentinel hospitals in five clinical 'hubs' and a further 62 non-sentinel hospitals, between 11th May 2009 and 31st January 2010.Outcomes were compared for pregnant and non-pregnant women aged 15–44 years, using univariate and multivariable techniques. Results Of the 395 women aged 15–44 years, 82 (21%) were pregnant; 73 (89%) in the second or third trimester. Pregnant women were significantly less likely to exhibit severe respiratory distress at initial assessment (OR = 0.49 (95% CI: 0.30–0.82)), require supplemental oxygen on admission (OR = 0.40 (95% CI: 0.20–0.80)), or have underlying co-morbidities (p-trend <0.001). However, they were equally likely to be admitted to high dependency (Level 2) or intensive care (Level 3) and/or to die, after adjustment for potential confounders (adj. OR = 0.93 (95% CI: 0.46–1.92). Of 11 pregnant women needing Level 2/3 care, 10 required mechanical ventilation and three died. Conclusions Since the expected prevalence of pregnancy in the source population was 6%, our data suggest that pregnancy greatly increased the likelihood of hospital admission with A(H1N1)pdm09. Pregnant women were less likely than non-pregnant women to have respiratory distress on admission, but severe outcomes were equally likely in both groups. PMID:22870239

  15. Serologic evidence of influenza A(H1N1)pdm09 virus in northern sea otters

    USGS Publications Warehouse

    Li, Zhu-Nan; Ip, Hon S.; Frost, Jessica F.; White, C. LeAnn; Murray, Michael J.; Carney, Paul J.; Sun, Xiang-Jie; Stevens, James; Levine, Min Z.; Katz, Jacqueline M.

    2014-01-01

    Sporadic epizootics of pneumonia among marine mammals have been associated with multiple animal-origin influenza A virus subtypes (1–6); seals are the only known nonhuman host for influenza B viruses (7). Recently, we reported serologic evidence of influenza A virus infection in free-ranging northern sea otters (Enhydra lutris kenyoni) captured off the coast of Washington, USA, in August 2011 (8). To investigate further which influenza A virus subtype infected these otters, we tested serum samples from these otters by ELISA for antibody-binding activity against 12 recombinant hemagglutinins (rHAs) from 7 influenza A hemagglutinin (HA) subtypes and 2 lineages of influenza B virus (Technical Appendix Table 1). Estimated ages for the otters were 2–19 years (Technical Appendix Table 2); we also tested archived serum samples from sea otters of similar ages collected from a study conducted during 2001–2002 along the Washington coast (9).

  16. Rapid spread of influenza A(H1N1)pdm09 viruses with a new set of specific mutations in the internal genes in the beginning of 2015/2016 epidemic season in Moscow and Saint Petersburg (Russian Federation).

    PubMed

    Komissarov, Andrey; Fadeev, Artem; Sergeeva, Maria; Petrov, Sergey; Sintsova, Kseniya; Egorova, Anna; Pisareva, Maria; Buzitskaya, Zhanna; Musaeva, Tamila; Danilenko, Daria; Konovalova, Nadezhda; Petrova, Polina; Stolyarov, Kirill; Smorodintseva, Elizaveta; Burtseva, Elena; Krasnoslobodtsev, Kirill; Kirillova, Elena; Karpova, Lyudmila; Eropkin, Mikhail; Sominina, Anna; Grudinin, Mikhail

    2016-07-01

    A dramatic increase of influenza activity in Russia since week 3 of 2016 significantly differs from previous seasons in terms of the incidence of influenza and acute respiratory infection (ARI) and in number of lethal cases. We performed antigenic analysis of 108 and whole-genome sequencing of 77 influenza A(H1N1)pdm09 viruses from Moscow and Saint Petersburg. Most of the viruses were antigenically related to the vaccine strain. Whole-genome analysis revealed a composition of specific mutations in the internal genes (D2E and M83I in NEP, E125D in NS1, M105T in NP, Q208K in M1, and N204S in PA-X) that probably emerged before the beginning of 2015/2016 epidemic season. PMID:26992820

  17. Predominance of HA-222D/G Polymorphism in Influenza A(H1N1)pdm09 Viruses Associated with Fatal and Severe Outcomes Recently Circulating in Germany

    PubMed Central

    Wedde, Marianne; Wählisch, Stephanie; Wolff, Thorsten; Schweiger, Brunhilde

    2013-01-01

    Influenza A(H1N1)pdm09 viruses cause sporadically very severe disease including fatal clinical outcomes associated with pneumonia, viremia and myocarditis. A mutation characterized by the substitution of aspartic acid (wild-type) to glycine at position 222 within the haemagglutinin gene (HA-D222G) was recorded during the 2009 H1N1 pandemic in Germany and other countries with significant frequency in fatal and severe cases. Additionally, A(H1N1)pdm09 viruses exhibiting the polymorphism HA-222D/G/N were detected both in the respiratory tract and in blood. Specimens from mild, fatal and severe cases were collected to study the heterogeneity of HA-222 in A(H1N1)pdm09 viruses circulating in Germany between 2009 and 2011. In order to enable rapid and large scale analysis we designed a pyrosequencing (PSQ) assay. In 2009/2010, the 222D wild-type of A(H1N1)pdm09 viruses predominated in fatal and severe outcomes. Moreover, co-circulating virus mutants exhibiting a D222G or D222E substitution (8/6%) as well as HA-222 quasispecies were identified (10%). Both the 222D/G and the 222D/G/N/V/Y polymorphisms were confirmed by TA cloning. PSQ analyses of viruses associated with mild outcomes revealed mainly the wild-type 222D and no D222G change in both seasons. However, an increase of variants with 222D/G polymorphism (60%) was characteristic for A(H1N1)pdm09 viruses causing fatal and severe cases in the season 2010/2011. Pure 222G viruses were not observed. Our results support the hypothesis that the D222G change may result from adaptation of viral receptor specificity to the lower respiratory tract. This could explain why transmission of the 222G variant is less frequent among humans. Thus, amino acid changes at HA position 222 may be the result of viral intra-host evolution leading to the generation of variants with an altered viral tropism. PMID:23451145

  18. Nosocomial Co-Transmission of Avian Influenza A(H7N9) and A(H1N1)pdm09 Viruses between 2 Patients with Hematologic Disorders.

    PubMed

    Chen, Huazhong; Liu, Shelan; Liu, Jun; Chai, Chengliang; Mao, Haiyan; Yu, Zhao; Tang, Yuming; Zhu, Geqin; Chen, Haixiao X; Zhu, Chengchu; Shao, Hui; Tan, Shuguang; Wang, Qianli; Bi, Yuhai; Zou, Zhen; Liu, Guang; Jin, Tao; Jiang, Chengyu; Gao, George F; Peiris, Malik; Yu, Hongjie; Chen, Enfu

    2016-04-01

    A nosocomial cluster induced by co-infections with avian influenza A(H7N9) and A(H1N1)pdm09 (pH1N1) viruses occurred in 2 patients at a hospital in Zhejiang Province, China, in January 2014. The index case-patient was a 57-year-old man with chronic lymphocytic leukemia who had been occupationally exposed to poultry. He had co-infection with H7N9 and pH1N1 viruses. A 71-year-old man with polycythemia vera who was in the same ward as the index case-patient for 6 days acquired infection with H7N9 and pH1N1 viruses. The incubation period for the second case-patient was estimated to be <4 days. Both case-patients died of multiple organ failure. Virus genetic sequences from the 2 case-patients were identical. Of 103 close contacts, none had acute respiratory symptoms; all were negative for H7N9 virus. Serum samples from both case-patients demonstrated strong proinflammatory cytokine secretion but incompetent protective immune responses. These findings strongly suggest limited nosocomial co-transmission of H7N9 and pH1N1 viruses from 1 immunocompromised patient to another. PMID:26982379

  19. Nosocomial Co-Transmission of Avian Influenza A(H7N9) and A(H1N1)pdm09 Viruses between 2 Patients with Hematologic Disorders

    PubMed Central

    Chen, Huazhong; Liu, Shelan; Liu, Jun; Chai, Chengliang; Mao, Haiyan; Yu, Zhao; Tang, Yuming; Zhu, Geqin; Chen, Haixiao X.; Zhu, Chengchu; Shao, Hui; Tan, Shuguang; Wang, Qianli; Bi, Yuhai; Zou, Zhen; Liu, Guang; Jin, Tao; Jiang, Chengyu; Gao, George F.; Peiris, Malik

    2016-01-01

    A nosocomial cluster induced by co-infections with avian influenza A(H7N9) and A(H1N1)pdm09 (pH1N1) viruses occurred in 2 patients at a hospital in Zhejiang Province, China, in January 2014. The index case-patient was a 57-year-old man with chronic lymphocytic leukemia who had been occupationally exposed to poultry. He had co-infection with H7N9 and pH1N1 viruses. A 71-year-old man with polycythemia vera who was in the same ward as the index case-patient for 6 days acquired infection with H7N9 and pH1N1 viruses. The incubation period for the second case-patient was estimated to be <4 days. Both case-patients died of multiple organ failure. Virus genetic sequences from the 2 case-patients were identical. Of 103 close contacts, none had acute respiratory symptoms; all were negative for H7N9 virus. Serum samples from both case-patients demonstrated strong proinflammatory cytokine secretion but incompetent protective immune responses. These findings strongly suggest limited nosocomial co-transmission of H7N9 and pH1N1 viruses from 1 immunocompromised patient to another. PMID:26982379

  20. Predominance of influenza A(H1N1)pdm09 virus genetic subclade 6B.1 and influenza B/Victoria lineage viruses at the start of the 2015/16 influenza season in Europe.

    PubMed

    Broberg, Eeva; Melidou, Angeliki; Prosenc, Katarina; Bragstad, Karoline; Hungnes, Olav

    2016-03-31

    Influenza A(H1N1)pdm09 viruses predominated in the European influenza 2015/16 season. Most analysed viruses clustered in a new genetic subclade 6B.1, antigenically similar to the northern hemisphere vaccine component A/California/7/2009. The predominant influenza B lineage was Victoria compared with Yamagata in the previous season. It remains to be evaluated at the end of the season if these changes affected the effectiveness of the vaccine for the 2015/16 season. PMID:27074657

  1. Influenza A(H1N1)pdm09 virus exhibiting enhanced cross-resistance to oseltamivir and peramivir due to a dual H275Y/G147R substitution, Japan, March 2016.

    PubMed

    Takashita, Emi; Fujisaki, Seiichiro; Shirakura, Masayuki; Nakamura, Kazuya; Kishida, Noriko; Kuwahara, Tomoko; Shimazu, Yukie; Shimomura, Takeshi; Watanabe, Shinji; Odagiri, Takato

    2016-06-16

    An influenza A(H1N1)pdm09 virus carrying a G147R substitution in combination with an H275Y substitution in the neuraminidase protein, which confers cross-resistance to oseltamivir and peramivir, was detected from an immunocompromised inpatient in Japan, March 2016. This dual H275Y/G147R mutant virus exhibited enhanced cross-resistance to both drugs compared with the single H275Y mutant virus and reduced susceptibility to zanamivir, although it showed normal inhibition by laninamivir. PMID:27336226

  2. Impact of Potential Permissive Neuraminidase Mutations on Viral Fitness of the H275Y Oseltamivir-Resistant Influenza A(H1N1)pdm09 Virus In Vitro, in Mice and in Ferrets

    PubMed Central

    Abed, Yacine; Pizzorno, Andrés; Bouhy, Xavier; Rhéaume, Chantal

    2014-01-01

    Neuraminidase (NA) mutations conferring resistance to NA inhibitors (NAIs) generally compromise the fitness of influenza viruses. The only NAI-resistant virus that widely spread in the population, the A/Brisbane/59/2007 (H1N1) strain, contained permissive mutations that restored the detrimental effect caused by the H275Y change. Computational analysis predicted other permissive NA mutations for A(H1N1)pdm09 viruses. Here, we investigated the effect of T289M and N369K mutations on the viral fitness of the A(H1N1)pdm09 H275Y variant. Recombinant wild-type (WT) A(H1N1)pdm09 and the H275Y, H275Y/T289M, H275Y/N369K, and H275Y/V241I/N369K (a natural variant) NA mutants were generated by reverse genetics. Replication kinetics were performed by using ST6GalI-MDCK cells. Virulence was assessed in C57BL/6 mice, and contact transmission was evaluated in ferrets. The H275Y mutation significantly reduced viral titers during the first 12 to 36 h postinfection (p.i.) in vitro. Nevertheless, the WT and H275Y viruses induced comparable mortality rates, weight loss, and lung titers in mice. The T289M mutation eliminated the detrimental effect caused by the H275Y change in vitro while causing greater weight loss and mortality in mice, with significantly higher lung viral titers on days 3 and 6 p.i. than with the H275Y mutant. In index ferrets, the WT, H275Y, H275Y/T289M, and H275Y/V241I/N369K recombinants induced comparable fever, weight loss, and nasal wash viral titers. All tested viruses were transmitted at comparable rates in contact ferrets, with the H275Y/V241I/N369K recombinant demonstrating higher nasal wash viral titers than the H275Y mutant. Permissive mutations may enhance the fitness of A(H1N1)pdm09 H275Y viruses in vitro and in vivo. The emergence of such variants should be carefully monitored. PMID:24257597

  3. Rapid research response to the 2009 A(H1N1)pdm09 influenza pandemic (Revised)

    PubMed Central

    2013-01-01

    Background When novel influenza viruses cause human infections, it is critical to characterize the illnesses, viruses, and immune responses to infection in order to develop diagnostics, treatments, and vaccines. The objective of the study was to collect samples from patients with suspected or confirmed A(H1N1)pdm09 infections that could be made available to the scientific community. Respiratory secretions, sera and peripheral blood mononuclear cells (PBMCs) were collected sequentially (when possible) from patients presenting with suspected or previously confirmed A(H1N1)pdm09 infections. Clinical manifestations and illness outcomes were assessed. Respiratory secretions were tested for the presence of A(H1N1)pdm09 virus by means of isolation in tissue culture and real time RT-PCR. Sera were tested for the presence and level of HAI and neutralizing antibodies against the A(H1N1)pdm09 virus. Findings and conclusions Thirty patients with confirmed A(H1N1)pdm09 infection were enrolled at Baylor College of Medicine (BCM). Clinical manifestations of illness were consistent with typical influenza. Twenty-eight of 30 had virological confirmation of illness; all recovered fully. Most patients had serum antibody responses or high levels of antibody in convalescent samples. Virus-positive samples were sent to J. Craig Venter Institute for sequencing and sequences were deposited in GenBank. Large volumes of sera collected from 2 convalescent adults were used to standardize antibody assays; aliquots of these sera are available from the repository. Aliquots of serum, PBMCs and stool collected from BCM subjects and subjects enrolled at other study sites are available for use by the scientific community, upon request. PMID:23641940

  4. Hospitalization Risk Due to Respiratory Illness Associated with Genetic Variation at IFITM3 in Patients with Influenza A(H1N1)pdm09 Infection: A Case-Control Study

    PubMed Central

    Gaio, Vânia; Nunes, Baltazar; Pechirra, Pedro; Conde, Patrícia; Guiomar, Raquel; Dias, Carlos Matias

    2016-01-01

    Background Recent studies suggest an association between the Interferon Inducible Transmembrane 3 (IFITM3) rs12252 variant and the course of influenza infection. However, it is not clear whether the reported association relates to influenza infection severity. The aim of this study was to estimate the hospitalization risk associated with this variant in Influenza Like Illness (ILI) patients during the H1N1 pandemic influenza. Methods A case-control genetic association study was performed, using nasopharyngeal/oropharyngeal swabs collected during the H1N1 pandemic influenza. Laboratory diagnosis of influenza infection was performed by RT-PCR, the IFITM3 rs12252 was genotyped by RFLP and tested for association with hospitalization. Conditional logistic regression was performed to calculate the confounder-adjusted odds ratio of hospitalization associated with IFITM3 rs12252. Results We selected 312 ILI cases and 624 matched non-hospitalized controls. Within ILI Influenza A(H1N1)pdm09 positive patients, no statistical significant association was found between the variant and the hospitalization risk (Adjusted OR: 0.73 (95%CI: 0.33–1.50)). Regarding ILI Influenza A(H1N1)pdm09 negative patients, CT/CC genotype carriers had a higher risk of being hospitalized than patients with TT genotype (Adjusted OR: 2.54 (95%CI: 1.54–4.19)). Conclusions The IFITM3 rs12252 variant was associated with respiratory infection hospitalization but not specifically in patients infected with Influenza A(H1N1)pdm09. PMID:27351739

  5. Clinical effectiveness of neuraminidase inhibitors--oseltamivir, zanamivir, laninamivir, and peramivir--for treatment of influenza A(H3N2) and A(H1N1)pdm09 infection: an observational study in the 2010-2011 influenza season in Japan.

    PubMed

    Shobugawa, Yugo; Saito, Reiko; Sato, Isamu; Kawashima, Takashi; Dapat, Clyde; Dapat, Isolde Caperig; Kondo, Hiroki; Suzuki, Yasushi; Saito, Kousuke; Suzuki, Hiroshi

    2012-12-01

    The clinical effectiveness of the newly released neuraminidase inhibitors (NAIs) laninamivir and peramivir has not been sufficiently evaluated in influenza-infected patients in clinical and practical settings. In this study, we analyzed the clinical data of 211 patients infected with influenza A virus subtype H3N2 (A(H3N2)) and 45 patients infected with influenza A virus subtype H1N1pdm (A(H1N1)pdm09) who received the NAIs oseltamivir, zanamivir, laninamivir, or peramivir during the 2010-2011 influenza season. The duration of fever from the first dose of the NAI to fever alleviation to <37.5 °C was evaluated as an indicator of the clinical effectiveness of the NAIs in the influenza-infected patients. For the A(H3N2)-infected patients, Kaplan-Meier analysis showed the peramivir treatment group had the fastest time of fever alleviation to <37.5 °C (median 17.0 h, 95 % confidence interval [CI] 7.2-26.8 h) of the four treatment groups. No significant difference was found in the time to fever alleviation among the other antivirals, oseltamivir, zanamivir, and laninamivir. Results of multivariate analysis, using a Cox proportional-hazards model (hazard ratio 3.321) adjusted for the factors age, sex, body weight, vaccination status, time from onset to the clinic visit, and body temperature showed significantly faster fever alleviation in the peramivir treatment group compared with the oseltamivir treatment group. For the A(H1N1)pdm09-infected patients, only the oseltamivir and zanamivir treatment groups were compared, and no significant difference in time to alleviation of fever was observed between the two groups. Based on a cycling probe real-time polymerase chain reaction (PCR) assay, none of the A(H1N1)pdm09 strains in this study had the H275Y mutation conferring oseltamivir resistance. Further evaluation of the clinical effectiveness of the newly released NAIs for influenza-infected patients, including those infected with A(H1N1)pdm09, is needed. PMID:22644080

  6. Detection of pandemic strain of influenza virus (A/H1N1/pdm09) in pigs, West Africa: implications and considerations for prevention of future influenza pandemics at the source

    PubMed Central

    Adeola, Oluwagbenga A.; Olugasa, Babasola O.; Emikpe, Benjamin O.

    2015-01-01

    Background Human and animal influenza are inextricably linked. In particular, the pig is uniquely important as a mixing vessel for genetic reassortment of influenza viruses, leading to emergence of novel strains which may cause human pandemics. Significant reduction in transmission of influenza viruses from humans, and other animals, to swine may therefore be crucial for preventing future influenza pandemics. This study investigated the presence of the 2009 pandemic influenza A/H1N1 virus, A(H1N1)pdm09, in Nigerian and Ghanaian pigs, and also determined levels of acceptance of preventive measures which could significantly reduce the transmission of this virus from humans to pigs. Methods Nasal swab specimens from 125 pigs in Ibadan, Nigeria, and Kumasi, Ghana, were tested for the presence of influenza A/California/04/2009 (H1N1) by quantitative antigen-detection ELISA. A semi-structured questionnaire was also administered to pig handlers in the two study areas and responses were analyzed to evaluate their compliance with seven measures for preventing human-to-swine transmission of influenza viruses. Results The virus was detected among pigs in the two cities, with prevalence of 8% in Ibadan and 10% in Kumasi. Levels of compliance of pig handlers with relevant preventive measures were also found to be mostly below 25 and 40% in Ibadan and Kumasi, respectively. Conclusion Detection of influenza A(H1N1)pdm09 among pigs tested suggests the possibility of human-to-swine transmission, which may proceed even more rapidly, considering the very poor acceptance of basic preventive measures observed in this study. This is also the first report on detection of influenza A(H1N1)pdm09 in Ghanaian pigs. We recommend improvement on personal hygiene among pig handlers, enforcement of sick leave particularly during the first few days of influenza-like illnesses, and training of pig handlers on recognition of influenza-like signs in humans and pigs. These could be crucial for

  7. Live attenuated influenza A virus vaccine protects against heterologous challenge with A(H1N1)pdm09 without inducing vaccine associated enhanced respiratory disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Influenza A virus (IAV) vaccines that provide broad cross-protection against antigenic variants are necessary to prevent infection and shedding of the wide array of IAV cocirculating in swine. Whole inactivated virus (WIV) vaccines provide only partial protection against IAV with substantial antigen...

  8. Live attenuated influenza A virus vaccine protects against A(H1N1)pdm09 heterologous challenge without vaccine associated enhanced respiratory disease.

    PubMed

    Gauger, Phillip C; Loving, Crystal L; Khurana, Surender; Lorusso, Alessio; Perez, Daniel R; Kehrli, Marcus E; Roth, James A; Golding, Hana; Vincent, Amy L

    2014-12-01

    Live-attenuated influenza virus (LAIV) vaccines may provide cross-protection against contemporary influenza A virus (IAV) in swine. Conversely, whole inactivated virus (WIV) vaccines have the potential risk of vaccine-associated enhanced respiratory disease (VAERD) when challenged with IAV of substantial antigenic drift. A temperature sensitive, intranasal H1N2 LAIV was compared to wild type exposure (WT) and an intramuscular WIV vaccine in a model shown to induce VAERD. WIV vaccinated swine challenged with pandemic A/H1N1 (H1N1pdm09) were not protected from infection and demonstrated severe respiratory disease consistent with VAERD. Lung lesions were mild and challenge virus was not detected in the respiratory tract of LAIV vaccinates. High levels of post-vaccination IgG serum antibodies targeting the H1N1pdm09 HA2 stalk domain were exclusively detected in the WIV group and associated with increased H1N1pdm09 virus infectivity in MDCK cells. In contrast, infection-enhancing antibodies were not detected in the serum of LAIV vaccinates and VAERD was not observed. PMID:25461535

  9. International Laboratory Comparison of Influenza Microneutralization Assays for A(H1N1)pdm09, A(H3N2), and A(H5N1) Influenza Viruses by CONSISE.

    PubMed

    Laurie, Karen L; Engelhardt, Othmar G; Wood, John; Heath, Alan; Katz, Jacqueline M; Peiris, Malik; Hoschler, Katja; Hungnes, Olav; Zhang, Wenqing; Van Kerkhove, Maria D

    2015-08-01

    The microneutralization assay is commonly used to detect antibodies to influenza virus, and multiple protocols are used worldwide. These protocols differ in the incubation time of the assay as well as in the order of specific steps, and even within protocols there are often further adjustments in individual laboratories. The impact these protocol variations have on influenza serology data is unclear. Thus, a laboratory comparison of the 2-day enzyme-linked immunosorbent assay (ELISA) and 3-day hemagglutination (HA) microneutralization (MN) protocols, using A(H1N1)pdm09, A(H3N2), and A(H5N1) viruses, was performed by the CONSISE Laboratory Working Group. Individual laboratories performed both assay protocols, on multiple occasions, using different serum panels. Thirteen laboratories from around the world participated. Within each laboratory, serum sample titers for the different assay protocols were compared between assays to determine the sensitivity of each assay and were compared between replicates to assess the reproducibility of each protocol for each laboratory. There was good correlation of the results obtained using the two assay protocols in most laboratories, indicating that these assays may be interchangeable for detecting antibodies to the influenza A viruses included in this study. Importantly, participating laboratories have aligned their methodologies to the CONSISE consensus 2-day ELISA and 3-day HA MN assay protocols to enable better correlation of these assays in the future. PMID:26108286

  10. International Laboratory Comparison of Influenza Microneutralization Assays for A(H1N1)pdm09, A(H3N2), and A(H5N1) Influenza Viruses by CONSISE

    PubMed Central

    Engelhardt, Othmar G.; Wood, John; Heath, Alan; Katz, Jacqueline M.; Peiris, Malik; Hoschler, Katja; Hungnes, Olav; Zhang, Wenqing; Van Kerkhove, Maria D.

    2015-01-01

    The microneutralization assay is commonly used to detect antibodies to influenza virus, and multiple protocols are used worldwide. These protocols differ in the incubation time of the assay as well as in the order of specific steps, and even within protocols there are often further adjustments in individual laboratories. The impact these protocol variations have on influenza serology data is unclear. Thus, a laboratory comparison of the 2-day enzyme-linked immunosorbent assay (ELISA) and 3-day hemagglutination (HA) microneutralization (MN) protocols, using A(H1N1)pdm09, A(H3N2), and A(H5N1) viruses, was performed by the CONSISE Laboratory Working Group. Individual laboratories performed both assay protocols, on multiple occasions, using different serum panels. Thirteen laboratories from around the world participated. Within each laboratory, serum sample titers for the different assay protocols were compared between assays to determine the sensitivity of each assay and were compared between replicates to assess the reproducibility of each protocol for each laboratory. There was good correlation of the results obtained using the two assay protocols in most laboratories, indicating that these assays may be interchangeable for detecting antibodies to the influenza A viruses included in this study. Importantly, participating laboratories have aligned their methodologies to the CONSISE consensus 2-day ELISA and 3-day HA MN assay protocols to enable better correlation of these assays in the future. PMID:26108286

  11. Characteristic amino acid changes of influenza A(H1N1)pdm09 virus PA protein enhance A(H7N9) viral polymerase activity.

    PubMed

    Liu, Jun; Huang, Feng; Zhang, Junsong; Tan, Likai; Lu, Gen; Zhang, Xu; Zhang, Hui

    2016-06-01

    Human coinfection with a novel H7N9 influenza virus and the 2009 pandemic A(H1N1) influenza virus, H1N1pdm09, has recently been reported in China. Because reassortment can occur during coinfection, it is necessary to clarify the effects of gene reassortment between these two viruses. Among the viral ribonucleoprotein complex (vRNP) genes, only the PA gene of H1N1pdm09 enhances the avian influenza viral polymerase activity. Based on a phylogenetic analysis, we show a special evolutionary feature of the H1N1pdm09 PA gene, which clustered with those of the novel H7N9 virus and related H9N2 viruses, rather than in the outgroup as the H1N1pdm09 genes do on the phylogenetic trees of other vRNP genes. Using a minigenome system of the novel H7N9 virus, we further demonstrate that replacement of its PA gene significantly enhanced its polymerase activity, whereas replacement of the other vRNP genes reduced its polymerase activity. We also show that the residues of PA evolutionarily conserved between H1N1pdm09 and the novel H7N9 virus are associated with attenuated or neutral polymerase activity. The mutations associated with the increased activity of the novel H7N9 polymerase are characteristic of the H1N1pdm09 gene, and are located almost adjacent to the surface of the PA protein. Our results suggest that the novel H7N9 virus has more effective PB1, PB2, and NP genes than H1N1pdm09, and that H1N1pdm09-like PA mutations enhance the novel H7N9 polymerase function. PMID:26980671

  12. Host Adaptation and the Alteration of Viral Properties of the First Influenza A/H1N1pdm09 Virus Isolated in Japan

    PubMed Central

    Ainai, Akira; Hasegawa, Hideki; Obuchi, Masatsugu; Odagiri, Takato; Ujike, Makoto; Shirakura, Masayuki; Nobusawa, Eri; Tashiro, Masato; Asanuma, Hideki

    2015-01-01

    A/Narita/1/2009 (A/N) was the first H1N1 virus from the 2009 pandemic (H1pdm) to be isolated in Japan. To better understand and predict the possible development of this virus strain, the effect of passaging A/N was investigated in Madin-Darby canine kidney cells, chicken eggs and mice. A/N that had been continuously passaged in cells, eggs, or mice obtained the ability to grow efficiently in each host. Moreover, A/N grown in mice had both a high level of pathogenicity in mice and an increased growth rate in cells and eggs. Changes in growth and pathogenicity were accompanied by amino acid substitutions in viral hemagglutinin (HA) and PB2. In addition, the adapted viruses exhibited a reduced ability to react with ferret antisera against A/N. In conclusion, prolonged passaging allowed influenza A/N to adapt to different hosts, as indicated by a high increase in proliferative capacity that was accompanied by an antigenic alteration leading to amino acid substitutions. PMID:26079133

  13. Social class based on occupation is associated with hospitalization for A(H1N1)pdm09 infection. Comparison between hospitalized and ambulatory cases.

    PubMed

    Pujol, J; Godoy, P; Soldevila, N; Castilla, J; González-Candelas, F; Mayoral, J M; Astray, J; Garcia, S; Martin, V; Tamames, S; Delgado, M; Domínguez, A

    2016-03-01

    This study aimed to analyse the existence of an association between social class (categorized by type of occupation) and the occurrence of A(H1N1)pmd09 infection and hospitalization for two seasons (2009-2010 and 2010-2011). This multicentre study compared ambulatory A(H1N1)pmd09 confirmed cases with ambulatory controls to measure risk of infection, and with hospitalized A(H1N1)pmd09 confirmed cases to asses hospitalization risk. Study variables were: age, marital status, tobacco and alcohol use, pregnancy, chronic obstructive pulmonary disease, chronic respiratory failure, cardiovascular disease, diabetes, chronic liver disease, body mass index >40, systemic corticosteroid treatment and influenza vaccination status. Occupation was registered literally and coded into manual and non-manual worker occupational social class groups. A conditional logistic regression analysis was performed. There were 720 hospitalized cases, 996 ambulatory cases and 1062 ambulatory controls included in the study. No relationship between occupational social class and A(H1N1)pmd09 infection was found [adjusted odds ratio (aOR) 0·97, 95% confidence interval (CI) 0·74-1·27], but an association (aOR 1·53, 95% CI 1·01-2·31) between occupational class and hospitalization for A(H1N1)pmd09 was observed. Influenza vaccination was a protective factor for A(H1N1)pmd09 infection (aOR 0·41, 95% CI 0·23-0·73) but not for hospitalization. We conclude that manual workers have the highest risk of hospitalization when infected by influenza than other occupations but they do not have a different probability of being infected by influenza. PMID:26271901

  14. Safety of AS03-adjuvanted inactivated split virion A(H1N1)pdm09 and H5N1 influenza virus vaccines administered to adults: pooled analysis of 28 clinical trials.

    PubMed

    Vaughn, David W; Seifert, Harry; Hepburn, Anne; Dewe, Walthere; Li, Ping; Drame, Mamadou; Cohet, Catherine; Innis, Bruce L; Fries, Louis F

    2014-01-01

    Clinical trials have shown that AS03-adjuvanted H5N1 and A(H1N1)pdm09 vaccines are highly immunogenic, although with an increased reactogenicity profile relative to non-adjuvanted vaccines in terms of the incidence of common injection site and systemic adverse events (AEs). We evaluated pooled safety data from 22,521 adults who had received an AS03-adjuvanted H5N1 or A(H1N1)pdm09 influenza or control vaccine with the purpose to identify medically-attended AEs (MAEs), including subsets of serious AEs (SAEs), potentially immune-mediated diseases (pIMDs), and AEs of special interest (AESI), and to explore a potential association of these AEs with the administration of an AS03-adjuvanted influenza vaccine. For participants who had received an AS03-adjuvanted vaccine, the relative risks (RRs) for experiencing a MAE or a SAE compared to control group (participants who had received a non-adjuvanted vaccine or saline placebo) were 1.0 (95% confidence interval [CI]: 0.9; 1.1) and 1.1 (95% CI: 0.9; 1.4), respectively. The overall RRs for experiencing an AESI or a pIMD (AS03-adjuvanted vaccine/control) were 1.2 (95% CI: 0.9; 1.6) and 1.7 (95% CI: 0.8; 3.8), respectively. Thirty-8 participants in the AS03-adjuvanted vaccine group had a pIMD reported after vaccine administration, yielding an incidence rate (IR) of 351.9 (95% CI: 249.1; 483.1) per 100,000 person-years. The estimated IRs in the AS03-adjuvanted vaccine group were greater than the literature reported rates for: facial paresis/VIIth nerve paralysis, celiac disease, thrombocytopenia and ulcerative colitis. These results do not support an association between AS03-adjuvanted H5N1 and A(H1N1)pdm09 vaccines and the AEs collected in the trials included in the analysis. PMID:25483467

  15. Influenza A(H1N1)pdm09 during air travel

    PubMed Central

    Neatherlin, John; Cramer, Elaine H.; Dubray, Christine; Marienau, Karen J.; Russell, Michelle; Sun, Hong; Whaley, Melissa; Hancock, Kathy; Duong, Krista K.; Kirking, Hannah L.; Schembri, Christopher; Katz, Jacqueline M.; Cohen, Nicole J.; Fishbein, Daniel B.

    2015-01-01

    Summary The global spread of the influenza A(H1N1)pdm09 virus (pH1N1) associated with travelers from North America during the onset of the 2009 pandemic demonstrates the central role of international air travel in virus migration. To characterize risk factors for pH1N1 transmission during air travel, we investigated travelers and airline employees from four North American flights carrying ill travelers with confirmed pH1N1 infection. Of 392 passengers and crew identified, information was available for 290 (74%) passengers were interviewed. Overall attack rates for acute respiratory infection and influenza-like illness 1–7 days after travel were 5.2% and 2.4% respectively. Of 43 individuals that provided sera, 4 (9.3%) tested positive for pH1N1 antibodies, including 3 with serologic evidence of asymptomatic infection. Investigation of novel influenza aboard aircraft may be instructive. However, beyond the initial outbreak phase, it may compete with community-based mitigation activities, and interpretation of findings will be difficult in the context of established community transmission. PMID:23523241

  16. Influenza A(H1N1)pdm09 during air travel.

    PubMed

    Neatherlin, John; Cramer, Elaine H; Dubray, Christine; Marienau, Karen J; Russell, Michelle; Sun, Hong; Whaley, Melissa; Hancock, Kathy; Duong, Krista K; Kirking, Hannah L; Schembri, Christopher; Katz, Jacqueline M; Cohen, Nicole J; Fishbein, Daniel B

    2013-01-01

    The global spread of the influenza A(H1N1)pdm09 virus (pH1N1) associated with travelers from North America during the onset of the 2009 pandemic demonstrates the central role of international air travel in virus migration. To characterize risk factors for pH1N1 transmission during air travel, we investigated travelers and airline employees from four North American flights carrying ill travelers with confirmed pH1N1 infection. Of 392 passengers and crew identified, information was available for 290 (74%) passengers were interviewed. Overall attack rates for acute respiratory infection and influenza-like illness 1-7 days after travel were 5.2% and 2.4% respectively. Of 43 individuals that provided sera, 4 (9.3%) tested positive for pH1N1 antibodies, including 3 with serologic evidence of asymptomatic infection. Investigation of novel influenza aboard aircraft may be instructive. However, beyond the initial outbreak phase, it may compete with community-based mitigation activities, and interpretation of findings will be difficult in the context of established community transmission. PMID:23523241

  17. Socioeconomic Factors Influencing Hospitalized Patients with Pneumonia Due to Influenza A(H1N1)pdm09 in Mexico

    PubMed Central

    Manabe, Toshie; Higuera Iglesias, Anjarath Lorena; Vazquez Manriquez, Maria Eugenia; Martinez Valadez, Eduarda Leticia; Ramos, Leticia Alfaro; Izumi, Shinyu; Takasaki, Jin; Kudo, Koichiro

    2012-01-01

    Background In addition to clinical aspects and pathogen characteristics, people's health-related behavior and socioeconomic conditions can affect the occurrence and severity of diseases including influenza A(H1N1)pdm09. Methodology and Principal Findings A face-to-face interview survey was conducted in a hospital in Mexico City at the time of follow-up consultation for hospitalized patients with pneumonia due to influenza virus infection. In all, 302 subjects were enrolled and divided into two groups based on the period of hospitalization. Among them, 211 tested positive for influenza A(H1N1)pdm09 virus by real-time reverse-transcriptase-polymerase-chain-reaction during the pandemic period (Group-pdm) and 91 tested positive for influenza A virus in the post-pandemic period (Group-post). All subjects were treated with oseltamivir. Data on the demographic characteristics, socioeconomic status, living environment, and information relating to A(H1N1)pdm09, and related clinical data were compared between subjects in Group-pdm and those in Group-post. The ability of household income to pay for utilities, food, and health care services as well as housing quality in terms of construction materials and number of rooms revealed a significant difference: Group-post had lower socioeconomic status than Group-pdm. Group-post had lower availability of information regarding H1N1 influenza than Group-pdm. These results indicate that subjects in Group-post had difficulty receiving necessary information relating to influenza and were more likely to be impoverished than those in Group-pdm. Possible factors influencing time to seeking health care were number of household rooms, having received information on the necessity of quick access to health care, and house construction materials. Conclusions Health-care-seeking behavior, poverty level, and the distribution of information affect the occurrence and severity of pneumonia due to H1N1 virus from a socioeconomic point of view. These

  18. Household Transmission of Influenza A(H1N1)pdm09 in the Pandemic and Post-Pandemic Seasons

    PubMed Central

    Casado, Itziar; Martínez-Baz, Iván; Burgui, Rosana; Irisarri, Fátima; Arriazu, Maite; Elía, Fernando; Navascués, Ana; Ezpeleta, Carmen; Aldaz, Pablo; Castilla, Jesús

    2014-01-01

    Background The transmission of influenza viruses occurs person to person and is facilitated by contacts within enclosed environments such as households. The aim of this study was to evaluate secondary attack rates and factors associated with household transmission of laboratory-confirmed influenza A(H1N1)pdm09 in the pandemic and post-pandemic seasons. Methods During the 2009–2010 and 2010–2011 influenza seasons, 76 sentinel physicians in Navarra, Spain, took nasopharyngeal and pharyngeal swabs from patients diagnosed with influenza-like illness. A trained nurse telephoned households of those patients who were laboratory-confirmed for influenza A(H1N1)pdm09 to ask about the symptoms, risk factors and vaccination status of each household member. Results In the 405 households with a patient laboratory-confirmed for influenza A(H1N1)pdm09, 977 susceptible contacts were identified; 16% of them (95% CI 14–19%) presented influenza-like illness and were considered as secondary cases. The secondary attack rate was 14% in 2009–2010 and 19% in the 2010–2011 season (p = 0.049), an increase that mainly affected persons with major chronic conditions. In the multivariate logistic regression analysis, the risk of being a secondary case was higher in the 2010–2011 season than in the 2009–2010 season (adjusted odds ratio: 1.72; 95% CI 1.17–2.54), and in children under 5 years, with a decreasing risk in older contacts. Influenza vaccination was associated with lesser incidence of influenza-like illness near to statistical significance (adjusted odds ratio: 0.29; 95% CI 0.08–1.03). Conclusion The secondary attack rate in households was higher in the second season than in the first pandemic season. Children had a greater risk of infection. Preventive measures should be maintained in the second pandemic season, especially in high-risk persons. PMID:25254376

  19. HIV-1 and Its gp120 Inhibits the Influenza A(H1N1)pdm09 Life Cycle in an IFITM3-Dependent Fashion

    PubMed Central

    Mesquita, Milene; Fintelman-Rodrigues, Natalia; Sacramento, Carolina Q.; Abrantes, Juliana L.; Costa, Eduardo; Temerozo, Jairo R.; Siqueira, Marilda M.; Bou-Habib, Dumith Chequer; Souza, Thiago Moreno L.

    2014-01-01

    HIV-1-infected patients co-infected with A(H1N1)pdm09 surprisingly presented benign clinical outcome. The knowledge that HIV-1 changes the host homeostatic equilibrium, which may favor the patient resistance to some co-pathogens, prompted us to investigate whether HIV-1 infection could influence A(H1N1)pdm09 life cycle in vitro. We show here that exposure of A(H1N1)pdm09-infected epithelial cells to HIV-1 viral particles or its gp120 enhanced by 25% the IFITM3 content, resulting in a decrease in influenza replication. This event was dependent on toll-like receptor 2 and 4. Moreover, knockdown of IFITM3 prevented HIV-1 ability to inhibit A(H1N1)pdm09 replication. HIV-1 infection also increased IFITM3 levels in human primary macrophages by almost 100%. Consequently, the arrival of influenza ribonucleoproteins (RNPs) to nucleus of macrophages was inhibited, as evaluated by different approaches. Reduction of influenza RNPs entry into the nucleus tolled A(H1N1)pdm09 life cycle in macrophages earlier than usual, limiting influenza's ability to induce TNF-α. As judged by analysis of the influenza hemagglutin (HA) gene from in vitro experiments and from samples of HIV-1/A(H1N1)pdm09 co-infected individuals, the HIV-1-induced reduction of influenza replication resulted in delayed viral evolution. Our results may provide insights on the mechanisms that may have attenuated the clinical course of Influenza in HIV-1/A(H1N1)pdm09 co-infected patients during the recent influenza form 2009/2010. PMID:24978204

  20. Siaα2-3Galβ1- Receptor Genetic Variants Are Associated with Influenza A(H1N1)pdm09 Severity

    PubMed Central

    Tovo-Rodrigues, Luciana; Santos, Mirleide Cordeiro; Barbagelata, Luana; Moraes, Milene Raiol; Alencar de Mello, Wyller; Gusmão, Leonor; Sousa, Rita Catarina Medeiros; Emanuel Batista dos Santos, Sidney

    2015-01-01

    Different host genetic variants may be related to the virulence and transmissibility of pandemic Influenza A(H1N1)pdm09, influencing events such as binding of the virus to the entry receptor on the cell of infected individuals and the host immune response. In the present study, two genetic variants of the ST3GAL1 gene, which encodes the Siaα2-3Galβ1- receptor to which influenza A(H1N1)pdm09 virus binds for entry into the host cell, were investigated in an admixed Brazilian population. First, the six exons encoding the ST3GAL1 gene were sequenced in 68 patients infected with strain A(H1N1)pdm09. In a second phase of the study, the rs113350588 and rs1048479 polymorphisms identified in this sample were genotyped in a sample of 356 subjects from the northern and northeastern regions of Brazil with a diagnosis of pandemic influenza. Functional analysis of the polymorphisms was performed in silico and the influence of these variants on the severity of infection was evaluated. The results suggest that rs113350588 and rs1048479 may alter the function of ST3GAL1 either directly through splicing regulation alteration and/or indirectly through LD with SNP with regulatory function. In the study the rs113350588 and rs1048479 polymorphisms were in linkage disequilibrium in the population studied (D’ = 0.65). The GC haplotype was associated with an increased risk of death in subjects with influenza (OR = 4.632, 95% CI = 2.10;1.21). The AT haplotype was associated with an increased risk of severe disease and death (OR = 1.993, 95% CI = 1.09;3.61 and OR 4.476, 95% CI = 2.37;8.44, respectively). This study demonstrated for the first time the association of ST3GAL1 gene haplotypes on the risk of more severe disease and death in patients infected with Influenza A(H1N1)pdm09 virus. PMID:26436774

  1. Siaα2-3Galβ1- Receptor Genetic Variants Are Associated with Influenza A(H1N1)pdm09 Severity.

    PubMed

    Maestri, Alvino; Sortica, Vinicius Albuquerque; Tovo-Rodrigues, Luciana; Santos, Mirleide Cordeiro; Barbagelata, Luana; Moraes, Milene Raiol; Alencar de Mello, Wyller; Gusmão, Leonor; Sousa, Rita Catarina Medeiros; Emanuel Batista Dos Santos, Sidney

    2015-01-01

    Different host genetic variants may be related to the virulence and transmissibility of pandemic Influenza A(H1N1)pdm09, influencing events such as binding of the virus to the entry receptor on the cell of infected individuals and the host immune response. In the present study, two genetic variants of the ST3GAL1 gene, which encodes the Siaα2-3Galβ1- receptor to which influenza A(H1N1)pdm09 virus binds for entry into the host cell, were investigated in an admixed Brazilian population. First, the six exons encoding the ST3GAL1 gene were sequenced in 68 patients infected with strain A(H1N1)pdm09. In a second phase of the study, the rs113350588 and rs1048479 polymorphisms identified in this sample were genotyped in a sample of 356 subjects from the northern and northeastern regions of Brazil with a diagnosis of pandemic influenza. Functional analysis of the polymorphisms was performed in silico and the influence of these variants on the severity of infection was evaluated. The results suggest that rs113350588 and rs1048479 may alter the function of ST3GAL1 either directly through splicing regulation alteration and/or indirectly through LD with SNP with regulatory function. In the study the rs113350588 and rs1048479 polymorphisms were in linkage disequilibrium in the population studied (D' = 0.65). The GC haplotype was associated with an increased risk of death in subjects with influenza (OR = 4.632, 95% CI = 2.10;1.21). The AT haplotype was associated with an increased risk of severe disease and death (OR = 1.993, 95% CI = 1.09;3.61 and OR 4.476, 95% CI = 2.37;8.44, respectively). This study demonstrated for the first time the association of ST3GAL1 gene haplotypes on the risk of more severe disease and death in patients infected with Influenza A(H1N1)pdm09 virus. PMID:26436774

  2. Hospitalization Fatality Risk of Influenza A(H1N1)pdm09: A Systematic Review and Meta-Analysis

    PubMed Central

    Wong, Jessica Y.; Kelly, Heath; Cheung, Chung-Mei M.; Shiu, Eunice Y.; Wu, Peng; Ni, Michael Y.; Ip, Dennis K. M.; Cowling, Benjamin J.

    2015-01-01

    During the 2009 influenza pandemic, uncertainty surrounding the severity of human infections with the influenza A(H1N1)pdm09 virus hindered the calibration of the early public health response. The case fatality risk was widely used to assess severity, but another underexplored and potentially more immediate measure is the hospitalization fatality risk (HFR), defined as the probability of death among H1N1pdm09 cases who required hospitalization for medical reasons. In this review, we searched for relevant studies published in MEDLINE (PubMed) and EMBASE between April 1, 2009, and January 9, 2014. Crude estimates of the HFR ranged from 0% to 52%, with higher estimates from tertiary-care referral hospitals in countries with a lower gross domestic product, but in wealthy countries the estimate was 1%–3% in all settings. Point estimates increased substantially with age and with lower gross domestic product. Early in the next pandemic, estimation of a standardized HFR may provide a picture of the severity of infection, particularly if it is presented in comparison with a similarly standardized HFR for seasonal influenza in the same setting. PMID:26188191

  3. Risk of Guillain-Barré syndrome after exposure to pandemic influenza A(H1N1)pdm09 vaccination or infection: a Norwegian population-based cohort study.

    PubMed

    Ghaderi, Sara; Gunnes, Nina; Bakken, Inger Johanne; Magnus, Per; Trogstad, Lill; Håberg, Siri Eldevik

    2016-01-01

    Vaccinations and infections are possible triggers of Guillain-Barré syndrome (GBS). However, studies on GBS after vaccinations during the influenza A(H1N1)pmd09 pandemic in 2009, show inconsistent results. Only few studies have addressed the role of influenza infection. We used information from national health data-bases with information on the total Norwegian population (N = 4,832,211). Cox regression analyses with time-varying covariates and self-controlled case series was applied. The risk of being hospitalized with GBS during the pandemic period, within 42 days after an influenza diagnosis or pandemic vaccination was estimated. There were 490 GBS cases during 2009-2012 of which 410 cases occurred after October 1, 2009 of which 46 new cases occurred during the peak period of the influenza pandemic. An influenza diagnosis was registered for 2.47% of the population and the vaccination coverage was 39.25%. The incidence rate ratio of GBS during the pandemic peak relative to other periods was 1.46 [95% confidence interval (CI) 1.08-1.98]. The adjusted hazard ratio (HR) of GBS within 42 days after a diagnosis of pandemic influenza was 4.89 (95% CI 1.17-20.36). After pandemic vaccination the adjusted HR was 1.11 (95% CI 0.51-2.43). Our results indicated that there was a significantly increased risk of GBS during the pandemic season and after pandemic influenza infection. However, vaccination did not increase the risk of GBS. The small number of GBS cases in this study warrants caution in the interpretation of the findings. PMID:26008750

  4. Immunogenicity of influenza A(H1N1)pdm09 vaccine in patients with diabetes mellitus

    PubMed Central

    Egawa, Yumi; Ohfuji, Satoko; Fukushima, Wakaba; Yamazaki, Yuko; Morioka, Tomoaki; Emoto, Masanori; Maeda, Kazuhiro; Inaba, Masaaki; Hirota, Yoshio

    2014-01-01

    Subjects with diabetes mellitus are considered to be at high risk of influenza infection and influenza-associated complications. To evaluate the immunogenicity of the influenza A(H1N1)pdm09 vaccine among these subjects, we performed a prospective cohort study and measured hemagglutination inhibition antibody titers at baseline and 3 weeks after vaccination in 49 patients. No serious adverse events were reported. We were able to perform analyses for 48 patients, after excluding one patient with suspected infection. The vaccine induced a rise of about 9-fold in the mean antibody level. The sero-response proportion was 79%, and the sero-protection proportion was 73%. Patients with older age and lower body mass index tended to show lower immune response. Multivariate analysis indicated an independent negative effect of hemoglobin A1c level on the sero-protection proportion. A single A(H1N1)pdm09 vaccination achieved a sufficient level of immunity among diabetic patients, but both clinicians and patients should be aware of the potential for reductions in immune response. PMID:24717236

  5. Clinical epidemiology and predictors of outcome in children hospitalised with influenza A(H1N1)pdm09 in 2009: a prospective national study

    PubMed Central

    Khandaker, Gulam; Zurynski, Yvonne; Ridley, Greta; Buttery, Jim; Marshall, Helen; Richmond, Peter C; Royle, Jenny; Gold, Michael; Walls, Tony; Whitehead, Bruce; McIntyre, Peter; Wood, Nicholas; Booy, Robert; Elliott, Elizabeth J

    2014-01-01

    Background There are few large-scale, prospective studies of influenza A(H1N1)pdm09 in children that identify predictors of adverse outcomes. Objectives We aimed to examine clinical epidemiology and predictors for adverse outcomes in children hospitalised with influenza A(H1N1)pdm09 in Australia. Methods Active hospital surveillance in six tertiary paediatric referral centres (June–September, 2009). All children aged <15 years admitted with laboratory-confirmed influenza A(H1N1)pdm09 were studied. Results Of 601 children admitted with laboratory-confirmed influenza, 506 (84·2%) had influenza A(H1N1)pdm09. Half (51·0%) of children with influenza A(H1N1)pdm09 were previously healthy. Hospital stay was longer in children with pre-existing condition (mean 6·9 versus 4·9 days; P = 0·02) as was paediatric intensive care unit (PICU) stay (7·0 versus 2·3 days; P = 0·005). Rapid diagnosis decreased both antibiotic use and length of hospital and PICU stay. Fifty (9·9%) children were admitted to a PICU, 30 (5·9%) required mechanical ventilation and 5 (0·9%) died. Laboratory-proven bacterial co-infection and chronic lung disease were significant independent predictors of PICU admission (OR 6·89, 95% CI 3·15–15·06 and OR 3·58, 95% CI 1·41–9·07, respectively) and requirement for ventilation (OR 5·61, 95% CI 2·2–14·28 and OR 5·18, 95% CI 1·8–14·86, respectively). Chronic neurological disease was a predictor of admission to PICU (OR 2·30, 95% CI 1·14–4·61). Conclusions During the 2009 pandemic, influenza was a major cause of hospitalisation in tertiary paediatric hospitals. Co-infection and underlying chronic disease increased risk of PICU admission and/or ventilation. Half the children admitted were previously healthy, supporting a role for universal influenza vaccination in children. PMID:25263176

  6. Clinical aspects of influenza A(H1N1)pdm09 cases reported during the pandemic in Brazil, 2009-2010

    PubMed Central

    Rossetto, Érika Valeska; Luna, Expedito José de Albuquerque

    2015-01-01

    ABSTRACT Objective: To describe the clinical aspects of cases of influenza A(H1N1)pdm09 in Brazil. Methods: A descriptive study of cases reported in Sistema de Informação de Agravos de Notificação (SINAN), 2009-2010. Results: As the final classification, we obtained 53,797 (56.79%) reported cases confirmed as a new influenza virus subtype, and 40,926 (43.21%) cases discarded. Fever was the most common sign, recorded in 99.74% of the confirmed and 98.92% of the discarded cases. Among the confirmed cases, the presence of comorbidities was reported in 32.53%, and in 38.29% of the discarded cases. The case fatality rate was 4.04%; 3,267 pregnant women were confirmed positive for influenza A new viral subtype and 2,730 of them were cured. The case fatality rate of pregnant women was 6.88%. Conclusion: The findings suggested concern of the health system with pregnant women, and patients with comorbidities and quality of care may have favored a lower mortality. We recommend that, when caring for patients with severe respiratory symptoms, with comorbidities, or pregnant women, health professionals should consider the need for hospital care, as these factors make up a worse prognosis of infection by the pandemic influenza virus. PMID:26154537

  7. Pandemic vaccination strategies and influenza severe outcomes during the influenza A(H1N1)pdm09 pandemic and the post-pandemic influenza season: the Nordic experience.

    PubMed

    Cuesta, Julita Gil; Aavitsland, Preben; Englund, Hélène; Gudlaugsson, Ólafur; Hauge, Siri Helene; Lyytikäinen, Outi; Sigmundsdóttir, Guðrún; Tegnell, Anders; Virtanen, Mikko; Krause, Tyra Grove

    2016-04-21

    During the 2009/10 influenza A(H1N1)pdm09 pandemic, the five Nordic countries adopted different approaches to pandemic vaccination. We compared pandemic vaccination strategies and severe influenza outcomes, in seasons 2009/10 and 2010/11 in these countries with similar influenza surveillance systems. We calculated the cumulative pandemic vaccination coverage in 2009/10 and cumulative incidence rates of laboratory confirmed A(H1N1)pdm09 infections, intensive care unit (ICU) admissions and deaths in 2009/10 and 2010/11. We estimated incidence risk ratios (IRR) in a Poisson regression model to compare those indicators between Denmark and the other countries. The vaccination coverage was lower in Denmark (6.1%) compared with Finland (48.2%), Iceland (44.1%), Norway (41.3%) and Sweden (60.0%). In 2009/10 Denmark had a similar cumulative incidence of A(H1N1)pdm09 ICU admissions and deaths compared with the other countries. In 2010/11 Denmark had a significantly higher cumulative incidence of A(H1N1)pdm09 ICU admissions (IRR: 2.4; 95% confidence interval (CI): 1.9-3.0) and deaths (IRR: 8.3; 95% CI: 5.1-13.5). Compared with Denmark, the other countries had higher pandemic vaccination coverage and experienced less A(H1N1)pdm09-related severe outcomes in 2010/11. Pandemic vaccination may have had an impact on severe influenza outcomes in the post-pandemic season. Surveillance of severe outcomes may be used to compare the impact of influenza between seasons and support different vaccination strategies. PMID:27123691

  8. SPATIOTEMPORAL TRENDS OF CASES OF PANDEMIC INFLUENZA A(H1N1)PDM09 IN ARGENTINA, 2009-2012

    PubMed Central

    LEVEAU, Carlos M.; UEZ, Osvaldo; VACCHINO, Marta N.

    2015-01-01

    The aim of this paper was to analyze the spatiotemporal variations of cases of influenza A(H1N1)pdm09 in Argentina. A space-time permutation scan statistic was performed to test the non-randomness in the interaction between space and time in reported influenza A(H1N1)pdm09 cases. In 2009, two clusters were recorded in the east of Buenos Aires Province (May and June) and in the central and northern part of Argentina (July and August). Between 2011 and 2012, clusters near areas bordering other countries were registered. Within the clusters, in 2009, the high notification rates were first observed in the school-age population and then extended to the older population (15-59 years). From 2011 onwards, higher rates of reported cases of influenza A(H1N1)pdm09 occurred in children under five years in center of the country. Two stages of transmission of influenza A(H1N1)pdm09 can be characterized. The first stage had high rates of notification and a possible interaction with individuals from other countries in the major cities of Argentina (pattern of hierarchy), and the second stage had an increased interaction in some border areas without a clear pattern of hierarchy. These results suggest the need for greater coordination in the Southern Cone countries, in order to implement joint prevention and vaccination policies. PMID:25923892

  9. Spatiotemporal trends of cases of pandemic influenza A(H1N1)pdm09 in Argentina, 2009-2012.

    PubMed

    Leveau, Carlos M; Uez, Osvaldo; Vacchino, Marta N

    2015-01-01

    The aim of this paper was to analyze the spatiotemporal variations of cases of influenza A(H1N1)pdm09 in Argentina. A space-time permutation scan statistic was performed to test the non-randomness in the interaction between space and time in reported influenza A(H1N1)pdm09 cases. In 2009, two clusters were recorded in the east of Buenos Aires Province (May and June) and in the central and northern part of Argentina (July and August). Between 2011 and 2012, clusters near areas bordering other countries were registered. Within the clusters, in 2009, the high notification rates were first observed in the school-age population and then extended to the older population (15-59 years). From 2011 onwards, higher rates of reported cases of influenza A(H1N1)pdm09 occurred in children under five years in center of the country. Two stages of transmission of influenza A(H1N1)pdm09 can be characterized. The first stage had high rates of notification and a possible interaction with individuals from other countries in the major cities of Argentina (pattern of hierarchy), and the second stage had an increased interaction in some border areas without a clear pattern of hierarchy. These results suggest the need for greater coordination in the Southern Cone countries, in order to implement joint prevention and vaccination policies. PMID:25923892

  10. Molecular findings from influenza A(H1N1)pdm09 detected in patients from a Brazilian equatorial region during the pandemic period

    PubMed Central

    Oliveira, Maria José Couto; Motta, Fernando do Couto; Siqueira, Marilda M; Resende, Paola Cristina; Born, Priscilla da Silva; Souza, Thiago Moreno L; Mesquita, Milene; Oliveira, Maria de Lourdes Aguiar; Carney, Sharon; de Mello, Wyller Alencar; Magalhães, Vera

    2014-01-01

    After the World Health Organization officially declared the end of the first pandemic of the XXI century in August 2010, the influenza A(H1N1)pdm09 virus has been disseminated in the human population. In spite of its sustained circulation, very little on phylogenetic data or oseltamivir (OST) resistance is available for the virus in equatorial regions of South America. In order to shed more light on this topic, we analysed the haemagglutinin (HA) and neuraminidase (NA) genes of influenza A(H1N1)pdm09 positive samples collected during the pandemic period in the Pernambuco (PE), a northeastern Brazilian state. Complete HA sequences were compared and amino acid changes were related to clinical outcome. In addition, the H275Y substitution in NA, associated with OST resistance, was investigated by pyrosequencing. Samples from PE were grouped in phylogenetic clades 6 and 7, being clustered together with sequences from South and Southeast Brazil. The D222N/G HA gene mutation, associated with severity, was found in one deceased patient that was pregnant. Additionally, the HA mutation K308E, which appeared in Brazil in 2010 and was only detected worldwide the following year, was identified in samples from hospitalised cases. The resistance marker H275Y was not identified in samples tested. However, broader studies are needed to establish the real frequency of resistance in this Brazilian region. PMID:25410995

  11. Measuring the effect of influenza A(H1N1)pdm09: the epidemiological experience in the West Midlands, England during the 'containment' phase.

    PubMed

    Inglis, N J; Bagnall, H; Janmohamed, K; Suleman, S; Awofisayo, A; De Souza, V; Smit, E; Pebody, R; Mohamed, H; Ibbotson, S; Smith, G E; House, T; Olowokure, B

    2014-02-01

    The West Midlands was the first English region to report sustained community transmission during the 'containment' phase of the influenza A(H1N1)pdm09 pandemic in England. To describe the epidemiological experience in the region, West Midlands and national datasets containing laboratory-confirmed A(H1N1)pdm09 virus cases in the region during the 'containment' phase were analysed. The region accounts for about 10·5% of England's population, but reported about 42% of all laboratory-confirmed cases. Altogether 3063 cases were reported, with an incidence rate of 56/100 000 population. School-associated cases accounted for 25% of cases. Those aged <20 years, South Asian ethnic groups, and residents of urban and socioeconomically deprived areas were disproportionately affected. Imported cases accounted for 1% of known exposures. Regional R 0 central estimates between 1·41 and 1·43 were obtained. The West Midlands experience suggests that interpretation of transmission rates may be affected by complex interactions within and between sub-populations in the region. PMID:23731730

  12. Revealing the True Incidence of Pandemic A(H1N1)pdm09 Influenza in Finland during the First Two Seasons - An Analysis Based on a Dynamic Transmission Model.

    PubMed

    Shubin, Mikhail; Lebedev, Artem; Lyytikäinen, Outi; Auranen, Kari

    2016-03-01

    The threat of the new pandemic influenza A(H1N1)pdm09 imposed a heavy burden on the public health system in Finland in 2009-2010. An extensive vaccination campaign was set up in the middle of the first pandemic season. However, the true number of infected individuals remains uncertain as the surveillance missed a large portion of mild infections. We constructed a transmission model to simulate the spread of influenza in the Finnish population. We used the model to analyse the two first years (2009-2011) of A(H1N1)pdm09 in Finland. Using data from the national surveillance of influenza and data on close person-to-person (social) contacts in the population, we estimated that 6% (90% credible interval 5.1 - 6.7%) of the population was infected with A(H1N1)pdm09 in the first pandemic season (2009/2010) and an additional 3% (2.5 - 3.5%) in the second season (2010/2011). Vaccination had a substantial impact in mitigating the second season. The dynamic approach allowed us to discover how the proportion of detected cases changed over the course of the epidemic. The role of time-varying reproduction number, capturing the effects of weather and changes in behaviour, was important in shaping the epidemic. PMID:27010206

  13. Revealing the True Incidence of Pandemic A(H1N1)pdm09 Influenza in Finland during the First Two Seasons — An Analysis Based on a Dynamic Transmission Model

    PubMed Central

    Shubin, Mikhail; Lebedev, Artem; Lyytikäinen, Outi; Auranen, Kari

    2016-01-01

    The threat of the new pandemic influenza A(H1N1)pdm09 imposed a heavy burden on the public health system in Finland in 2009-2010. An extensive vaccination campaign was set up in the middle of the first pandemic season. However, the true number of infected individuals remains uncertain as the surveillance missed a large portion of mild infections. We constructed a transmission model to simulate the spread of influenza in the Finnish population. We used the model to analyse the two first years (2009-2011) of A(H1N1)pdm09 in Finland. Using data from the national surveillance of influenza and data on close person-to-person (social) contacts in the population, we estimated that 6% (90% credible interval 5.1 – 6.7%) of the population was infected with A(H1N1)pdm09 in the first pandemic season (2009/2010) and an additional 3% (2.5 – 3.5%) in the second season (2010/2011). Vaccination had a substantial impact in mitigating the second season. The dynamic approach allowed us to discover how the proportion of detected cases changed over the course of the epidemic. The role of time-varying reproduction number, capturing the effects of weather and changes in behaviour, was important in shaping the epidemic. PMID:27010206

  14. 2012/13 influenza vaccine effectiveness against hospitalised influenza A(H1N1)pdm09, A(H3N2) and B: estimates from a European network of hospitals.

    PubMed

    Rondy, M; Launay, O; Puig-Barberà, J; Gefenaite, G; Castilla, J; de Gaetano Donati, K; Galtier, F; Hak, E; Guevara, M; Costanzo, S; Moren, A

    2015-01-01

    While influenza vaccines aim to decrease the incidence of severe influenza among high-risk groups, evidence of influenza vaccine effectiveness (IVE) among the influenza vaccine target population is sparse. We conducted a multicentre test-negative case-control study to estimate IVE against hospitalised laboratory-confirmed influenza in the target population in 18 hospitals in France, Italy, Lithuania and the Navarre and Valencia regions in Spain. All hospitalised patients aged ≥18 years, belonging to the target population presenting with influenza-like illness symptom onset within seven days were swabbed. Patients positive by reverse transcription polymerase chain reaction for influenza virus were cases and those negative were controls. Using logistic regression, we calculated IVE for each influenza virus subtype and adjusted it for month of symptom onset, study site, age and chronic conditions. Of the 1,972 patients included, 116 were positive for influenza A(H1N1)pdm09, 58 for A(H3N2) and 232 for influenza B. Adjusted IVE was 21.3% (95% confidence interval (CI): -25.2 to 50.6; n=1,628), 61.8% (95% CI: 26.8 to 80.0; n=557) and 43.1% (95% CI: 21.2 to 58.9; n=1,526) against influenza A(H1N1) pdm09, A(H3N2) and B respectively. Our results suggest that the 2012/13 IVE was moderate against influenza A(H3N2) and B and low against influenza A(H1N1) pdm09. PMID:25613779

  15. Case fatality risk of influenza A(H1N1pdm09): a systematic review

    PubMed Central

    Wong, Jessica Y.; Kelly, Heath; Ip, Dennis K. M.; Wu, Joseph T.; Leung, Gabriel M.; Cowling, Benjamin J.

    2013-01-01

    Background During the 2009 influenza pandemic, uncertainty surrounding the seriousness of human infections with the H1N1pdm09 virus hindered appropriate public health response. One measure of seriousness is the case fatality risk, defined as the probability of mortality among people classified as cases. Methods We conducted a systematic review to summarize published estimates of the case fatality risk of the pandemic influenza H1N1pdm09 virus. Only studies that reported population-based estimates were included. Results We included 77 estimates of the case fatality risk from 50 published studies, about one-third of which were published within the first 9 months of the pandemic. We identified very substantial heterogeneity in published estimates, ranging from less than 1 to more than 10,000 deaths per 100,000 cases or infections. The choice of case definition in the denominator accounted for substantial heterogeneity, with the higher estimates based on laboratory-confirmed cases (point estimates= 0–13,500 per 100,000 cases) compared with symptomatic cases (point estimates= 0–1,200 per 100,000 cases) or infections (point estimates=1–10 per 100,000 infections). Risk based on symptomatic cases increased substantially with age. Conclusions Our review highlights the difficulty in estimating the seriousness of infection with a novel influenza virus using the case fatality risk. In addition, substantial variability in age-specific estimates complicates the interpretation of the overall case fatality risk and comparisons among populations. A consensus is needed on how to define and measure the seriousness of infection before the next pandemic. PMID:24045719

  16. Immunogenicity of a monovalent influenza A(H1N1)pdm09 vaccine in patients with hematological malignancies

    PubMed Central

    Ide, Yuichiro; Imamura, Yutaka; Ohfuji, Satoko; Fukushima, Wakaba; Ide, Saburo; Tsutsumi, Chiyo; Koga, Masahisa; Maeda, Kazuhiro; Hirota, Yoshio

    2014-01-01

    Patients with hematological malignancies have high risk for morbidity and mortality from influenza. This study was conducted to evaluate the immunogenicity and reactogenicity of an influenza A(H1N1)pdm09 vaccine among such subjects. Fifty subjects were vaccinated twice during the 2009–2010 season. The antibody response was expressed in terms of mean fold rise (MFR) of geometric mean titer, seroresponse proportion (sR), and seroprotection proportion (sP). The first vaccination induced only a small response, and additional antibody was acquired after the second dose (MFR 2.3 and 3.9, sR 32% and 54%, and sP 30% and 48% after the first and the second vaccination, respectively). Rituximab treatment showed an especially inhibitory effect (MFR 1.3, sR 9% and sP 0%). When analyzed using logistic regression models, only rituximab was found to have an independent effect; the adjusted odds ratio for sR was 0.09 (P = 0.05). Influenza vaccination of patients with hematological malignancies resulted in adepuate response, and the second vaccination induced additional antibody. It is therefore recommended to vaccinate this group twice. PMID:25424946

  17. An Evaluation of Community Assessment Tools (CATs) in Predicting Use of Clinical Interventions and Severe Outcomes during the A(H1N1)pdm09 Pandemic

    PubMed Central

    Nicholson, Karl G.; Lim, Wei Shen; Read, Robert C.; Taylor, Bruce L.; Brett, Stephen J.; Openshaw, Peter J. M.; Enstone, Joanne E.; McMenamin, James; Bannister, Barbara; Nguyen-Van-Tam, Jonathan S.

    2013-01-01

    During severe influenza pandemics healthcare demand can exceed clinical capacity to provide normal standards of care. Community Assessment Tools (CATs) could provide a framework for triage decisions for hospital referral and admission. CATs have been developed based on evidence that supports the recognition of severe influenza and pneumonia in the community (including resource limited settings) for adults, children and infants, and serious feverish illness in children. CATs use six objective criteria and one subjective criterion, any one or more of which should prompt urgent referral and admission to hospital. A retrospective evaluation of the ability of CATs to predict use of hospital-based interventions and patient outcomes in a pandemic was made using the first recorded routine clinical assessment on or shortly after admission from 1520 unselected patients (800 female, 480 children <16 years) admitted with PCR confirmed A(H1N1)pdm09 infection (the FLU-CIN cohort). Outcome measures included: any use of supplemental oxygen; mechanical ventilation; intravenous antibiotics; length of stay; intensive or high dependency care; death; and “severe outcome” (combined: use of intensive or high dependency care or death during admission). Unadjusted and multivariable analyses were conducted for children (age <16 years) and adults. Each CATs criterion independently identified both use of clinical interventions that would in normal circumstances only be provided in hospital and patient outcome measures. “Peripheral oxygen saturation ≤92% breathing air, or being on oxygen” performed well in predicting use of resources and outcomes for both adults and children; supporting routine measurement of peripheral oxygen saturation when assessing severity of disease. In multivariable analyses the single subjective criterion in CATs “other cause for clinical concern” independently predicted death in children and in adults predicted length of stay, mechanical ventilation and

  18. International flight-related transmission of pandemic influenza A(H1N1)pdm09: an historical cohort study of the first identified cases in the United Kingdom

    PubMed Central

    Young, Nicholas; Pebody, Richard; Smith, Gillian; Olowokure, Babatunde; Shankar, Giri; Hoschler, Katja; Galiano, Monica; Green, Helen; Wallensten, Anders; Hogan, Angela; Oliver, Isabel

    2014-01-01

    Background Transporting over two billion passengers per year, global airline travel has the potential to spread emerging infectious diseases, both via transportation of infectious cases and through in-flight transmission. Current World Health Organization (WHO) guidance recommends contact tracing of passengers seated within two rows of a case of influenza during air travel. Objectives The objectives of this study were to describe flight-related transmission of influenza A(H1N1)pdm09 during a commercial flight carrying the first cases reported in the United Kingdom and to test the specific hypothesis that passengers seated within two rows of an infectious case are at greater risk of infection. Methods An historical cohort study, supplemented by contact tracing, enhanced surveillance data and laboratory testing, was used to establish a case status for passengers on board the flight. Results Data were available for 239 of 278 (86·0%) of passengers on the flight, of whom six were considered infectious in-flight and one immune. The attack rate (AR) was 10 of 232 (4·3%; 95% CI 1·7–6·9%). There was no evidence that the AR for those seated within two rows of an infectious case was different from those who were not (relative risk 0·9; 95% CI 0·2–3·1; P = 1·00). Laboratory testing using PCR and/or serology, available for 118 of 239 (49·4%) of the passengers, was largely consistent with clinically defined case status. Conclusions This study of A(H1N1)pdm09 does not support current WHO guidance regarding the contact tracing of passengers seated within two rows of an infectious case of influenza during air travel. PMID:24373291

  19. Pathogenicity and Transmissibility of Novel Reassortant H3N2 Influenza Viruses with 2009 Pandemic H1N1 Genes in Pigs

    PubMed Central

    Ma, Jingjiao; Shen, Huigang; Liu, Qinfang; Bawa, Bhupinder; Qi, Wenbao; Duff, Michael; Lang, Yuekun; Lee, Jinhwa; Yu, Hai; Bai, Jianfa; Tong, Guangzhi; Hesse, Richard A.; Richt, Jürgen A.

    2014-01-01

    ABSTRACT At least 10 different genotypes of novel reassortant H3N2 influenza viruses with 2009 pandemic H1N1 [A(H1N1)pdm09] gene(s) have been identified in U.S. pigs, including the H3N2 variant with a single A(H1N1)pdm09 M gene, which has infected more than 300 people. To date, only three genotypes of these viruses have been evaluated in animal models, and the pathogenicity and transmissibility of the other seven genotype viruses remain unknown. Here, we show that three H3N2 reassortant viruses that contain 3 (NP, M, and NS) or 5 (PA, PB2, NP, M, and NS) genes from A(H1N1)pdm09 were pathogenic in pigs, similar to the endemic H3N2 swine virus. However, the reassortant H3N2 virus with 3 A(H1N1)pdm09 genes and a recent human influenza virus N2 gene was transmitted most efficiently among pigs, whereas the reassortant H3N2 virus with 5 A(H1N1)pdm09 genes was transmitted less efficiently than the endemic H3N2 virus. Interestingly, the polymerase complex of reassortant H3N2 virus with 5 A(H1N1)pdm09 genes showed significantly higher polymerase activity than those of endemic and reassortant H3N2 viruses with 3 A(H1N1)pdm09 genes. Further studies showed that an avian-like glycine at position 228 at the hemagglutinin (HA) receptor binding site is responsible for inefficient transmission of the reassortant H3N2 virus with 5 A(H1N1)pdm09 genes. Taken together, our results provide insights into the pathogenicity and transmissibility of novel reassortant H3N2 viruses in pigs and suggest that a mammalian-like serine at position 228 in the HA is critical for the transmissibility of these reassortant H3N2 viruses. IMPORTANCE Swine influenza is a highly contagious zoonotic disease that threatens animal and public health. Introduction of 2009 pandemic H1N1 virus [A(H1N1)pdm09] into swine herds has resulted in novel reassortant influenza viruses in swine, including H3N2 and H1N2 variants that have caused human infections in the United States. We showed that reassortant H3N2 influenza

  20. Molecular epidemiology and phylogenetic analysis of HA gene of influenza A(H1N1)pdm09 strain during 2010-2014 in Dalian, North China.

    PubMed

    Han, Yan; Sun, Nan; Lv, Qiu-Yue; Liu, Dan-Hong; Liu, Da-Peng

    2016-10-01

    The objective of the present study was to evaluate the epidemiology of influenza A(H1N1)pdm09 and its hemagglutinin (HA) molecular and phylogenetic analysis during 2010-2014 in Dalian, North China. A total of 3717 influenza-like illness (ILI) cases were tested by real-time PCR and 493 were found to be positive. Out of these 493 cases, 121 were subtype influenza A(H1N1)pdm09, of which 14 cases were reported in 2010-2011, 29 in 2012-2013, and 78 in 2013-2014. HA coding regions of 45 isolates were compared to that of the vaccine strain A/California/7/09(H1N1), and a number of variations were detected. P83S, S185T, S203T, R223Q, and I321V mutations were observed in all of the Dalian isolates. Furthermore, a high proportion >71 % of the strains possessed the variation D97N and K283E. Phylogenetic analysis confirmed the close match of the majority of circulating strains with the vaccine strains. However, it also reveals a trend of strains to accumulate amino acid variations and form new phylogenetic groups. PMID:27251702

  1. PD-L1 Expression Induced by the 2009 Pandemic Influenza A(H1N1) Virus Impairs the Human T Cell Response

    PubMed Central

    Arriaga-Pizano, Lourdes; Ferat-Osorio, Eduardo; Mora-Velandia, Luz María; Pastelin-Palacios, Rodolfo; Villasís-Keever, Miguel Ángel; Alpuche-Aranda, Celia; Sánchez-Torres, Luvia Enid; Isibasi, Armando; Bonifaz, Laura; López-Macías, Constantino

    2013-01-01

    PD-L1 expression plays a critical role in the impairment of T cell responses during chronic infections; however, the expression of PD-L1 on T cells during acute viral infections, particularly during the pandemic influenza virus (A(H1N1)pdm09), and its effects on the T cell response have not been widely explored. We found that A(H1N1)pdm09 virus induced PD-L1 expression on human dendritic cells (DCs) and T cells, as well as PD-1 expression on T cells. PD-L1 expression impaired the T cell response against A(H1N1)pdm09 by promoting CD8+ T cell death and reducing cytokine production. Furthermore, we found increased PD-L1 expression on DCs and T cells from influenza-infected patients from the first and second 2009 pandemic waves in Mexico City. PD-L1 expression on CD8+ T cells correlated inversely with T cell proportions in patients infected with A(H1N1)pdm09. Therefore, PD-L1 expression on DCs and T cells could be associated with an impaired T cell response during acute infection with A(H1N1)pdm09 virus. PMID:24187568

  2. Pandemic 2009 influenza A (H1N1) infection among 2009 Hajj Pilgrims from Southern Iran: a real‐time RT‐PCR‐based study

    PubMed Central

    Ziyaeyan, Mazyar; Alborzi, Abdolvahab; Jamalidoust, Marziyeh; Moeini, Mahsa; Pouladfar, Gholam R.; Pourabbas, Bahman; Namayandeh, Mandana; Moghadami, Mohsen; Bagheri‐Lankarani, Kamran; Mokhtari‐Azad, Talat

    2012-01-01

    Please cite this paper as: Ziyaeyan et al. (2012) Pandemic 2009 influenza A H1N1 infection among 2009 Hajj Pilgrims from Southern Iran: a real‐time RT‐PCR‐based study. Influenza and Other Respiratory Viruses 6(601), e80–e84. Background  Hajj is a mass gathering undertaken annually in Mecca, Saudi Arabia. The 2009 Hajj coincided with both the pandemic influenza A/H1N1 2009 (A(H1N1)pdm09) and seasonal types of influenza A viruses. The interaction between pandemic influenza and Hajj could cause both a high level of mortality among the pilgrims and the spread of infection in their respective countries upon their return home. Objective  The present study attempted to determine the point prevalence of A(H1N1)pdm09 among returning Iranian pilgrims, most of whom had been vaccinated for seasonal influenza but not A(H1N1)pdm09. Methods  Pharyngeal swabs were collected from 305 pilgrims arriving at the airport in Shiraz, Iran. RNA was extracted from the samples and A(H1N1)pdm09 and other seasonal influenza A viruses were detected using TaqMan real‐time PCR. For A(H1N1)pdm09‐positive samples, the sensitivity to oseltamivir was also evaluated. Results  Subjects included 132 (43·3%) men and 173 (56·7%) women, ranging in age from 24 to 65 years. The A(H1N1)pdm09 virus was detected in five (1·6%) pilgrims and other influenza A viruses in eight (2·6%). All the A(H1N1)pdm09 were sensitive to oseltamivir. Conclusions  Only five cases were found to be positive for A(H1N1)pdm09, and it seems unlikely that the arrival of infected pilgrims to their homelands would cause an outbreak of a new wave of infection there. Thus, the low morbidity and mortality rates among the pilgrims could be attributed to the characteristics of A(H1N1)pdm09, which causes morbidity and mortality in a way similar to the seasonal influenza infections, absence of high‐risk individuals among the Iranian pilgrims, and the instructions given to them about contact and hand hygiene, and

  3. No Evidence for Disease History as a Risk Factor for Narcolepsy after A(H1N1)pdm09 Vaccination

    PubMed Central

    Lamb, Favelle; Ploner, Alexander; Fink, Katharina; Maeurer, Markus; Bergman, Peter; Piehl, Fredrik; Weibel, Daniel; Sparén, Pär; Dahlström, Lisen Arnheim

    2016-01-01

    Objectives To investigate disease history before A(H1N1)pdm09 vaccination as a risk factor for narcolepsy. Methods Case-control study in Sweden. Cases included persons referred for a Multiple Sleep Latency Test between 2009 and 2010, identified through diagnostic sleep centres and confirmed through independent review of medical charts. Controls, selected from the total population register, were matched to cases on age, gender, MSLT-referral date and county of residence. Disease history (prescriptions and diagnoses) and vaccination history was collected through telephone interviews and population-based healthcare registers. Conditional logistic regression was used to investigate disease history before A(H1N1)pdm09 vaccination as a risk-factor for narcolepsy. Results In total, 72 narcolepsy cases and 251 controls were included (range 3–69 years mean19-years). Risk of narcolepsy was increased in individuals with a disease history of nervous system disorders (OR range = 3.6–8.8) and mental and behavioural disorders (OR = 3.8, 95% CI 1.6–8.8) before referral. In a second analysis of vaccinated individuals only, nearly all initial associations were no longer statistically significant and effect sizes were smaller (OR range = 1.3–2.6). A significant effect for antibiotics (OR = 0.4, 95% CI 0.2–0.8) and a marginally significant effect for nervous system disorders was observed. In a third case-only analysis, comparing cases referred before vaccination to those referred after; prescriptions for nervous system disorders (OR = 26.0 95% CI 4.0–170.2) and ADHD (OR = 35.3 95% CI 3.4–369.9) were statistically significant during the vaccination period, suggesting initial associations were due to confounding by indication. Conclusion The findings of this study do not support disease history before A(H1N1)pdm09 vaccination as a risk factor for narcolepsy. PMID:27120092

  4. The immunogenicity of the intradermal injection of seasonal trivalent influenza vaccine containing influenza A(H1N1)pdm09 in COPD patients soon after a pandemic.

    PubMed

    Chuaychoo, Benjamas; Kositanont, Uraiwan; Rittayamai, Nuttapol; Niyomthong, Parichat; Songserm, Thaweesak; Maranetra, Khun Nanta; Rattanasaengloet, Kanokwan; Nana, Arth

    2016-07-01

    The antibody responses of a reduced-dose intradermal seasonal influenza vaccination have never been studied in COPD patients soon after a pandemic. A total of 149 COPD patients (60 y of age or older) were randomized to receive trivalent influenza vaccine (Sanofi-Pasteur, France) either 9 µg of hemagglutinin (HA) per strain split into 2-site intradermal (ID) injections via the Mantoux technique or one intramuscular (IM) injection of 15 µg of HA per strain. The geometric mean titers, seroconversion factors, seroconversion rates and seroprotection rates for influenza A(H3N2) and B administered through the ID injection (n = 75) were similar to those obtained with the IM injection (n = 74) 4 weeks post-vaccination. The antibody responses for influenza A(H1N1)pdm09 administered through the ID injection were lower than those obtained with the IM injection, but all of these responses met the 3 criteria proposed by the Committee for Proprietary Medicinal Products (CPMP) for annual re-licensure. The seroprotection rates 4 weeks post-vaccination for influenza A(H1N1)pdm09 were 64.0% (95%CI 52.7-74.0%) in the ID group vs. 78.4% (95% CI 67.6-86.3%) in the IM group (p = 0.053). Influenza-related acute respiratory illness (ARI), diagnosed as a 4-fold rise in HI titers with a convalescent titer > 1:40, and/or the RT-PCR between the ID group (5.3%) and the IM group (8.1%) were not significantly different. The reduced-dose intradermal influenza vaccine may expand vaccine coverage in cases of vaccine shortage. PMID:27153158

  5. Diversity of the murine antibody response targeting influenza A(H1N1pdm09) hemagglutinin

    PubMed Central

    Wilson, Jason R.; Tzeng, Wen-Pin; Spesock, April; Music, Nedzad; Guo, Zhu; Barrington, Robert; Stevens, James; Donis, Ruben O.; Katz, Jacqueline M.; York, Ian A.

    2016-01-01

    We infected mice with the 2009 influenza A pandemic virus (H1N1pdm09), boosted with an inactivated vaccine, and cloned immunoglobulins (Igs) from HA-specific B cells. Based on the redundancy in germline gene utilization, we inferred that between 72–130 unique IgH VDJ and 35 different IgL VJ combinations comprised the anti-HA recall response. The IgH VH1 and IgL VK14 variable gene families were employed most frequently. A representative panel of antibodies were cloned and expressed to confirm reactivity with H1N1pdm09 HA. The majority of the recombinant antibodies were of high avidity and capable of inhibiting H1N1pdm09 hemagglutination. Three of these antibodies were subtype-specific cross-reactive, binding to the HA of A/South Carolina/1/1918(H1N1), and one further reacted with A/swine/Iowa/15/1930(H1N1). These results help define the genetic diversity of the influenza anti-HA antibody repertoire profile induced following infection and vaccination, which may facilitate the development of influenza vaccines that are more protective and broadly neutralizing. Importance Protection against influenza viruses is mediated mainly by antibodies, and in most cases this antibody response is narrow, only providing protection against closely-related viruses. In spite of this limited range of protection, recent findings indicate individuals immune to one influenza virus may contain antibodies (generally a minority of the overall response) that are more broadly reactive. These findings have raised the possibility that influenza vaccines could induce a more broadly protective response, reducing the need for frequent vaccine strain changes. However, interpretation of these observations is hampered by the lack of quantitative characterization of the antibody repertoire. In this study, we used single-cell cloning of influenza HA-specific B cells to assess the diversity and nature of the antibody response to influenza hemagglutinin in mice. Our findings help put bounds on the

  6. Perinatal survival and health after maternal influenza A(H1N1)pdm09 vaccination: A cohort study of pregnancies stratified by trimester of vaccination.

    PubMed

    Baum, Ulrike; Leino, Tuija; Gissler, Mika; Kilpi, Terhi; Jokinen, Jukka

    2015-09-11

    Large cohort studies demonstrated the safety of vaccination with the AS03 adjuvanted pandemic influenza vaccine, but data on first trimester vaccination safety are limited. We conducted a nationwide register-based retrospective cohort study in Finland, included singleton pregnancies present on 01 November 2009 and followed them from 01 November 2009 until delivery. Pregnancies with abortive outcome, pregnancies that started before 01 February 2009 and pregnancies of women, who received the AS03 adjuvanted pandemic influenza vaccine prior to the onset of pregnancy, were excluded. Our main outcome measures were hazard ratios comparing the risk of stillbirth, early neonatal death, moderately preterm birth, very preterm birth, moderately low birth weight, very low birth weight, and being small for gestational age between pregnancies exposed and unexposed to maternal influenza A(H1N1)pdm09 vaccination. The study population comprised 43,604 pregnancies; 34,241 (78.5%) women were vaccinated at some stage during pregnancy. The rates of stillbirth, early neonatal death, moderately preterm birth, and moderately low birth weight were similar between pregnant women exposed and unexposed to influenza A(H1N1)pdm09 vaccination. After adjusting for known risk factors, the relative rates were 0.90 (95% confidence interval 0.55-1.45) for very preterm birth, 0.84 (0.61-1.16) for very low birth weight, and 1.17 (0.98-1.40) for being small for gestational age. Also, in the subanalysis of 7839 women vaccinated during the first trimester, the rates did not indicate that maternal vaccination during the first trimester had any adverse impact on perinatal survival and health. The risk of adverse pregnancy outcomes was not associated with the exposure to the AS03 adjuvanted pandemic influenza vaccine. This study adds reassuring evidence on the safety of AS03 adjuvanted influenza vaccines when given in the first trimester and supports the recommendation of influenza vaccination to all pregnant women through all stages of pregnancy. PMID:26238723

  7. Genetic variants in IL1A and IL1B contribute to the susceptibility to 2009 pandemic H1N1 influenza A virus

    PubMed Central

    2013-01-01

    Background Host genetic variations may contribute to disease susceptibility of influenza. IL-1A and IL-1B are important inflammatory cytokines that mediate the inflammation and initiate the immune response against virus infection. In this study, we investigated the relationship between single-nucleotide polymorphisms (SNPs) of Interleukin-1A (IL-1A) and Interleukin-1B (IL-1B) and the susceptibility to 2009 pandemic A/H1N1 influenza (A(H1N1)pdm09). 167 patients whom were confirmed with A(H1N1)pdm09 and 192 healthy controls were included in this study. Four SNPs (rs1304037, rs16347, rs17561, rs2071373) in IL1A gene and three SNPs (rs1143623, rs3917345, rs1143627) in IL1B gene were genotyped by using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry platform, and the associations of the genetic variants of IL-1 with susceptibility to A(H1N1)pdm09 were then assessed. Results The polymorphisms of rs17561 in IL1A gene and rs1143627 in IL1B gene were found to be associated with susceptibility to A(H1N1)pdm09 with P values of 0.003 (OR 2.08, 95% CI 1.27-3.41) and 0.002 (OR 1.62 , 95% CI 1.20-2.18), respectively. However, no significant difference in allelic frequency was observed for other SNPs between cases and controls. Conclusions This study provides a new insight into pathogenesis of A(H1N1)pdm09, suggesting that genetic variants of IL-1A and IL-1B may exert a substantial impact on the susceptibility of A(H1N1)pdm09 virus infection. PMID:23927441

  8. Efficiency of Points of Dispensing for Influenza A(H1N1)pdm09 Vaccination, Los Angeles County, California, USA, 2009

    PubMed Central

    Dean, Brandon; Teutsch, Steven; Borse, Rebekah H.; Meltzer, Martin I.; Bagwell, DeeAnn; Plough, Alonzo; Fielding, Jonathan

    2014-01-01

    During October 23–December 8, 2009, the Los Angeles County Department of Public Health used points of dispensing (PODs) to improve access to and increase the number of vaccinations against influenza A(H1N1)pdm09. We assessed the efficiency of these units and access to vaccines among ethnic groups. An average of 251 persons per hour (SE 65) were vaccinated at the PODs; a 10% increase in use of live-attenuated monovalent vaccines reduced that rate by 23 persons per hour (SE 7). Vaccination rates were highest for Asians (257/10,000 persons), followed by Hispanics (114/10,000), whites (75/100,000), and African Americans (37/10,000). Average distance traveled to a POD was highest for whites (6.6 miles; SD 6.5) and lowest for Hispanics (4.7 miles; SD ±5.3). Placing PODs in areas of high population density could be an effective strategy to reach large numbers of persons for mass vaccination, but additional PODs may be needed to improve coverage for specific populations. PMID:24656212

  9. The Lao Experience in Deploying Influenza A(H1N1)pdm09 Vaccine: Lessons Made Relevant in Preparing for Present Day Pandemic Threats.

    PubMed

    Xeuatvongsa, Anonh; Mirza, Sara; Winter, Christian; Feldon, Keith; Vongphrachanh, Phengta; Phonekeo, Darouny; Denny, Justin; Khanthamaly, Viengphone; Kounnavong, Bounheuang; Lylianou, Doualy; Phousavath, Sisouphane; Norasingh, Sisouveth; Boutta, Nao; Olsen, Sonja; Bresee, Joseph; Moen, Ann; Corwin, Andrew

    2015-01-01

    The Lao PDR, as did most countries of the Mekong Region, embarked on a pandemic vaccine initiative to counter the threat posed by influenza A(H1N1)pdm09. Overall, estimated vaccine coverage of the Lao population was 14%, with uptake in targeted health care workers and pregnant women 99% and 41%, respectively. Adverse Events Following Immunization accounted for only 6% of survey driven, reported vaccination experiences, with no severe consequences or deaths. Public acceptability of the vaccine campaign was high (98%). Challenges to vaccine deployment included: 1) no previous experience in fielding a seasonal influenza vaccine, 2) safety and efficacy concerns, and 3) late arrival of vaccine 10 months into the pandemic. The Lao success in surmounting these hurdles was in large measure attributed to the oversight assigned the National Immunization Program, and national sensitivities in responding to the avian influenza A(H5N1) crisis in the years leading up to the pandemic. The Lao "lessons learned" from pandemic vaccine deployment are made even more relevant four years on, given the many avian influenza strains circulating in the region, all with pandemic potential. PMID:25923779

  10. Usefulness of health registries when estimating vaccine effectiveness during the influenza A(H1N1)pdm09 pandemic in Norway

    PubMed Central

    2012-01-01

    Background During the 2009-2010 pandemic in Norway, 12 513 laboratory-confirmed cases of pandemic influenza A(H1N1)pdm09, were reported to the Norwegian Surveillance System for Communicable Diseases (MSIS). 2.2 million persons (45% of the population) were vaccinated with an AS03-adjuvanted monovalent vaccine during the pandemic. Most of them were registered in the Norwegian Immunisation Registry (SYSVAK). Based on these registries, we aimed at estimating the vaccine effectiveness (VE) and describing vaccine failures during the pandemic in Norway, in order to evaluate the role of the vaccine as a preventive measure during the pandemic. Methods We conducted a population-based retrospective cohort study, linking MSIS and SYSVAK with pandemic influenza vaccination as exposure and laboratory-confirmed pandemic influenza as outcome. We measured VE by week and defined two thresholds for immunity; eight and 15 days after vaccination. Results The weekly VE ranged from 77% to 96% when considering 15 days or more after vaccination as the threshold of immunity and from 73% to 94% when considering eight days or more. Overall, 157 individuals contracted pandemic influenza eight or more days after vaccination (8.4/100,000 vaccinated), of these 58 had onset 15 days or more after vaccination (3.0/100,000 vaccinated). Most of the vaccine failures occurred during the first weeks of the vaccination campaign. More than 30% of the vaccine failures were found in people below 10 years of age. Conclusions Having available health registries with data regarding cases of specific disease and vaccination makes it feasible to estimate VE in a simple and rapid way. VE was high regardless the immunity threshold chosen. We encourage public health authorities in other countries to set up such registries. It is also important to consider including information on underlying diseases in registries already existing, in order to make it feasible to conduct more complete VE estimations. PMID:22429643

  11. Risk Factors for Death from Influenza A(H1N1)pdm09, State of São Paulo, Brazil, 2009

    PubMed Central

    Ribeiro, Ana Freitas; Pellini, Alessandra Cristina Guedes; Kitagawa, Beatriz Yuko; Marques, Daniel; Madalosso, Geraldine; de Cassia Nogueira Figueira, Gerrita; Fred, João; Albernaz, Ricardo Kerti Mangabeira; Carvalhanas, Telma Regina Marques Pinto; Zanetta, Dirce Maria Trevisan

    2015-01-01

    This case-control study aimed to assess the risk factors for death from influenza A(H1N1)pdm09 in patients with laboratory confirmation, who had severe acute respiratory illness-SARI and were hospitalized between June 28th and August 29th 2009, in the metropolitan regions of São Paulo and Campinas, Brazil. Medical charts of all the 193 patients who died (cases) and the 386 randomly selected patients who recovered (controls) were investigated in 177 hospitals. Household interviews were conducted with those who had survived and the closest relative of those who had died. 73.6% of cases and 38.1% of controls were at risk of developing influenza-related complications. The 18-to-59-year age group (OR = 2.31, 95%CI: 1.31–4.10 (reference up to 18 years of age)), presence of risk conditions for severity of influenza (OR = 1.99, 95%CI: 1.11–3.57, if one or OR = 6.05, 95%CI: 2.76–13.28, if more than one), obesity (OR = 2.73, 95%CI: 1.28–5.83), immunosuppression (OR = 3.43, 95%CI: 1.28–9.19), and search for previous care associated with the hospitalization (OR = 3.35, 95%CI: 1.75–6.40) were risk factors for death. Antiviral treatment performed within 72 hours of the onset of symptoms (OR = 0.17, 95%CI: 0.08–0.37, if within 48hours, and OR = 0.30, 95%CI: 0.11–0.81, if between 48 and 72 hours) was protective against death. The identification of high-risk patients and early treatment are important factors for reducing morbi-mortality from influenza. PMID:25774804

  12. Safety and persistence of the humoral and cellular immune responses induced by 2 doses of an AS03-adjuvanted A(H1N1)pdm09 pandemic influenza vaccine administered to infants, children and adolescents: Two open, uncontrolled studies

    PubMed Central

    Garcia-Sicilia, José; Arístegui, Javier; Omeñaca, Félix; Carmona, Alfonso; Tejedor, Juan C; Merino, José M; García-Corbeira, Pilar; Walravens, Karl; Bambure, Vinod; Moris, Philippe; Caplanusi, Adrian; Gillard, Paul; Dieussaert, Ilse

    2015-01-01

    In children, 2 AS03-adjuvanted A(H1N1)pdm09 vaccine doses given 21 days apart were previously shown to induce a high humoral immune response and to have an acceptable safety profile up to 42 days following the first vaccination. Here, we analyzed the persistence data from 2 open-label studies, which assessed the safety, and humoral and cell-mediated immune responses induced by 2 doses of this vaccine. The first study was a phase II, randomized trial conducted in 104 children aged 6–35 months vaccinated with the A(H1N1)pdm09 vaccine containing 1.9 µg haemagglutinin antigen (HA) and AS03B (5.93 mg tocopherol) and the second study, a phase III, non-randomized trial conducted in 210 children and adolescents aged 3–17 years vaccinated with the A(H1N1)pdm09 vaccine containing 3.75 µg HA and AS03A (11.86 mg tocopherol). Approximately one year after the first dose, all children with available data were seropositive for haemagglutinin inhibition and neutralising antibody titres, but a decline in geometric mean antibody titres was noted. The vaccine induced a cell-mediated immune response in terms of antigen-specific CD4+ T-cells, which persisted up to one year post-vaccination. The vaccine did not raise any safety concern, though these trials were not designed to detect rare events. In conclusion, 2 doses of the AS03-adjuvanted A(H1N1)pdm09 vaccine at 2 different dosages had a clinically acceptable safety profile, and induced high and persistent humoral and cell-mediated immune responses in children aged 6–35 months and 3–17 years. These studies have been registered at www.clinicaltrials.gov NCT00971321 and NCT00964158. PMID:26176592

  13. Review on the impact of pregnancy and obesity on influenza virus infection

    PubMed Central

    Karlsson, Erik A.; Marcelin, Glendie; Webby, Richard J.; Schultz‐Cherry, Stacey

    2012-01-01

    Please cite this paper as: Karlsson et al. (2012) Review on the impact of pregnancy and obesity on influenza virus infection. Influenza and Other Respiratory Viruses 6(6), 449–460. A myriad of risk factors have been linked to an increase in the severity of the pandemic H1N1 2009 influenza A virus [A(H1N1)pdm09] including pregnancy and obesity where death rates can be elevated as compared to the general population. The goal of this review is to provide an overview of the influence of pregnancy and obesity on the reported cases of A(H1N1)pdm09 virus infection and of how the concurrent presence of these factors may have an exacerbating effect on infection outcome. Also, the hypothesized immunologic mechanisms that contribute to A(H1N1)pdm09 virus severity during pregnant or obese states are outlined. Identifying the mechanisms underlying the increased disease severity in these populations may result in improved therapeutic approaches and future pandemic preparedness. PMID:22335790

  14. Post-pandemic influenza A (H1N1) 2009 virus infection in pregnant women in Ceará, Brazil

    PubMed Central

    Perdigão, Anne C B; Araújo, Fernanda M C; Melo, Maria E L; Lemos, Daniele R Q; Cavalcanti, Luciano P; Ramalho, Izabel L C; Araújo, Lia C; Sousa, Deborah M; Siqueira, Marilda M; Guedes, Maria I F

    2015-01-01

    Objective The aim of this study was to present results of the post-pandemic phase of A(H1N1)pdm09 virus infection in pregnant women in Ceará, Brazil, during the January–June 2012 influenza season. Results One hundred and fifty-four nasopharyngeal swab samples were collected from pregnant women admitted to hospitals with suspected severe acute respiratory infection (SARI). Fifty-three (34·4%) had laboratory-confirmed A(H1N1)pdm09 virus infection with 15 (28·3%) outpatients and 38 (71·7%) hospitalized. Five (9·4%) women were in the first trimester of pregnancy, 20 (37·7%) in the second trimester of pregnancy, and 24 (45·2%) in the third trimester of pregnancy. Three had no information about the time of pregnancy. Six samples from newborns were also analyzed, of which three were nasopharyngeal swab positive for A(H1N1)pdm09. These swabs were collected immediately after birth, with the exception of one that was collected on the day after birth. Conclusion Our findings suggest that transplacental transfer of influenza viruses could occur as a result of severe illness in pregnancy. It is therefore important to encourage women to be vaccinated against influenza in order to avoid pregnancy complications. PMID:26290133

  15. Real-time estimation of the hospitalization fatality risk of influenza A(H1N1)pdm09 in Hong Kong.

    PubMed

    Wong, J Y; Wu, P; Lau, E H Y; Tsang, T K; Fang, V J; Ho, L-M; Cowling, B J

    2016-06-01

    During the early stage of an epidemic, timely and reliable estimation of the severity of infections are important for predicting the impact that the influenza viruses will have in the population. We obtained age-specific deaths and hospitalizations for patients with laboratory-confirmed H1N1pdm09 infections from June 2009 to December 2009 in Hong Kong. We retrospectively obtained the real-time estimates of the hospitalization fatality risk (HFR), using crude estimation or allowing for right-censoring for final status in some patients. Models accounting for right-censoring performed better than models without adjustments. The risk of deaths in hospitalized patients with confirmed H1N1pdm09 increased with age. Reliable estimates of the HFR could be obtained before the peak of the first wave of H1N1pdm09 in young and middle-aged adults but after the peak in the elderly. In the next influenza pandemic, timely estimation of the HFR will contribute to risk assessment and disease control. PMID:27125572

  16. Genetic diversity of HA1 domain of heammaglutinin gene of influenza A(H1N1)pdm09 in Tunisia

    PubMed Central

    2013-01-01

    We present major results concerning isolation and determination of the nucleotide sequence of hemagglutinin (HA1) of the pandemic (H1N1)pdm09 influenza viruses found in Tunisia. Amino acid analysis revealed minor amino acid changes in the antigenic or receptor-binding domains. We found mutations that were also present in 1918 pandemic virus, which includes S183P in 4 and S185T mutation in 19 of 27 viruses analyzed from 2011, while none of the 2009 viruses carried these mutations. Also two specific amino acid differences into N-glycosylation sites (N288T and N276H) were detected. The phylogenetic analysis revealed that the majority of the Tunisian isolates clustered with clade A/St. Petersburg/27/2011 viruses characterized by D97N and S185T mutations. However it also reveals a trend of 2010 strains to accumulate amino acid variation and form new phylogenetic clade with three specific amino acid substitutions: V47I, E172K and K308E. PMID:23679923

  17. Modeling Receipt of Influenza A(H1N1)pdm09 Vaccinations among U.S. Children during the 2009-2010 Flu Season: Findings from the 2010 National Health Interview Survey

    PubMed Central

    Blackwell, Debra L.

    2015-01-01

    Objective Using 32 weeks of data from the 2010 National Health Interview Survey, factors associated with receipt of influenza A(H1N1)pdm09 vaccinations among U.S. children during October 2009 through February 2010 are examined. Methods Logistic models estimated receipt of first dose by January 1, 2010 for all children aged 4.5 months through 17 years and receipt of second dose by February 1, 2010 for children aged 6 months through 9 years who received a first dose, using demographic characteristics and measures of family structure, parental education, family income, access to health care, and chronic condition status. All analyses were weighted to yield nationally representative results for the U.S. child population. Results Receipt of a seasonal influenza vaccination in the 12 months prior to October 2009 as well as race/ethnicity, family structure, and various measures representing family socioeconomic status were statistically significant correlates of receipt of the first pH1N1 dose, while children’s asthma and chronic condition status were not. Conclusion In the event of future pandemics, public health officials may utilize these findings to target particular segments of the U.S. child population that may have been underserved during the 2009 influenza pandemic. PMID:25517073

  18. Virological Surveillance of Influenza Viruses during the 2008–09, 2009–10 and 2010–11 Seasons in Tunisia

    PubMed Central

    El Moussi, Awatef; Pozo, Francisco; Ben Hadj Kacem, Mohamed Ali; Ledesma, Juan; Cuevas, Maria Teresa; Casas, Inmaculada; Slim, Amine

    2013-01-01

    Background The data contribute to a better understanding of the circulation of influenza viruses especially in North-Africa. Objective The objective of this surveillance was to detect severe influenza cases, identify their epidemiological and virological characteristics and assess their impact on the healthcare system. Method We describe in this report the findings of laboratory-based surveillance of human cases of influenza virus and other respiratory viruses' infection during three seasons in Tunisia. Results The 2008–09 winter influenza season is underway in Tunisia, with co-circulation of influenza A/H3N2 (56.25%), influenza A(H1N1) (32.5%), and a few sporadic influenza B viruses (11.25%). In 2010–11 season the circulating strains are predominantly the 2009 pandemic influenza A(H1N1)pdm09 (70%) and influenza B viruses (22%). And sporadic viruses were sub-typed as A/H3N2 and unsubtyped influenza A, 5% and 3%, respectively. Unlike other countries, highest prevalence of influenza B virus Yamagata-like lineage has been reported in Tunisia (76%) localised into the clade B/Bangladesh/3333/2007. In the pandemic year, influenza A(H1N1)pdm09 predominated over other influenza viruses (95%). Amino acid changes D222G and D222E were detected in the HA gene of A(H1N1)pdm09 virus in two severe cases, one fatal case and one mild case out of 50 influenza A(H1N1)pdm09 viruses studied. The most frequently reported respiratory virus other than influenza in three seasons was RSV (45.29%). Conclusion This article summarises the surveillance and epidemiology of influenza viruses and other respiratory viruses, showing how rapid improvements in influenza surveillance were feasible by connecting the existing structure in the health care system for patient records to electronic surveillance system for reporting ILI cases. PMID:24069267

  19. Pandemic H1N1 virus transmission and shedding dynamics in index case households of a prospective Vietnamese cohort☆

    PubMed Central

    Thai, Pham Quang; Mai, Le Quynh; Welkers, Matthijs R.A.; Hang, Nguyen Le Khanh; Thanh, Le Thi; Dung, Vu Tien Viet; Yen, Nguyen Thi Thu; Duong, Tran Nhu; Hoa, Le Nguyen Minh; Thoang, Dang Dinh; Trang, Hoang Thi Huyen; de Jong, Menno D.; Wertheim, Heiman; Hien, Nguyen Tran; Horby, Peter; Fox, Annette

    2014-01-01

    Summary Objectives Influenza household transmission studies are required to guide prevention strategies but most passively recruit index cases that seek healthcare. We investigated A(H1N1)pdm09 transmission in a household-based cohort during 2009. Methods Health-workers visited 270 households weekly, and collected swabs from influenza-like-illness cases. If A(H1N1)pdm09 was RT-PCR-confirmed, all household members had symptoms assessed and swabs collected daily for 10–15 days. Viral RNA was quantified and sequenced and serology performed on pre-pandemic sera. Results Index cases were detected in 20 households containing 81 people. 98.5% lacked A(H1N1)pdm09 neutralizing antibodies in pre-pandemic sera. Eleven (18.6%, 95% CI 10.7–30.4%) of 59 contacts were infected. Virus genetic diversity within households was negligible and less than between households. Index and secondary cases were distributed between mothers, daughters and sons, and had similar virus-RNA shedding and symptom dynamics. Fathers were rarely infected. Five secondary cases (45%) had no apparent symptoms and three shed virus before symptoms. Secondary infection was associated with index case wet cough (OR 1.56, 95% CI 1.22–1.99). Conclusions In this cohort of A(H1N1)pdm09 susceptible persons, virus sequencing was capable of discriminating household from community transmission. Household transmission involved mothers and children but rarely fathers. Asymptomatic or pre-symptomatic shedding was common. PMID:24491598

  20. Detection of Novel Reassortant Influenza A (H3N2) and H1N1 2009 Pandemic Viruses in Swine in Hanoi, Vietnam.

    PubMed

    Baudon, E; Poon, L L; Dao, T D; Pham, N T; Cowling, B J; Peyre, M; Nguyen, K V; Peiris, M

    2015-09-01

    From May to September 2013, monthly samples were collected from swine in a Vietnamese slaughterhouse for influenza virus isolation and serological testing. A(H1N1)pdm09 viruses and a novel H3N2 originating from reassortment between A(H1N1)pdm09 and novel viruses of the North American triple reassortant lineage were isolated. Serological results showed low seroprevalence for the novel H3N2 virus and higher seroprevalence for A(H1N1)pdm09 viruses. In addition, serology suggested that other swine influenza viruses are also circulating in Vietnamese swine. PMID:25363845

  1. Quantifying homologous and heterologous antibody titre rises after influenza virus infection.

    PubMed

    Freeman, G; Perera, R A P M; Ngan, E; Fang, V J; Cauchemez, S; Ip, D K M; Peiris, J S M; Cowling, B J

    2016-08-01

    Most influenza virus infections are associated with mild disease. One approach to estimate the occurrence of influenza virus infections in individuals is via repeated measurement of humoral antibody titres. We used baseline and convalescent antibody titres measured by haemagglutination inhibition (HI) and viral neutralization (VN) assays against influenza A(H1N1), A(H3N2) and B viruses to investigate the characteristics of antibody rises following virologically confirmed influenza virus infections in participants in a community-based study. Multivariate models were fitted in a Bayesian framework to characterize the distribution of changes in antibody titres following influenza A virus infections. In 122 participants with PCR-confirmed influenza A virus infection, homologous antibody titres rose by geometric means of 1·2- to 10·2-fold after infection with A(H1N1), A(H3N2) and A(H1N1)pdm09. Significant cross-reactions were observed between A(H1N1)pdm09 and seasonal A(H1N1). Antibody titre rises for some subtypes and assays varied by age, receipt of oseltamivir treatment, and recent receipt of influenza vaccination. In conclusion, we provided a quantitative description of the mean and variation in rises in influenza virus antibody titres following influenza virus infection. The multivariate patterns in boosting of antibody titres following influenza virus infection could be taken into account to improve estimates of cumulative incidence of infection in seroepidemiological studies. PMID:27018720

  2. [Genetic Diversity and Evolution of the M Gene of Human Influenza A Viruses from 2009 to 2013 in Hangzhou, China].

    PubMed

    Shao, Tiejuan; Li, Jun; Pu, Xiaoying; Yu, Xinfen; Kou, Yu; Zhou, Yinyan; Qian, Xin

    2015-03-01

    We investigated the genetic diversity and evolution of the M gene of human influenza A viruses in Hangzhou (Zhejiang province, China) from 2009 to 2013, including subtypes of A(H1N1) pdm09 strains and seasonal A(H3N2) strains. Subtypes of analyzed viruses were identified by cell culture and real-time reverse transcription-polymerase chain reaction, followed by cloning, sequencing and phylogenetic analyses of the M gene. Assessment of 5675 throat swabs revealed a positive rate for the influenza virus of 20.46%, and 827 cases were diagnosed as. infections due to influenza A viruses. Seventy-six influenza-A strains were selected randomly from nine stages during six phases of a virus epidemic. Sequences of the M gene showed high homology among six epidemics with identities of amino-acid sequences of 98.98-100%. All strains contained the adamantine-resistant mutation S31N in its M2 protein. Two of the A(H1N1)pdm09 strains had double mutants of V27A/S31N or V271/S31N. One of the seasonal A(H3N2) viruses had another form of double-mutant R45H/S31N. Evolutionary rate of the M gene was much lower than that of the HA gene and NA gene. Compared with A(H3N2) strains, higher positive pressure on the M1 and M2 proteins of A(H1N1) pdm09 viruses was observed. Separate analyses of M1 and M2 proteins revealed very different selection pressures. Knowledge of the genetic diversity and evolution of the M gene of human influenza-A viruses will be valuable for the control and prevention of diseases. PMID:26164939

  3. Swine Influenza Virus and Association with the Porcine Respiratory Disease Complex in Pig Farms in Southern Brazil.

    PubMed

    Schmidt, C; Cibulski, S P; Andrade, C P; Teixeira, T F; Varela, A P M; Scheffer, C M; Franco, A C; de Almeida, L L; Roehe, P M

    2016-05-01

    Despite the putative endemic status of swine influenza A virus (swIAV) infections, data on the occurrence of swine influenza outbreaks are scarce in Brazil. The aim of this study was to detect and subtype swIAVs from six outbreaks of porcine respiratory disease complex (PRDC) in southern Brazil. Nasal swabs were collected from 66 piglets with signs of respiratory disease in six herds. Lung tissue samples were collected from six necropsied animals. Virus detection was performed by PCR screening and confirmed by virus isolation and hemagglutination (HA). Influenza A subtyping was performed by a real-time reverse transcriptase PCR (rRT-PCR) to detect the A(H1N1)pdm09; other swIAV subtypes were determined by multiplex RT-PCR. In lung tissues, the major bacterial and viral pathogens associated with PRDC (Pasteurella multocida, Mycoplasma hyopneumoniae, Actinobacillus pleuropneumoniae, Haemophilus parasuis and PCV2) were investigated. In some affected pigs, clinico-pathological evaluations were conducted. Influenza A was detected by screening PCR in 46 of 66 swab samples and from five of six lungs. Virus was recovered from pigs of all six herds. Subtype A(H1N1)pdm09 was detected in four of six herds and H1N2 in the other two herds. In lung tissues, further agents involved in PRDC were detected in all cases; Pasteurella multocida was identified in five of six samples and Mycoplasma hyopneumoniae in three of six. Actinobacillus pleuropneumoniae (1/6), Haemophilus parasuis (1/6) and PCV2 (1/6) were also detected. These findings indicate that subtypes A(H1N1)pdm09 and H1N2 were present in pigs in southern Brazil and were associated with PRDC outbreaks. PMID:26302164

  4. Epidemiological and Virological Characteristics of Influenza Viruses Circulating in Cambodia from 2009 to 2011

    PubMed Central

    Ly, Sovann; Heng, Seng; Vong, Sirenda; Kitsutani, Paul; Ieng, Vannra; Tarantola, Arnaud; Ly, Sowath; Sar, Borann; Chea, Nora; Sokhal, Buth; Barr, Ian; Kelso, Anne; Horwood, Paul F.; Timmermans, Ans; Hurt, Aeron; Lon, Chanthap; Saunders, David; Ung, Sam An; Asgari, Nima; Roces, Maria Concepcion; Touch, Sok; Komadina, Naomi; Buchy, Philippe

    2014-01-01

    Background The Cambodian National Influenza Center (NIC) monitored and characterized circulating influenza strains from 2009 to 2011. Methodology/Principal Findings Sentinel and study sites collected nasopharyngeal specimens for diagnostic detection, virus isolation, antigenic characterization, sequencing and antiviral susceptibility analysis from patients who fulfilled case definitions for influenza-like illness, acute lower respiratory infections and event-based surveillance. Each year in Cambodia, influenza viruses were detected mainly from June to November, during the rainy season. Antigenic analysis show that A/H1N1pdm09 isolates belonged to the A/California/7/2009-like group. Circulating A/H3N2 strains were A/Brisbane/10/2007-like in 2009 before drifting to A/Perth/16/2009-like in 2010 and 2011. The Cambodian influenza B isolates from 2009 to 2011 all belonged to the B/Victoria lineage represented by the vaccine strains B/Brisbane/60/2008 and B/Malaysia/2506/2004. Sequences of the M2 gene obtained from representative 2009–2011 A/H3N2 and A/H1N1pdm09 strains all contained the S31N mutation associated with adamantanes resistance except for one A/H1N1pdm09 strain isolated in 2011 that lacked this mutation. No reduction in the susceptibility to neuraminidase inhibitors was observed among the influenza viruses circulating from 2009 to 2011. Phylogenetic analysis revealed that A/H3N2 strains clustered each year to a distinct group while most A/H1N1pdm09 isolates belonged to the S203T clade. Conclusions/Significance In Cambodia, from 2009 to 2011, influenza activity occurred throughout the year with peak seasonality during the rainy season from June to November. Seasonal influenza epidemics were due to multiple genetically distinct viruses, even though all of the isolates were antigenically similar to the reference vaccine strains. The drug susceptibility profile of Cambodian influenza strains revealed that neuraminidase inhibitors would be the drug of choice for

  5. Effectiveness of seasonal influenza vaccinations against laboratory-confirmed influenza-associated infections among Singapore military personnel in 2010–2013

    PubMed Central

    Ho, Hin Peow; Zhao, Xiahong; Pang, Junxiong; Chen, Mark I-C; Lee, Vernon J M; Ang, Li Wei; Lin, Raymond V Tzer Pin; Gao, Christine Q; Hsu, Li Yang; Cook, Alex R

    2014-01-01

    Background Limited information is available about seasonal influenza vaccine effectiveness (VE) in tropical communities. Objectives Virus subtype-specific VE was determined for all military service personnel in the recruit camp and three other non-recruit camp in Singapore's Armed Forces from 1 June 2009 to 30 June 2012. Methods Consenting servicemen underwent nasal washes, which were tested with RT-PCR and subtyped. The test positive case and test negative control design was used to estimate the VE. To estimate the overall effect of the programme on new recruits, we used an ecological time series approach. Results A total of 7016 consultations were collected. The crude estimates for the VE of the triavalent vaccine against both influenza A(H1N1)pdm09 and influenza B were 84% (95% CI 78–88%, 79–86%, respectively). Vaccine efficacy against influenza A(H3N2) was markedly lower (VE 33%, 95% CI −4% to 57%). An estimated 70% (RR = 0·30; 95% CI 0·11–0·84), 39% (RR = 0·61;0·25–1·43) and 75% (RR = 0·25; 95% CI 0·11–0·50) reduction in the risk of influenza A(H1N1)pdm09, influenza A(H3N2) and influenza B infections, respectively, in the recruit camp during the post-vaccination period compared with during the pre-vaccination period was observed. Conclusions Overall, the blanket influenza vaccine programme in Singapore's Armed Forces has had a moderate to high degree of protection against influenza A(H1N1)pdm09 and influenza B, but not against influenza A(H3N2). Blanket influenza vaccination is recommended for all military personnel. PMID:24828687

  6. Pandemic H1N1 influenza virus infection in a Canadian cat.

    PubMed

    Knight, Cameron G; Davies, Jennifer L; Joseph, Tomy; Ondrich, Sarah; Rosa, Brielle V

    2016-05-01

    A cat was presented for necropsy after being found dead at home. Histologic findings suggested viral pneumonia. Polymerase chain reaction and viral typing revealed influenza A(H1N1)pdm09. This is the first report of influenza in a Canadian cat and highlights the importance of considering influenza virus in the differential diagnosis for feline respiratory distress. PMID:27152036

  7. Respiratory viral infections in institutions from late stage of the first and second waves of pandemic influenza A (H1N1) 2009, Ontario, Canada

    PubMed Central

    Asner, Sandra; Peci, Adriana; Marchand‐Austin, Alex; Winter, Anne‐Luise; Olsha, Romy; Kristjanson, Erik; Low, Donald E.; Gubbay, Jonathan B.

    2012-01-01

    Please cite this paper as: Asner et al. (2012) Respiratory viral infections in institutions from late stage of the first and second waves of pandemic A (H1N1) 2009, Ontario, Canada. Influenza and Other Respiratory Viruses 6(3), e11–e15. We report the impact of respiratory viruses on various outbreak settings by using surveillance data from the late first and second wave periods of the 2009 pandemic. A total of 278/345(78·5%) outbreaks tested positive for at least one respiratory virus by multiplex PCR. We detected A(H1N1)pdm09 in 20·6% of all reported outbreaks of which 54·9% were reported by camps, schools, and day cares (CSDs) and 29·6% by long‐term care facilities (LCFTs), whereas enterovirus/human rhinovirus (ENT/HRV) accounted for 62% outbreaks of which 83·7% were reported by long‐term care facilities (LCTFs). ENT/HRV was frequently identified in LTCF outbreaks involving elderly residents, whereas in CSDs, A(H1N1)pdm09 was primarily detected. PMID:22353417

  8. National surveillance for swine influenza virus in the United States, 2009-present

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background and Objectives. In April 2009, a National surveillance plan for swine influenza virus in swine was implemented in the United States. Initial focus of the surveillance was to detect the presence and distribution of viruses (especially the 2009 H1N1 pandemic influenza, A(H1N1)pdm09) that ar...

  9. Detailed Report on 2014/15 Influenza Virus Characteristics, and Estimates on Influenza Virus Vaccine Effectiveness from Austria’s Sentinel Physician Surveillance Network

    PubMed Central

    2016-01-01

    Background Influenza vaccine effectiveness (VE) is influenced by the antigenic similarity between vaccine- and circulating strains. Material and Methods This paper presents data obtained by the Austrian sentinel surveillance system on the evolution of influenza viruses during the season 2014/15 and its impact on influenza vaccine effectiveness in primary care in Austria as estimated by a test-negative case control design. VE estimates were performed for each influenza virus type/subtype, stratified by underlying diseases and adjusted for age, sex and calendar week of infection. Results Detailed genetic and antigenic analyses showed that circulating A(H3N2) viruses were genetically distinct from the 2014/15 A(H3N2) vaccine component indicating a profound vaccine mismatch. The Influenza A(H1N1)pdm09 viruses were antigenically conserved and matched the respective vaccine component. Influenza B viruses were lineage-matched B/Yamagata viruses with a clade-level variation. Consistent with substantial vaccine mismatch for the A(H3N2) viruses a crude overall VE of only 47% was estimated, whereas the VE estimates for A(H1N1)pdm09 were 84% and for influenza B viruses 70%. Increased VE estimates were obtained after stratification by underlying diseases and adjustment for the covariates sex and age, whereby the adjustment for the calendar week of infection was the covariate exerting the highest influence on adjusted VE estimates. Conclusion In summary, VE data obtained in this study underscore the importance to perform VE estimates in the context of detailed characterization of the contributing viruses and also demonstrate that the calendar week of influenza virus infection is the most important confounder of VE estimates. PMID:26975056

  10. Prevalence of gastrointestinal symptoms in patients with influenza, clinical significance, and pathophysiology of human influenza viruses in faecal samples: what do we know?

    PubMed

    Minodier, Laetitia; Charrel, Remi N; Ceccaldi, Pierre-Emmanuel; van der Werf, Sylvie; Blanchon, Thierry; Hanslik, Thomas; Falchi, Alessandra

    2015-01-01

    This review provides for the first time an assessment of the current understanding about the occurrence and the clinical significance of gastrointestinal (GI) symptoms in influenza patients, and their correlation with the presence of human influenza viruses in stools of patients with confirmed influenza virus infection. Studies exploring how human influenza viruses spread to the patient's GI tract after a primary respiratory infection have been summarized. We conducted a systematic search of published peer-reviewed literature up to June 2015 with regard to the above-mentioned aspects, focusing on human influenza viruses (A(H1N1), A(H1N1)pdm09, A(H3N2), and B). Forty-four studies were included in this systematic review and meta-analysis. The pooled prevalence of any digestive symptoms ranged from 30.9% (95% CI, 9.8 to 57.5; I(2) = 97.5%) for A(H1N1)pdm09 to 2.8% (95% CI, 0.6 to 6.5; I(2) = 75.4%) for A(H1N1). The pooled prevalence of influenza viruses in stool was 20.6% (95% CI, 8.9 to 35.5; I(2) = 96.8%), but their correlation with GI symptoms has rarely been explored. The presence of viral RNA in stools because of haematogenous dissemination to organs via infected lymphocytes is likely, but the potential to cause direct intestinal infection and faecal-oral transmission warrants further investigation. This review highlights the gaps in our knowledge, and the high degree of uncertainty about the prevalence and significance of GI symptoms in patients with influenza and their correlation with viral RNA positivity in stool because of the high level of heterogeneity among studies. PMID:26651485

  11. Interval Between Infections and Viral Hierarchy Are Determinants of Viral Interference Following Influenza Virus Infection in a Ferret Model

    PubMed Central

    Laurie, Karen L.; Guarnaccia, Teagan A.; Carolan, Louise A.; Yan, Ada W. C.; Aban, Malet; Petrie, Stephen; Cao, Pengxing; Heffernan, Jane M.; McVernon, Jodie; Mosse, Jennifer; Kelso, Anne; McCaw, James M.; Barr, Ian G.

    2015-01-01

    Background. Epidemiological studies suggest that, following infection with influenza virus, there is a short period during which a host experiences a lower susceptibility to infection with other influenza viruses. This viral interference appears to be independent of any antigenic similarities between the viruses. We used the ferret model of human influenza to systematically investigate viral interference. Methods. Ferrets were first infected then challenged 1–14 days later with pairs of influenza A(H1N1)pdm09, influenza A(H3N2), and influenza B viruses circulating in 2009 and 2010. Results. Viral interference was observed when the interval between initiation of primary infection and subsequent challenge was <1 week. This effect was virus specific and occurred between antigenically related and unrelated viruses. Coinfections occurred when 1 or 3 days separated infections. Ongoing shedding from the primary virus infection was associated with viral interference after the secondary challenge. Conclusions. The interval between infections and the sequential combination of viruses were important determinants of viral interference. The influenza viruses in this study appear to have an ordered hierarchy according to their ability to block or delay infection, which may contribute to the dominance of different viruses often seen in an influenza season. PMID:25943206

  12. Intermonomer Interactions in Hemagglutinin Subunits HA1 and HA2 Affecting Hemagglutinin Stability and Influenza Virus Infectivity

    PubMed Central

    DeFeo, Christopher J.; Alvarado-Facundo, Esmeralda; Vassell, Russell

    2015-01-01

    ABSTRACT Influenza virus hemagglutinin (HA) mediates virus entry by binding to cell surface receptors and fusing the viral and endosomal membranes following uptake by endocytosis. The acidic environment of endosomes triggers a large-scale conformational change in the transmembrane subunit of HA (HA2) involving a loop (B loop)-to-helix transition, which releases the fusion peptide at the HA2 N terminus from an interior pocket within the HA trimer. Subsequent insertion of the fusion peptide into the endosomal membrane initiates fusion. The acid stability of HA is influenced by residues in the fusion peptide, fusion peptide pocket, coiled-coil regions of HA2, and interactions between the surface (HA1) and HA2 subunits, but details are not fully understood and vary among strains. Current evidence suggests that the HA from the circulating pandemic 2009 H1N1 influenza A virus [A(H1N1)pdm09] is less stable than the HAs from other seasonal influenza virus strains. Here we show that residue 205 in HA1 and residue 399 in the B loop of HA2 (residue 72, HA2 numbering) in different monomers of the trimeric A(H1N1)pdm09 HA are involved in functionally important intermolecular interactions and that a conserved histidine in this pair helps regulate HA stability. An arginine-lysine pair at this location destabilizes HA at acidic pH and mediates fusion at a higher pH, while a glutamate-lysine pair enhances HA stability and requires a lower pH to induce fusion. Our findings identify key residues in HA1 and HA2 that interact to help regulate H1N1 HA stability and virus infectivity. IMPORTANCE Influenza virus hemagglutinin (HA) is the principal antigen in inactivated influenza vaccines and the target of protective antibodies. However, the influenza A virus HA is highly variable, necessitating frequent vaccine changes to match circulating strains. Sequence changes in HA affect not only antigenicity but also HA stability, which has important implications for vaccine production, as well

  13. Influenza A Viruses of Human Origin in Swine, Brazil.

    PubMed

    Nelson, Martha I; Schaefer, Rejane; Gava, Danielle; Cantão, Maurício Egídio; Ciacci-Zanella, Janice Reis

    2015-08-01

    The evolutionary origins of the influenza A(H1N1)pdm09 virus that caused the first outbreak of the 2009 pandemic in Mexico remain unclear, highlighting the lack of swine surveillance in Latin American countries. Although Brazil has one of the largest swine populations in the world, influenza was not thought to be endemic in Brazil's swine until the major outbreaks of influenza A(H1N1)pdm09 in 2009. Through phylogenetic analysis of whole-genome sequences of influenza viruses of the H1N1, H1N2, and H3N2 subtypes collected in swine in Brazil during 2009-2012, we identified multiple previously uncharacterized influenza viruses of human seasonal H1N2 and H3N2 virus origin that have circulated undetected in swine for more than a decade. Viral diversity has further increased in Brazil through reassortment between co-circulating viruses, including A(H1N1)pdm09. The circulation of multiple divergent hemagglutinin lineages challenges the design of effective cross-protective vaccines and highlights the need for additional surveillance. PMID:26196759

  14. Influenza A Viruses of Human Origin in Swine, Brazil

    PubMed Central

    Schaefer, Rejane; Gava, Danielle; Cantão, Maurício Egídio; Ciacci-Zanella, Janice Reis

    2015-01-01

    The evolutionary origins of the influenza A(H1N1)pdm09 virus that caused the first outbreak of the 2009 pandemic in Mexico remain unclear, highlighting the lack of swine surveillance in Latin American countries. Although Brazil has one of the largest swine populations in the world, influenza was not thought to be endemic in Brazil’s swine until the major outbreaks of influenza A(H1N1)pdm09 in 2009. Through phylogenetic analysis of whole-genome sequences of influenza viruses of the H1N1, H1N2, and H3N2 subtypes collected in swine in Brazil during 2009–2012, we identified multiple previously uncharacterized influenza viruses of human seasonal H1N2 and H3N2 virus origin that have circulated undetected in swine for more than a decade. Viral diversity has further increased in Brazil through reassortment between co-circulating viruses, including A(H1N1)pdm09. The circulation of multiple divergent hemagglutinin lineages challenges the design of effective cross-protective vaccines and highlights the need for additional surveillance. PMID:26196759

  15. Respiratory viral infections in institutions from late stage of the first and second waves of pandemic influenza A (H1N1) 2009, Ontario, Canada.

    PubMed

    Asner, Sandra; Peci, Adriana; Marchand-Austin, Alex; Winter, Anne-Luise; Olsha, Romy; Kristjanson, Erik; Low, Donald E; Gubbay, Jonathan B

    2012-05-01

    We report the impact of respiratory viruses on various outbreak settings by using surveillance data from the late first and second wave periods of the 2009 pandemic. A total of 278/345(78·5%) outbreaks tested positive for at least one respiratory virus by multiplex PCR. We detected A(H1N1)pdm09 in 20·6% of all reported outbreaks of which 54·9% were reported by camps, schools, and day cares (CSDs) and 29·6% by long-term care facilities (LCFTs), whereas enterovirus/human rhinovirus (ENT/HRV) accounted for 62% outbreaks of which 83·7% were reported by long-term care facilities (LCTFs). ENT/HRV was frequently identified in LTCF outbreaks involving elderly residents, whereas in CSDs, A(H1N1)pdm09 was primarily detected. PMID:22353417

  16. Intensive care unit surveillance of influenza infection in France: the 2009/10 pandemic and the three subsequent seasons.

    PubMed

    Bonmarin, Isabelle; Belchior, Emmanuel; Bergounioux, Jean; Brun-Buisson, Christian; Mégarbane, Bruno; Chappert, Jean Loup; Hubert, Bruno; Le Strat, Yann; Lévy-Bruhl, Daniel

    2015-01-01

    During the 2009/10 pandemic, a national surveillance system for severe influenza cases was set up in France. We present results from the system's first four years. All severe influenza cases admitted to intensive care units (ICU) were reported to the Institut de Veille Sanitaire using a standardised form: data on demographics, immunisation and virological status, risk factors, severity (e.g. acute respiratory distress syndrome (ARDS) onset, mechanical ventilation, extracorporeal life support) and outcome. Multivariate analysis was performed to identify factors associated with ARDS and death. The number of confirmed influenza cases varied from 1,210 in 2009/10 to 321 in 2011/12. Most ICU patients were infected with A(H1N1)pdm09, except during the 2011/12 winter season when A(H3N2)-related infections predominated. Patients' characteristics varied according to the predominant strain. Based on multivariate analysis, risk factors associated with death were age ≥ 65 years, patients with any of the usual recommended indications for vaccination and clinical severity. ARDS occurred more frequently in patients who were middle-aged (36-55 years), pregnant, obese, or infected with A(H1N1)pdm09. Female sex and influenza vaccination were protective. These data confirm the persistent virulence of A(H1N1)pdm09 after the pandemic and the heterogeneity of influenza seasons, and reinforce the need for surveillance of severe influenza cases. PMID:26607262

  17. Characterization of the Localized Immune Response in the Respiratory Tract of Ferrets following Infection with Influenza A and B Viruses

    PubMed Central

    Carolan, Louise A.; Rockman, Steve; Borg, Kathryn; Guarnaccia, Teagan; Reading, Patrick; Mosse, Jennifer; Kelso, Anne; Barr, Ian

    2015-01-01

    ABSTRACT The burden of infection with seasonal influenza viruses is significant. Each year is typically characterized by the dominance of one (sub)type or lineage of influenza A or B virus, respectively. The incidence of disease varies annually, and while this may be attributed to a particular virus strain or subtype, the impacts of prior immunity, population differences, and variations in clinical assessment are also important. To improve our understanding of the impacts of seasonal influenza viruses, we directly compared clinical symptoms, virus shedding, and expression of cytokines, chemokines, and immune mediators in the upper respiratory tract (URT) of ferrets infected with contemporary A(H1N1)pdm09, A(H3N2), or influenza B virus. Gene expression in the lower respiratory tract (LRT) was also assessed. Clinical symptoms were minimal. Overall cytokine/chemokine profiles in the URT were consistent in pattern and magnitude between animals infected with influenza A and B viruses, and peak expression levels of interleukin-1α (IL-1α), IL-1β, IL-6, IL-12p40, alpha interferon (IFN-α), IFN-β, and tumor necrosis factor alpha (TNF-α) mRNAs correlated with peak levels of viral shedding. MCP1 and IFN-γ were expressed after the virus peak. Granzymes A and B and IL-10 reached peak expression as the virus was cleared and seroconversion was detected. Cytokine/chemokine gene expression in the LRT following A(H1N1)pdm09 virus infection reflected the observations seen for the URT but was delayed 2 or 3 days, as was virus replication. These data indicate that disease severities and localized immune responses following infection with seasonal influenza A and B viruses are similar, suggesting that other factors are likely to modulate the incidence and impact of seasonal influenza. IMPORTANCE Both influenza A and B viruses cocirculate in the human population, and annual influenza seasons are typically dominated by an influenza A virus subtype or an influenza B virus lineage

  18. Comparable Fitness and Transmissibility between Oseltamivir-Resistant Pandemic 2009 and Seasonal H1N1 Influenza Viruses with the H275Y Neuraminidase Mutation

    PubMed Central

    Wong, Diana D. Y.; Choy, Ka-Tim; Chan, Renee W. Y.; Sia, Sin Fun; Chiu, Hsin-Ping; Cheung, Peter P. H.; Chan, Michael C. W.

    2012-01-01

    Limited antiviral compounds are available for the control of influenza, and the emergence of resistant variants would further narrow the options for defense. The H275Y neuraminidase (NA) mutation, which confers resistance to oseltamivir carboxylate, has been identified among the seasonal H1N1 and 2009 pandemic influenza viruses; however, those H275Y resistant variants demonstrated distinct epidemiological outcomes in humans. Specifically, dominance of the H275Y variant over the oseltamivir-sensitive viruses was only reported for a seasonal H1N1 variant during 2008-2009. Here, we systematically analyze the effect of the H275Y NA mutation on viral fitness and transmissibility of A(H1N1)pdm09 and seasonal H1N1 influenza viruses. The NA genes from A(H1N1)pdm09 A/California/04/09 (CA04), seasonal H1N1 A/New Caledonia/20/1999 (NewCal), and A/Brisbane/59/2007 (Brisbane) were individually introduced into the genetic background of CA04. The H275Y mutation led to reduced NA enzyme activity, an increased Km for 3′-sialylactose or 6′-sialylactose, and decreased infectivity in mucin-secreting human airway epithelial cells compared to the oseltamivir-sensitive wild-type counterparts. Attenuated pathogenicity in both RG-CA04NA-H275Y and RG-CA04 × BrisbaneNA-H275Y viruses was observed in ferrets compared to RG-CA04 virus, although the transmissibility was minimally affected. In parallel experiments using recombinant Brisbane viruses differing by hemagglutinin and NA, comparable direct contact and respiratory droplet transmissibilities were observed among RG-NewCalHA,NA, RG-NewCalHA,NA-H275Y, RG-BrisbaneHA,NA-H275Y, and RG-NewCalHA × BrisbaneNA-H275Y viruses. Our results demonstrate that, despite the H275Y mutation leading to a minor reduction in viral fitness, the transmission potentials of three different antigenic strains carrying this mutation were comparable in the naïve ferret model. PMID:22811535

  19. Characterization of drug-resistant influenza virus A(H1N1) and A(H3N2) variants selected in vitro with laninamivir.

    PubMed

    Samson, Mélanie; Abed, Yacine; Desrochers, François-Marc; Hamilton, Stephanie; Luttick, Angela; Tucker, Simon P; Pryor, Melinda J; Boivin, Guy

    2014-09-01

    Neuraminidase inhibitors (NAIs) play a major role for managing influenza virus infections. The widespread oseltamivir resistance among 2007-2008 seasonal A(H1N1) viruses and community outbreaks of oseltamivir-resistant A(H1N1)pdm09 strains highlights the need for additional anti-influenza virus agents. Laninamivir is a novel long-lasting NAI that has demonstrated in vitro activity against influenza A and B viruses, and its prodrug (laninamivir octanoate) is in phase II clinical trials in the United States and other countries. Currently, little information is available on the mechanisms of resistance to laninamivir. In this study, we first performed neuraminidase (NA) inhibition assays to determine the activity of laninamivir against a set of influenza A viruses containing NA mutations conferring resistance to one or many other NAIs. We also generated drug-resistant A(H1N1) and A(H3N2) viruses under in vitro laninamivir pressure. Laninamivir demonstrated a profile of susceptibility that was similar to that of zanamivir. More specifically, it retained activity against oseltamivir-resistant H275Y and N295S A(H1N1) variants and the E119V A(H3N2) variant. In vitro, laninamivir pressure selected the E119A NA substitution in the A/Solomon Islands/3/2006 A(H1N1) background, whereas E119K and G147E NA changes along with a K133E hemagglutinin (HA) substitution were selected in the A/Quebec/144147/2009 A(H1N1)pdm09 strain. In the A/Brisbane/10/2007 A(H3N2) background, a large NA deletion accompanied by S138A/P194L HA substitutions was selected. This H3N2 variant had altered receptor-binding properties and was highly resistant to laninamivir in plaque reduction assays. Overall, we confirmed the similarity between zanamivir and laninamivir susceptibility profiles and demonstrated that both NA and HA changes can contribute to laninamivir resistance in vitro. PMID:24957832

  20. On Temporal Patterns and Circulation of Influenza Virus Strains in Taiwan, 2008-2014: Implications of 2009 pH1N1 Pandemic

    PubMed Central

    Hsieh, Ying-Hen; Huang, Hsiang-Min; Lan, Yu-Ching

    2016-01-01

    Background It has been observed that, historically, strains of pandemic influenza led to succeeding seasonal waves, albeit with decidedly different patterns. Recent studies suggest that the 2009 A(H1N1)pdm09 pandemic has had an impact on the circulation patterns of seasonal influenza strains in the post-pandemic years. In this work we aim to investigate this issue and also to compare the relative transmissibility of these waves of differing strains using Taiwan influenza surveillance data before, during and after the pandemic. Methods We make use of the Taiwan Center for Disease Control and Prevention influenza surveillance data on laboratory-confirmed subtyping of samples and a mathematical model to determine the waves of circulating (and co-circulating) H1, H3 and B virus strains in Taiwan during 2008–2014; or namely, short before, during and after the 2009 pandemic. We further pinpoint the turning points and relative transmissibility of each wave, in order to ascertain whether any temporal pattern exists. Results/Findings For two consecutive years following the 2009 pandemic, A(H1N1)pdm09 circulated in Taiwan (as in most of Northern Hemisphere), sometimes co-circulating with AH3. From the evolution point of view, A(H1N1)pdm09 and AH3 were able to sustain their circulation patterns to the end of 2010. In fact, A(H1N1)pdm09 virus circulated in six separate waves in Taiwan between summer of 2009 and spring of 2014. Since 2009, a wave of A(H1N1)pmd09 occurred every fall/winter influenza season during our study period except 2011–2012 season, when mainly influenza strain B circulated. In comparing transmissibility, while the estimated per capita weekly growth rates for cumulative case numbers (and the reproduction number) seem to be lower for most of the influenza B waves (0.06~0.26; range of 95% CIs: 0.05~0.32) when compared to those of influenza A, the wave of influenza B from week 8 to week 38 of 2010 immediately following the fall/winter wave of 2009 A(H1N1

  1. Global update on the susceptibility of human influenza viruses to neuraminidase inhibitors, 2014-2015.

    PubMed

    Hurt, Aeron C; Besselaar, Terry G; Daniels, Rod S; Ermetal, Burcu; Fry, Alicia; Gubareva, Larisa; Huang, Weijuan; Lackenby, Angie; Lee, Raphael T C; Lo, Janice; Maurer-Stroh, Sebastian; Nguyen, Ha T; Pereyaslov, Dmitriy; Rebelo-de-Andrade, Helena; Siqueira, Marilda M; Takashita, Emi; Tashiro, Masato; Tilmanis, Danielle; Wang, Dayan; Zhang, Wenqing; Meijer, Adam

    2016-08-01

    The World Health Organization (WHO) Collaborating Centres for Reference and Research on Influenza (WHO CCs) tested 13,312 viruses collected by WHO recognized National Influenza Centres between May 2014 and May 2015 to determine 50% inhibitory concentration (IC50) data for neuraminidase inhibitors (NAIs) oseltamivir, zanamivir, peramivir and laninamivir. Ninety-four per cent of the viruses tested by the WHO CCs were from three WHO regions: Western Pacific, the Americas and Europe. Approximately 0.5% (n = 68) of viruses showed either highly reduced inhibition (HRI) or reduced inhibition (RI) (n = 56) against at least one of the four NAIs. Of the twelve viruses with HRI, six were A(H1N1)pdm09 viruses, three were A(H3N2) viruses and three were B/Yamagata-lineage viruses. The overall frequency of viruses with RI or HRI by the NAIs was lower than that observed in 2013-14 (1.9%), but similar to the 2012-13 period (0.6%). Based on the current analysis, the NAIs remain an appropriate choice for the treatment and prophylaxis of influenza virus infections. PMID:27265623

  2. The East Jakarta Project: surveillance for highly pathogenic avian influenza A(H5N1) and seasonal influenza viruses in patients seeking care for respiratory disease, Jakarta, Indonesia, October 2011-September 2012.

    PubMed

    Storms, A D; Kusriastuti, R; Misriyah, S; Praptiningsih, C Y; Amalya, M; Lafond, K E; Samaan, G; Triada, R; Iuliano, A D; Ester, M; Sidjabat, R; Chittenden, K; Vogel, R; Widdowson, M A; Mahoney, F; Uyeki, T M

    2015-12-01

    Indonesia has reported the most human infections with highly pathogenic avian influenza (HPAI) A(H5N1) virus worldwide. We implemented enhanced surveillance in four outpatient clinics and six hospitals for HPAI H5N1 and seasonal influenza viruses in East Jakarta district to assess the public health impact of influenza in Indonesia. Epidemiological and clinical data were collected from outpatients with influenza-like illness (ILI) and hospitalized patients with severe acute respiratory infection (SARI); respiratory specimens were obtained for influenza testing by real-time reverse transcription-polymerase chain reaction. During October 2011-September 2012, 1131/3278 specimens from ILI cases (34·5%) and 276/1787 specimens from SARI cases (15·4%) tested positive for seasonal influenza viruses. The prevalence of influenza virus infections was highest during December-May and the proportion testing positive was 76% for ILI and 36% for SARI during their respective weeks of peak activity. No HPAI H5N1 virus infections were identified, including hundreds of ILI and SARI patients with recent poultry exposures, whereas seasonal influenza was an important contributor to acute respiratory disease in East Jakarta. Overall, 668 (47%) of influenza viruses were influenza B, 384 (27%) were A(H1N1)pdm09, and 359 (25%) were H3. While additional data over multiple years are needed, our findings suggest that seasonal influenza prevention efforts, including influenza vaccination, should target the months preceding the rainy season. PMID:25912029

  3. A Case of Long-Term Seronegative Human Immunodeficiency Virus (HIV) Infection: The Importance of the Humoral Response to HIV

    PubMed Central

    Siemieniuk, Reed A. C.; van der Meer, Frank; van Marle, Guido; Gill, M. John

    2016-01-01

    Background. Seronegative human immunodeficiency virus (HIV) infections are exceedingly rare but might inform HIV-host physiology. Methods. We investigate the cause and consequences of a patient infected with HIV who did not mount a humoral response to HIV for 4 years. Results. The patient was confirmed HIV-uninfected by nucleic acid testing 4 months before rapidly progressing to acquired immune deficiency syndrome. The patient's humoral deficit was specific to HIV: he mounted robust humoral responses to all challenge vaccines including influenza A(H1N1)pdm09 and all T cell-dependent and -independent serotypes in the 23-valent pneumococcal polysaccharide vaccine. The virus had similar gp120 antigenicity to HIV-positive control serum as NL4-3 and YU2 prototype strains. Two human leukocyte antigen alleles associated with rapid progression were identified (B*08 and B*35), and a cytotoxic T-lymphocyte epitope site variant was noted: E277K. Viral decay (t1/2 ≈ 39 weeks) suggested that relatively long-lived cells were the source of ongoing viremia. Human immunodeficiency virus viremia was not suppressed until after the patient developed a humoral immune response, despite therapeutic antiretroviral levels. No resistance was detected by virtual phenotyping of virus obtained from serum or from gastrointestinal biopsies despite considerable antiretroviral selection pressure. Conclusions. Ineffective antibody production may be associated with a subgroup of extremely rapid HIV progressors. Although antiretroviral therapy may be sufficient to slow propagation of infection, it appears to be ineffective for HIV viral clearance in the absence of a humoral response. PMID:26858962

  4. Evaluation of a dry powder delivery system for laninamivir in a ferret model of influenza infection.

    PubMed

    Panozzo, Jacqueline; Oh, Ding Yuan; Margo, Kenneth; Morton, David A; Piedrafita, David; Mosse, Jennifer; Hurt, Aeron C

    2015-08-01

    Laninamivir is a long-acting antiviral requiring only a single dose for the treatment of influenza infection, making it an attractive alternative to existing neuraminidase inhibitors that require multiple doses over many days. Like zanamivir, laninamivir is administered to patients by inhalation of dry powder. To date, studies investigating the effectiveness of laninamivir or zanamivir in a ferret model of influenza infection have administered the drug in a solubilised form. To better mimic the delivery action of laninamivir in humans, we assessed the applicability of a Dry Powder Insufflator™ (DPI) as a delivery method for laninamivir octanoate (LO) in ferrets to determine the effectiveness of this drug in reducing influenza A and B virus infections. In vitro characterisation of the DPI showed that both the small particle sized LO (0.7-6.0μm diameter) and the large particle sized lactose carrier (20-100μm diameter) were effectively discharged. However, LO delivered to ferrets via the DPI prior to infection with either A(H1N1)pdm09 or B viruses had a limited effect on nasal inflammation, clinical symptoms and viral shedding compared to placebo. Our preliminary findings indicate the feasibility of administering powder drugs into ferrets, but a better understanding of the pharmacokinetics and pharmacodynamics of LO in ferrets following delivery by the DPI is warranted prior to further studies. PMID:26022199

  5. Implementing hospital-based surveillance for severe acute respiratory infections caused by influenza and other respiratory pathogens in New Zealand

    PubMed Central

    Baker, Michael; McArthur, Colin; Roberts, Sally; Williamson, Deborah; Grant, Cameron; Trenholme, Adrian; Wong, Conroy; Taylor, Susan; LeComte, Lyndsay; Mackereth, Graham; Bandaranayake, Don; Wood, Tim; Bissielo, Ange; Se, Ruth; Turner, Nikki; Pierse, Nevil; Thomas, Paul; Webby, Richard; Gross, Diane; Duque, Jazmin; Thompson, Mark; Widdowson, Marc-Alain

    2014-01-01

    Background Recent experience with pandemic influenza A(H1N1)pdm09 highlighted the importance of global surveillance for severe respiratory disease to support pandemic preparedness and seasonal influenza control. Improved surveillance in the southern hemisphere is needed to provide critical data on influenza epidemiology, disease burden, circulating strains and effectiveness of influenza prevention and control measures. Hospital-based surveillance for severe acute respiratory infection (SARI) cases was established in New Zealand on 30 April 2012. The aims were to measure incidence, prevalence, risk factors, clinical spectrum and outcomes for SARI and associated influenza and other respiratory pathogen cases as well as to understand influenza contribution to patients not meeting SARI case definition. Methods/Design All inpatients with suspected respiratory infections who were admitted overnight to the study hospitals were screened daily. If a patient met the World Health Organization’s SARI case definition, a respiratory specimen was tested for influenza and other respiratory pathogens. A case report form captured demographics, history of presenting illness, co-morbidities, disease course and outcome and risk factors. These data were supplemented from electronic clinical records and other linked data sources. Discussion Hospital-based SARI surveillance has been implemented and is fully functioning in New Zealand. Active, prospective, continuous, hospital-based SARI surveillance is useful in supporting pandemic preparedness for emerging influenza A(H7N9) virus infections and seasonal influenza prevention and control. PMID:25077034

  6. Genetic Characterization of H1N1 and H1N2 Influenza A Viruses Circulating in Ontario Pigs in 2012

    PubMed Central

    Grgić, Helena; Costa, Marcio; Friendship, Robert M.; Carman, Susy; Nagy, Éva; Poljak, Zvonimir

    2015-01-01

    The objective of this study was to characterize H1N1 and H1N2 influenza A virus isolates detected during outbreaks of respiratory disease in pig herds in Ontario (Canada) in 2012. Six influenza viruses were included in analysis using full genome sequencing based on the 454 platform. In five H1N1 isolates, all eight segments were genetically related to 2009 pandemic virus (A(H1N1)pdm09). One H1N2 isolate had hemagglutinin (HA), polymerase A (PA) and non-structural (NS) genes closely related to A(H1N1)pdm09, and neuraminidase (NA), matrix (M), polymerase B1 (PB1), polymerase B2 (PB2), and nucleoprotein (NP) genes originating from a triple-reassortant H3N2 virus (tr H3N2). The HA gene of five Ontario H1 isolates exhibited high identity of 99% with the human A(H1N1)pdm09 [A/Mexico/InDRE4487/09] from Mexico, while one Ontario H1N1 isolate had only 96.9% identity with this Mexican virus. Each of the five Ontario H1N1 viruses had between one and four amino acid (aa) changes within five antigenic sites, while one Ontario H1N2 virus had two aa changes within two antigenic sites. Such aa changes in antigenic sites could have an effect on antibody recognition and ultimately have implications for immunization practices. According to aa sequence analysis of the M2 protein, Ontario H1N1 and H1N2 viruses can be expected to offer resistance to adamantane derivatives, but not to neuraminidase inhibitors. PMID:26030614

  7. Neuraminidase inhibitor susceptibility profile of pandemic and seasonal influenza viruses during the 2009-2010 and 2010-2011 influenza seasons in Japan.

    PubMed

    Dapat, Clyde; Kondo, Hiroki; Dapat, Isolde C; Baranovich, Tatiana; Suzuki, Yasushi; Shobugawa, Yugo; Saito, Kousuke; Saito, Reiko; Suzuki, Hiroshi

    2013-09-01

    Two new influenza virus neuraminidase inhibitors (NAIs), peramivir and laninamivir, were approved in 2010 which resulted to four NAIs that were used during the 2010-2011 influenza season in Japan. This study aims to monitor the susceptibility of influenza virus isolates in 2009-2010 and 2010-2011 influenza seasons in Japan to the four NAIs using the fluorescence-based 50% inhibitory concentration (IC₅₀) method. Outliers were identified using box-and-whisker plot analysis and full NA gene sequencing was performed to determine the mutations that are associated with reduction of susceptibility to NAIs. A total of 117 influenza A(H1N1)pdm09, 59 A(H3N2), and 18 type B viruses were tested before NAI treatment and eight A(H1N1)pdm09 and 1 type B viruses were examined from patients after NAI treatment in the two seasons. NA inhibition assay showed type A influenza viruses were more susceptible to NAIs than type B viruses. The peramivir and laninamivir IC₅₀ values of both type A and B viruses were significantly lower than the oseltamivir and zanamivir IC₅₀ values. Among influenza A(H1N1)pdm09 viruses, the prevalence of H274Y viruses increased from 0% in the 2009-2010 season to 3% in the 2010-2011 season. These H274Y viruses were resistant to oseltamivir and peramivir with 200-300 fold increase in IC₅₀ values but remained sensitive to zanamivir and laninamivir. Other mutations in NA, such as I222T and M241I were identified among the outliers. Among influenza A(H3N2) viruses, two outliers were identified with D151G and T148I mutations, which exhibited a reduction in susceptibility to oseltamivir and zanamivir, respectively. Among type B viruses, no outliers were identified to the four NAIs. For paired samples that were collected before and after drug treatment, three (3/11; 27.3%) H274Y viruses were identified among A(H1N1)pdm09 viruses after oseltamivir treatment but no outliers were found in the laninamivir-treatment group (n=3). Despite widespread use of

  8. Influenza virus surveillance in Argentina during the 2012 season: antigenic characterization, genetic analysis and antiviral susceptibility.

    PubMed

    Benedetti, E; Daniels, R S; Pontoriero, A; Russo, M; Avaro, M; Czech, A; Campos, A; Periolo, N; Gregory, V; McCauley, J W; Baumeister, E G

    2016-03-01

    The activity and circulation of influenza viruses in Argentina was studied during 2012 as part of the Argentinean Surveillance for Influenza and other Respiratory Viruses, in the context of Global Influenza Surveillance. The antigenicity and molecular characteristics of haemagglutinins (HA) of circulating influenza A and B viruses were analysed to assess the emergence of virus variants. Susceptibility to oseltamivir and zanamivir was evaluated by enzymatic assay and results were backed-up by sequencing of the neuraminidase (NA) genes. During the 2012 season, influenza virus circulation in Argentina was detected from weeks 24 to 51. The HA sequences of the studied A(H1N1)pdm09 subtype viruses segregated in a different genetic group compared to those identified during the 2009 pandemic, although they were still closely related antigenically to the vaccine virus A/California/07/2009. The HA sequences of the A(H3N2) viruses analysed fell into the A/Victoria/208/2009 clade, genetic group 3C. A mixed circulation of virus variants belonging to B/Victoria and B/Yamagata lineages was detected, with B/Victoria being dominant. All viruses tested were sensitive to oseltamivir and zanamivir except one. This isolate, an A(H1N1)pdm09 virus possessing the substitution NA-N295S, showed highly reduced inhibition by oseltamivir and reduced inhibition by zanamivir. Virological and epidemiological surveillance remains critical for detection of evolving influenza viruses. PMID:26345289

  9. Viral Pneumonitis Is Increased in Obese Patients during the First Wave of Pandemic A(H1N1) 2009 Virus

    PubMed Central

    Kok, Jen; Blyth, Christopher C.; Foo, Hong; Bailey, Michael J.; Pilcher, David V.; Webb, Steven A.; Seppelt, Ian M.; Dwyer, Dominic E.; Iredell, Jonathan R.

    2013-01-01

    Introduction There is conflicting data as to whether obesity is an independent risk factor for mortality in severe pandemic (H1N1) 2009 influenza (A(H1N1)pdm09). It is postulated that excess inflammation and cytokine production in obese patients following severe influenza infection leads to viral pneumonitis and/or acute respiratory distress syndrome. Methods Demographic, laboratory and clinical data prospectively collected from obese and non-obese patients admitted to nine adult Australian intensive care units (ICU) during the first A(H1N1)pdm09 wave, supplemented with retrospectively collected data, were compared. Results Of 173 patients, 100 (57.8%), 73 (42.2%) and 23 (13.3%) had body mass index (BMI) <30 kg/m2, ≥30 kg/m2 (obese) and ≥40 kg/m2 (morbidly obese) respectively. Compared to non-obese patients, obese patients were younger (mean age 43.4 vs. 48.4 years, p = 0.035) and more likely to develop pneumonitis (61% vs. 44%, p = 0.029). Extracorporeal membrane oxygenation use was greater in morbidly obese compared to non-obese patients (17.4% vs. 4.7%, p = 0.04). Higher mortality rates were observed in non-obese compared to obese patients, but not after adjusting for severity of disease. C-reactive protein (CRP) levels and hospital length of stay (LOS) were similar. Amongst ICU survivors, obese patients had longer ICU LOS (median 11.9 vs. 6.8 days, p = 0.017). Similar trends were observed when only patients infected with A(H1N1)pdm09 were examined. Conclusions Among patients admitted to ICU during the first wave of A(H1N1)pdm09, obese and morbidly obese patients with severe infection were more likely to develop pneumonitis compared to non-obese patients, but mortality rates were not increased. CRP is not an accurate marker of pneumonitis. PMID:23418448

  10. Antiviral susceptibility of influenza viruses isolated from patients pre- and post-administration of favipiravir.

    PubMed

    Takashita, Emi; Ejima, Miho; Ogawa, Rie; Fujisaki, Seiichiro; Neumann, Gabriele; Furuta, Yousuke; Kawaoka, Yoshihiro; Tashiro, Masato; Odagiri, Takato

    2016-08-01

    Favipiravir, a viral RNA-dependent RNA polymerase inhibitor, has recently been approved in Japan for influenza pandemic preparedness. Here, we conducted a cell-based screening system to evaluate the susceptibility of influenza viruses to favipiravir. In this assay, the antiviral activity of favipiravir is determined by inhibition of virus-induced cytopathic effect, which can be measured by using a colorimetric cell proliferation assay. To demonstrate the robustness of the assay, we compared the favipiravir susceptibilities of neuraminidase (NA) inhibitor-resistant influenza A(H1N1)pdm09, A(H3N2), A(H7N9) and B viruses and their sensitive counterparts. No significant differences in the favipiravir susceptibilities were found between NA inhibitor-resistant and sensitive viruses. We, then, examined the antiviral susceptibility of 57 pairs of influenza viruses isolated from patients pre- and post-administration of favipiravir in phase 3 clinical trials. We found that there were no viruses with statistically significant reduced susceptibility to favipiravir or NA inhibitors, although two of 20 paired A(H1N1)pdm09, one of 17 paired A(H3N2) and one of 20 paired B viruses possessed amino acid substitutions in the RNA-dependent RNA polymerase subunits, PB1, PB2 and PA, after favipiravir administration. This is the first report on the antiviral susceptibility of influenza viruses isolated from patients after favipiravir treatment. PMID:27321665

  11. Molecular Epidemiology and Evolution of Influenza Viruses Circulating within European Swine between 2009 and 2013

    PubMed Central

    Watson, Simon J.; Langat, Pinky; Reid, Scott M.; Lam, Tommy Tsan-Yuk; Cotten, Matthew; Kelly, Michael; Van Reeth, Kristien; Qiu, Yu; Simon, Gaëlle; Bonin, Emilie; Foni, Emanuela; Chiapponi, Chiara; Larsen, Lars; Hjulsager, Charlotte; Markowska-Daniel, Iwona; Urbaniak, Kinga; Dürrwald, Ralf; Schlegel, Michael; Huovilainen, Anita; Davidson, Irit; Dán, Ádám; Loeffen, Willie; Edwards, Stephanie; Bublot, Michel; Vila, Thais; Maldonado, Jaime; Valls, Laura; Brown, Ian H.; Pybus, Oliver G.

    2015-01-01

    ABSTRACT The emergence in humans of the A(H1N1)pdm09 influenza virus, a complex reassortant virus of swine origin, highlighted the importance of worldwide influenza virus surveillance in swine. To date, large-scale surveillance studies have been reported for southern China and North America, but such data have not yet been described for Europe. We report the first large-scale genomic characterization of 290 swine influenza viruses collected from 14 European countries between 2009 and 2013. A total of 23 distinct genotypes were identified, with the 7 most common comprising 82% of the incidence. Contrasting epidemiological dynamics were observed for two of these genotypes, H1huN2 and H3N2, with the former showing multiple long-lived geographically isolated lineages, while the latter had short-lived geographically diffuse lineages. At least 32 human-swine transmission events have resulted in A(H1N1)pdm09 becoming established at a mean frequency of 8% across European countries. Notably, swine in the United Kingdom have largely had a replacement of the endemic Eurasian avian virus-like (“avian-like”) genotypes with A(H1N1)pdm09-derived genotypes. The high number of reassortant genotypes observed in European swine, combined with the identification of a genotype similar to the A(H3N2)v genotype in North America, underlines the importance of continued swine surveillance in Europe for the purposes of maintaining public health. This report further reveals that the emergences and drivers of virus evolution in swine differ at the global level. IMPORTANCE The influenza A(H1N1)pdm09 virus contains a reassortant genome with segments derived from separate virus lineages that evolved in different regions of the world. In particular, its neuraminidase and matrix segments were derived from the Eurasian avian virus-like (“avian-like”) lineage that emerged in European swine in the 1970s. However, while large-scale genomic characterization of swine has been reported for southern

  12. Antigenic Drift of A/H3N2/Virus and Circulation of Influenza-Like Viruses During the 2014/2015 Influenza Season in Poland.

    PubMed

    Bednarska, K; Hallmann-Szelińska, E; Kondratiuk, K; Brydak, L B

    2016-01-01

    Morbidity rates of influenza could be greatly reduced due to vaccination. However, the virus is able to evolve through genetic mutations, which is why vaccines with updated composition are necessary every season. Their effectiveness depends on whether there is a good antigenic match between circulating viruses and vaccine strains. In Poland, the 2014/2015 influenza epidemic started in week 5 (January/February) of 2015 and continued until week 17 (April) of 2015. The influenza activity was moderate with the highest incidence of influence-like illness at week 10/2015 (March). During that season, antigenic drift of influenza virus A/H3N2/ occurred causing higher rates of A/H3N2/ infections. Among the 2416 tested specimens, 22.6 % of influenza cases were positive for A/H3N2/, while A/H1N1/pdm09 constituted 14.6 % cases. Influenza A viruses were detected in co-circulation with influenza B viruses; the latter amounted to 34.1 % of all influenza detections. Other detected causes of influenza-like illness consisted of respiratory syncytial virus (RSV), being predominant, and, sporadically, human coronavirus, parainfluenza 1-3, rhinovirus, and adenovirus. Despite low vaccine effectiveness of solely one component, A/H3N2/, the vaccine could mitigate or shorten the length of influenza infection and reduce the number of severe outcomes and mortality. Thus, vaccination against influenza remains the most effective way to prevent illness and possibly fatal outcomes. PMID:26956457

  13. Global update on the susceptibility of human influenza viruses to neuraminidase inhibitors, 2012-2013.

    PubMed

    Meijer, Adam; Rebelo-de-Andrade, Helena; Correia, Vanessa; Besselaar, Terry; Drager-Dayal, Renu; Fry, Alicia; Gregory, Vicky; Gubareva, Larisa; Kageyama, Tsutomu; Lackenby, Angie; Lo, Janice; Odagiri, Takato; Pereyaslov, Dmitriy; Siqueira, Marilda M; Takashita, Emi; Tashiro, Masato; Wang, Dayan; Wong, Sun; Zhang, Wenqing; Daniels, Rod S; Hurt, Aeron C

    2014-10-01

    Emergence of influenza viruses with reduced susceptibility to neuraminidase inhibitors (NAIs) is sporadic, often follows exposure to NAIs, but occasionally occurs in the absence of NAI pressure. The emergence and global spread in 2007/2008 of A(H1N1) influenza viruses showing clinical resistance to oseltamivir due to neuraminidase (NA) H275Y substitution, in the absence of drug pressure, warrants continued vigilance and monitoring for similar viruses. Four World Health Organization (WHO) Collaborating Centres for Reference and Research on Influenza and one WHO Collaborating Centre for the Surveillance, Epidemiology and Control of Influenza (WHO CCs) tested 11,387 viruses collected by WHO-recognized National Influenza Centres (NIC) between May 2012 and May 2013 to determine 50% inhibitory concentration (IC50) data for oseltamivir, zanamivir, peramivir and laninamivir. The data were evaluated using normalized IC50 fold-changes rather than raw IC50 data. Nearly 90% of the 11,387 viruses were from three WHO regions: Western Pacific, the Americas and Europe. Only 0.2% (n=27) showed highly reduced inhibition (HRI) against at least one of the four NAIs, usually oseltamivir, while 0.3% (n=39) showed reduced inhibition (RI). NA sequence data, available from the WHO CCs and from sequence databases (n=3661), were screened for amino acid substitutions associated with reduced NAI susceptibility. Those showing HRI were A(H1N1)pdm09 with NA H275Y (n=18), A(H3N2) with NA E119V (n=3) or NA R292K (n=1) and B/Victoria-lineage with NA H273Y (n=2); amino acid position numbering is A subtype and B type specific. Overall, approximately 99% of circulating viruses tested during the 2012-2013 period were sensitive to all four NAIs. Consequently, these drugs remain an appropriate choice for the treatment and prophylaxis of influenza virus infections. PMID:25043638

  14. Mycophenolic acid, an immunomodulator, has potent and broad-spectrum in vitro antiviral activity against pandemic, seasonal and avian influenza viruses affecting humans.

    PubMed

    To, Kelvin K W; Mok, Ka-Yi; Chan, Andy S F; Cheung, Nam N; Wang, Pui; Lui, Yin-Ming; Chan, Jasper F W; Chen, Honglin; Chan, Kwok-Hung; Kao, Richard Y T; Yuen, Kwok-Yung

    2016-08-01

    Immunomodulators have been shown to improve the outcome of severe pneumonia. We have previously shown that mycophenolic acid (MPA), an immunomodulator, has antiviral activity against influenza A/WSN/1933(H1N1) using a high-throughput chemical screening assay. This study further investigated the antiviral activity and mechanism of action of MPA against contemporary clinical isolates of influenza A and B viruses. The 50 % cellular cytotoxicity (CC50) of MPA in Madin Darby canine kidney cell line was over 50 µM. MPA prevented influenza virus-induced cell death in the cell-protection assay, with significantly lower IC50 for influenza B virus B/411 than that of influenza A(H1N1)pdm09 virus H1/415 (0.208 vs 1.510 µM, P=0.0001). For H1/415, MPA interfered with the early stage of viral replication before protein synthesis. For B/411, MPA may also act at a later stage since MPA was active against B/411 even when added 12 h post-infection. Virus-yield reduction assay showed that the replication of B/411 was completely inhibited by MPA at concentrations ≥0.78 µM, while there was a dose-dependent reduction of viral titer for H1/415. The antiviral effect of MPA was completely reverted by guanosine supplementation. Plaque reduction assay showed that MPA had antiviral activity against eight different clinical isolates of A(H1N1), A(H3N2), A(H7N9) and influenza B viruses (IC50 <1 µM). In summary, MPA has broad-spectrum antiviral activity against human and avian-origin influenza viruses, in addition to its immunomodulatory activity. Together with a high chemotherapeutic index, the use of MPA as an antiviral agent should be further investigated in vivo. PMID:27259985

  15. A Novel Video Tracking Method to Evaluate the Effect of Influenza Infection and Antiviral Treatment on Ferret Activity

    PubMed Central

    Oh, Ding Yuan; Barr, Ian G.; Hurt, Aeron C.

    2015-01-01

    Ferrets are the preferred animal model to assess influenza virus infection, virulence and transmission as they display similar clinical symptoms and pathogenesis to those of humans. Measures of disease severity in the ferret include weight loss, temperature rise, sneezing, viral shedding and reduced activity. To date, the only available method for activity measurement has been the assignment of an arbitrary score by a ‘blind’ observer based on pre-defined responsiveness scale. This manual scoring method is subjective and can be prone to bias. In this study, we described a novel video-tracking methodology for determining activity changes in a ferret model of influenza infection. This method eliminates the various limitations of manual scoring, which include the need for a sole ‘blind’ observer and the requirement to recognise the ‘normal’ activity of ferrets in order to assign relative activity scores. In ferrets infected with an A(H1N1)pdm09 virus, video-tracking was more sensitive than manual scoring in detecting ferret activity changes. Using this video-tracking method, oseltamivir treatment was found to ameliorate the effect of influenza infection on activity in ferret. Oseltamivir treatment of animals was associated with an improvement in clinical symptoms, including reduced inflammatory responses in the upper respiratory tract, lower body weight loss and a smaller rise in body temperature, despite there being no significant reduction in viral shedding. In summary, this novel video-tracking is an easy-to-use, objective and sensitive methodology for measuring ferret activity. PMID:25738900

  16. Virological surveillance of influenza and other respiratory viruses during six consecutive seasons from 2006 to 2012 in Catalonia, Spain.

    PubMed

    Antón, A; Marcos, M A; Torner, N; Isanta, R; Camps, M; Martínez, A; Domínguez, A; Jané, M; Jiménez de Anta, M T; Pumarola, T

    2016-06-01

    Most attention is given to seasonal influenza and respiratory syncytial virus outbreaks, but the cumulative burden caused by other respiratory viruses (RV) is not widely considered. The aim of the present study is to describe the circulation of RV in the general population during six consecutive seasons from 2006 to 2012 in Catalonia, Spain. Cell culture, immunofluorescence and PCR-based assays were used for the RV laboratory-confirmation and influenza subtyping. Phylogenetic and molecular characterizations of viral haemagglutinin, partial neuraminidase and matrix 2 proteins were performed from a representative sampling of influenza viruses. A total of 6315 nasopharyngeal samples were collected, of which 64% were laboratory-confirmed, mainly as influenza A viruses and rhinoviruses. Results show the significant burden of viral aetiological agents in acute respiratory infection, particularly in the youngest cases. The study of influenza strains reveals their continuous evolution through either progressive mutations or by segment reassortments. Moreover, the predominant influenza B lineage was different from that included in the recommended vaccine in half of the studied seasons, supporting the formulation and use of a quadrivalent influenza vaccine. Regarding neuraminidase inhibitors resistance, with the exception of the 2007/08 H275Y seasonal A(H1N1) strains, no other circulating influenza strains carrying known resistance genetic markers were found. Moreover, all circulating A(H1N1)pdm09 and A(H3N2) strains finally became genetically resistant to adamantanes. A wide knowledge of the seasonality patterns of the RV in the general population is well-appreciated, but it is a challenge due to the unpredictable circulation of RV, highlighting the value of local and global RV surveillance. PMID:26939538

  17. Frequent Isolations of Influenza A Viruses (H1N1)pdm09 with Identical Hemagglutinin Sequences for More Than Three Months in Japan

    PubMed Central

    Yoshida, Yu; Tsuneki, Akeno; Itagaki, Asao; Tsuchie, Hideaki; Okada, Takayoshi; Narai, Sakae; Kasagi, Masaaki; Tanaka, Kiyoshi; Ito, Akiko; Ryoke, Kazuo; Kageyama, Seiji

    2015-01-01

    Background Although it has been suggested that antigenic drift does not occur in a single epidemic season in temperate countries, there is not enough evidence on the circulation period of influenza virus with identical nucleotide sequences. Therefore, strains of influenza virus were isolated sequentially during five consecutive epidemic seasons in Japan and their nucleotide sequences were determined. Methods Nasal swabs or aspirated nasal discharges were collected from influenza A virus antigen-positive individuals living in Tottori Prefecture, Japan for five consecutive winters starting in 2009–2010, and subjected to viral isolation, determination of hemagglutinin nucleotide sequence and phylogenic analyses. The nucleotide sequences were compared with each other and also with those of foreign strains in the International Nucleotide Sequence Database. Results Totally 288 A(H1N1)pdm09 strains were tested and those composed 38 clusters with identical ones displaying 100% nucleotide homology. One strain showed sequential infections more than three months without any detectable mutation, and a maximum interval of two detection timings of strains was 94 days. This implies that influenza viruses mutate rarely in an epidemic season in Japan if they can be hypothesized, mutation frequency of influenza viruses being mostly the same among strains. Among these identical strains, two strains were not only identical to other Japanese isolates, but also to those isolated in Mongolia and Thailand in the same epidemic season. Conclusion These results suggest that genetic drift has occurred infrequently in Japan as shown in some other countries. The drifted strains may have generated somewhere else and entered into Japan. These results support the proposed ‘sink-source’ model of viral ecology in which new lineages are seeded from a persistent influenza reservoir in tropical countries to ‘sink’ populations in temperate regions including Japan. PMID:26740735

  18. Determinants of individuals’ risks to 2009 pandemic influenza virus infection at household level amongst Djibouti city residents - A CoPanFlu cross-sectional study

    PubMed Central

    2014-01-01

    Background Following the 2009 swine flu pandemic, a cohort for pandemic influenza (CoPanFlu) study was established in Djibouti, the Horn of Africa, to investigate its case prevalence and risk predictors’ at household level. Methods From the four city administrative districts, 1,045 subjects from 324 households were included during a face-to-face encounter between 11th November 2010 and 15th February 2011. Socio-demographic details were collected and blood samples were analysed in haemagglutination inhibition (HI) assays. Risk assessments were performed in a generalised estimating equation model. Results In this study, the indicator of positive infection status was set at an HI titre of ≥ 80, which was a relevant surrogate to the seroconversion criterion. All positive cases were considered to be either recent infections or past contact with an antigenically closely related virus in humans older than 65 years. An overall sero-prevalence of 29.1% and a geometrical mean titre (GMT) of 39.5% among the residents was observed. Youths, ≤ 25 years and the elderly, ≥65 years had the highest titres, with values of 35.9% and 29.5%, respectively. Significantly, risk was high amongst youths ≤ 25 years, (OR 1.5-2.2), residents of District 4(OR 2.9), students (OR 1.4) and individuals living near to river banks (OR 2.5). Belonging to a large household (OR 0.6), being employed (OR 0.5) and working in open space-outdoor (OR 0.4) were significantly protective. Only 1.4% of the cohort had vaccination against the pandemic virus and none were immunised against seasonal influenza. Conclusion Despite the limited number of incident cases detected by the surveillance system, A(H1N1)pdm09 virus circulated broadly in Djibouti in 2010 and 2011. Age-group distribution of cases was similar to what has been reported elsewhere, with youths at the greatest risk of infection. Future respiratory infection control should therefore be tailored to reach specific and vulnerable

  19. Global update on the susceptibility of human influenza viruses to neuraminidase inhibitors, 2013-2014.

    PubMed

    Takashita, Emi; Meijer, Adam; Lackenby, Angie; Gubareva, Larisa; Rebelo-de-Andrade, Helena; Besselaar, Terry; Fry, Alicia; Gregory, Vicky; Leang, Sook-Kwan; Huang, Weijuan; Lo, Janice; Pereyaslov, Dmitriy; Siqueira, Marilda M; Wang, Dayan; Mak, Gannon C; Zhang, Wenqing; Daniels, Rod S; Hurt, Aeron C; Tashiro, Masato

    2015-05-01

    Four World Health Organization (WHO) Collaborating Centres for Reference and Research on Influenza and one WHO Collaborating Centre for the Surveillance, Epidemiology and Control of Influenza (WHO CCs) tested 10,641 viruses collected by WHO-recognized National Influenza Centres between May 2013 and May 2014 to determine 50% inhibitory concentration (IC50) data for neuraminidase inhibitors (NAIs) oseltamivir, zanamivir, peramivir and laninamivir. In addition, neuraminidase (NA) sequence data, available from the WHO CCs and from sequence databases (n=3206), were screened for amino acid substitutions associated with reduced NAI susceptibility. Ninety-five per cent of the viruses tested by the WHO CCs were from three WHO regions: Western Pacific, the Americas and Europe. Approximately 2% (n=172) showed highly reduced inhibition (HRI) against at least one of the four NAIs, commonly oseltamivir, while 0.3% (n=32) showed reduced inhibition (RI). Those showing HRI were A(H1N1)pdm09 with NA H275Y (n=169), A(H3N2) with NA E119V (n=1), B/Victoria-lineage with NA E117G (n=1) and B/Yamagata-lineage with NA H273Y (n=1); amino acid position numbering is A subtype and B type specific. Although approximately 98% of circulating viruses tested during the 2013-2014 period were sensitive to all four NAIs, a large community cluster of A(H1N1)pdm09 viruses with the NA H275Y substitution from patients with no previous exposure to antivirals was detected in Hokkaido, Japan. Significant numbers of A(H1N1)pdm09 NA H275Y viruses were also detected in China and the United States: phylogenetic analyses showed that the Chinese viruses were similar to those from Japan, while the United States viruses clustered separately from those of the Hokkaido outbreak, indicative of multiple resistance-emergence events. Consequently, global surveillance of influenza antiviral susceptibility should be continued from a public health perspective. PMID:25721488

  20. [Database linkage for surveillance of the influenza A(H1N1)pdm09 pandemic in Brazil, 2009-2010].

    PubMed

    Rossetto, Erika Valeska; Luna, Expedito José de Albuquerque

    2016-07-21

    Based on database linkage, the objective of this study was to describe the epidemiological profile of notified cases and deaths from the new viral subtype of influenza during the influenza pandemic. Secondary data were used from the SINAN (Information System for Notifiable Diseases) and SIM (Mortality Information System) for the years 2009 and 2010. Linkage identified 5,973 deaths of cases notified as pandemic influenza. Of these, 2,170 (36.33%) had been classified in the SINAN as confirmed pandemic influenza, 215 (3.6%) as due to other infectious agents, and 3,340 (55.92%) as ruled out. After linkage, some cases in the SINAN database that were closed as death from influenza (n = 658) or death from other causes (n = 847) could not be located in the SIM database. Database linkage can improve the surveillance system and monitoring of morbidity and mortality. We recommend strengthening influenza surveillance in Brazil using linkage of Ministry of Health databases. PMID:27462844

  1. Compliance to oseltamivir among two populations in Oxfordshire, United Kingdom affected by influenza A(H1N1)pdm09, November 2009--a waste water epidemiology study.

    PubMed

    Singer, Andrew C; Järhult, Josef D; Grabic, Roman; Khan, Ghazanfar A; Fedorova, Ganna; Fick, Jerker; Lindberg, Richard H; Bowes, Michael J; Olsen, Björn; Söderström, Hanna

    2013-01-01

    Antiviral provision remains the focus of many pandemic preparedness plans, however, there is considerable uncertainty regarding antiviral compliance rates. Here we employ a waste water epidemiology approach to estimate oseltamivir (Tamiflu®) compliance. Oseltamivir carboxylate (oseltamivir's active metabolite) was recovered from two waste water treatment plant (WWTP) catchments within the United Kingdom at the peak of the autumnal wave of the 2009 Influenza A (H1N1)pdm09 pandemic. Predictions of oseltamivir consumption from detected levels were compared with two sources of national government statistics to derive compliance rates. Scenario and sensitivity analysis indicated between 3-4 and 120-154 people were using oseltamivir during the study period in the two WWTP catchments and a compliance rate between 45-60%. With approximately half the collected antivirals going unused, there is a clear need to alter public health messages to improve compliance. We argue that a near real-time understanding of drug compliance at the scale of the waste water treatment plant (hundreds to millions of people) can potentially help public health messages become more timely, targeted, and demographically sensitive, while potentially leading to less mis- and un-used antiviral, less wastage and ultimately a more robust and efficacious pandemic preparedness plan. PMID:23613721

  2. Tracking oseltamivir-resistance in New Zealand influenza viruses during a medicine reclassification in 2007, a resistant-virus importation in 2008 and the 2009 pandemic

    PubMed Central

    Peacey, Matthew; Ralston, Jacqui C.; de Joux, Danielle J; Bocacao, Judy; Nicol, Mackenzie; Ziki, Molly; Gunn, Wendy; Wang, Jing; Huang, Q Sue

    2012-01-01

    Introduction Oseltamivir (Tamiflu®) is an important pharmaceutical intervention against the influenza virus. The importance of surveillance for resistance to oseltamivir has been highlighted by two global events: the emergence of an oseltamivir-resistant seasonal influenza A(H1N1) virus in 2008, and emergence of the influenza A(H1N1)pdm09 virus in 2009. Oseltamivir is a prescription medicine in New Zealand, but more timely access has been provided since 2007 by allowing pharmacies to directly dispense oseltamivir to patients with influenza-like illness. Objective To determine the frequency of oseltamivir-resistance in the context of a medicine reclassification in 2007, the importation of an oseltamivir-resistant seasonal influenza virus in 2008, and the emergence of a pandemic in 2009. Methods A total of 1795 influenza viruses were tested for oseltamivir-resistance using a fluorometric neuraminidase inhibition assay. Viruses were collected as part of a sentinel influenza surveillance programme between the years 2006 and 2010. Results All influenza B, influenza A(H3N2) and influenza A(H1N1)pdm09 viruses tested between 2006 and 2010 were shown to be sensitive to oseltamivir. Seasonal influenza A(H1N1) viruses from 2008 and 2009 were resistant to oseltamivir. Sequencing of the neuraminidase gene showed that the resistant viruses contained an H275Y mutation, and S247N was also identified in the neuraminidase gene of one seasonal influenza A(H1N1) virus that exhibited enhanced resistance. Discussion No evidence was found to suggest that increased access to oseltamivir has promoted resistance. A probable importation event was documented for the global 2008 oseltamivir-resistant seasonal A(H1N1) virus nine months after it was first reported in Europe in January 2008. PMID:23908945

  3. Long-Term Shedding of Influenza Virus, Parainfluenza Virus, Respiratory Syncytial Virus and Nosocomial Epidemiology in Patients with Hematological Disorders

    PubMed Central

    Prifert, Christiane; Wedde, Marianne; Puthenparambil, Joe; Weissbrich, Benedikt; Biere, Barbara; Schweiger, Brunhilde; Egerer, Gerlinde; Schnitzler, Paul

    2016-01-01

    Respiratory viruses are a cause of upper respiratory tract infections (URTI), but can be associated with severe lower respiratory tract infections (LRTI) in immunocompromised patients. The objective of this study was to investigate the genetic variability of influenza virus, parainfluenza virus and respiratory syncytial virus (RSV) and the duration of viral shedding in hematological patients. Nasopharyngeal swabs from hematological patients were screened for influenza, parainfluenza and RSV on admission as well as on development of respiratory symptoms. Consecutive swabs were collected until viral clearance. Out of 672 tested patients, a total of 111 patients (17%) were infected with one of the investigated viral agents: 40 with influenza, 13 with parainfluenza and 64 with RSV; six patients had influenza/RSV or parainfluenza/RSV co-infections. The majority of infected patients (n = 75/111) underwent stem cell transplantation (42 autologous, 48 allogeneic, 15 autologous and allogeneic). LRTI was observed in 48 patients, of whom 15 patients developed severe LRTI, and 13 patients with respiratory tract infection died. Phylogenetic analysis revealed a variety of influenza A(H1N1)pdm09, A(H3N2), influenza B, parainfluenza 3 and RSV A, B viruses. RSV A was detected in 54 patients, RSV B in ten patients. The newly emerging RSV A genotype ON1 predominated in the study cohort and was found in 48 (75%) of 64 RSV-infected patients. Furthermore, two distinct clusters were detected for RSV A genotype ON1, identical RSV G gene sequences in these patients are consistent with nosocomial transmission. Long-term viral shedding for more than 30 days was significantly associated with prior allogeneic transplantation (p = 0.01) and was most pronounced in patients with RSV infection (n = 16) with a median duration of viral shedding for 80 days (range 35–334 days). Long-term shedding of respiratory viruses might be a catalyzer of nosocomial transmission and must be considered for

  4. A new laboratory-based surveillance system (Respiratory DataMart System) for influenza and other respiratory viruses in England: results and experience from 2009 to 2012.

    PubMed

    Zhao, H; Green, H; Lackenby, A; Donati, M; Ellis, J; Thompson, C; Bermingham, A; Field, J; Sebastianpillai, P; Zambon, M; Watson, Jm; Pebody, R

    2014-01-01

    During the 2009 influenza A(H1N1) pandemic, a new laboratory-based virological sentinel surveillance system, the Respiratory DataMart System (RDMS), was established in a network of 14 Health Protection Agency (now Public Health England (PHE)) and National Health Service (NHS) laboratories in England. Laboratory results (both positive and negative) were systematically collected from all routinely tested clinical respiratory samples for a range of respiratory viruses including influenza, respiratory syncytial virus (RSV), rhinovirus, parainfluenza virus, adenovirus and human metapneumovirus (hMPV). The RDMS also monitored the occurrence of antiviral resistance of influenza viruses. Data from the RDMS for the 2009–2012 period showed that the 2009 pandemic influenza virus caused three waves of activity with different intensities during the pandemic and post pandemic periods. Peaks in influenza A(H1N1)pdm09 positivity (defined as number of positive samples per total number of samples tested) were seen in summer and autumn in 2009, with slightly higher peak positivity observed in the first post-pandemic season in 2010/2011. The influenza A(H1N1)pdm09 virus strain almost completely disappeared in the second postpandemic season in 2011/2012. The RDMS findings are consistent with other existing community-based virological and clinical surveillance systems. With a large sample size, this new system provides a robust supplementary mechanism, through the collection of routinely available laboratory data at minimum extra cost, to monitor influenza as well as other respiratory virus activity. A near real-time, daily reporting mechanism in the RDMS was established during the London 2012 Olympic and Paralympic Games. Furthermore, this system can be quickly adapted and used to monitor future influenza pandemics and other major outbreaks of respiratory infectious disease, including novel pathogens. PMID:24480060

  5. Quantifying Protection Against Influenza Virus Infection Measured by Hemagglutination-inhibition Assays in Vaccine Trials

    PubMed Central

    Zhao, Xiahong; Fang, Vicky J.; Ohmit, Suzanne E.; Monto, Arnold S.; Cowling, Benjamin J.

    2016-01-01

    Background: Correlations between hemagglutination-inhibition titers (hereafter “titers”) and protection against infection have been identified in historical studies. However, limited information is available about the dynamics of how titer influences protection. Methods: Titers were measured in randomized, placebo-controlled vaccine trials in Hong Kong among pediatrics during September 2009–December 2010 and the United States among adults during Oct 2007–April 2008. Intermediate unobserved titers were imputed using three interpolation methods. As participants were recruited at different times leading to varying exposure to infection relative to entry, a modified proportional hazards model was developed to account for staggered entry into the studies and to quantify the correlation of titers with protection against influenza infections, adjusting for waning in titers. The model was fitted using Markov chain Monte Carlo and importance sampling. Results: A titer of 1:40 was associated with a reduced infection risk of 40%–70% relative to a titer of 1:10, depending on the circulating strain; the corresponding protection associated with a titer of 1:80 was 54%–84%. Results were robust across interpolation methods. The trivalent-inactivated vaccine reduced cumulative incidence of influenza B and influenza A(H3N2) infections by six percentage points (pp; 95% credible interval = 2 pp, 10 pp) and 1 pp (95% credible interval = 0.3 pp, 2 pp) respectively, but not for influenza A(H1N1)pdm09. The live-attenuated vaccine showed little efficacy against influenza A(H3N2) infections. Conclusions: Titers are correlated with protection against influenza infections. The trivalent inactivated vaccine can reduce the risk of influenza A(H3N2) and influenza B infections in the community. PMID:26427723

  6. Critical care surveillance: insights into the impact of the 2010/11 influenza season relative to the 2009/10 pandemic season in England.

    PubMed

    Green, H K; Ellis, J; Galiano, M; Watson, J M; Pebody, R G

    2013-01-01

    In 2010/11, the influenza season in England was marked by a relative increase in impact on the population compared to that seen during the 2009/10 pandemic, with the same influenza subtype, A(H1N1)pdm09, circulating. The peaks in critical care bed occupancy in both seasons coincided with peaks in influenza A(H1N1)pdm09 activity, but onset of influenza in 2010/11 additionally coincided with notably cold weather, a comparatively smaller peak in influenza B activity and increased reports of bacterial co-infection. A bigger impact on critical care services was seen across all regions in England in 2010/11, with, compared to 2009/10, a notable age shift in critical care admissions from children to young adults. The peak of respiratory syncytial virus (RSV) activity did not coincide with critical care admissions, and regression analysis suggested only a small proportion of critical care bed days might be attributed to the virus in either season. Differences in antiviral policy and improved overall vaccine uptake in 2010/11 with an influenza A(H1N1)pdm09 strain containing vaccine between seasons are unlikely to explain the change in impact observed between the two seasons. The reasons behind the relative high level of severe disease in the 2010/11 winter are likely to have resulted from a combination of factors, including an age shift in infection, accumulation of susceptible individuals through waning immunity, new susceptible individuals from new births and cold weather. The importance of further development of severe influenza disease surveillance schemes for future seasons is reinforced. PMID:23787130

  7. Influenza vaccine effectiveness estimates in Europe in a season with three influenza type/subtypes circulating: the I-MOVE multicentre case-control study, influenza season 2012/13.

    PubMed

    Kissling, E; Valenciano, M; Buchholz, U; Larrauri, A; Cohen, J M; Nunes, B; Rogalska, J; Pitigoi, D; Paradowska-Stankiewicz, I; Reuss, A; Jiménez-Jorge, S; Daviaud, I; Guiomar, R; O'Donnell, J; Necula, G; Głuchowska, M; Moren, A

    2014-01-01

    In the fifth season of Influenza Monitoring Vaccine Effectiveness in Europe (I-MOVE), we undertook a multicentre case-control study (MCCS) in seven European Union (EU) Member States to measure 2012/13 influenza vaccine effectiveness against medically attended influenza-like illness (ILI) laboratory confirmed as influenza. The season was characterised by substantial co-circulation of influenza B, A(H1N1)pdm09 and A(H3N2) viruses. Practitioners systematically selected ILI patients to swab ≤7 days of symptom onset. We compared influenza-positive by type/subtype to influenza-negative patients among those who met the EU ILI case definition. We conducted a complete case analysis using logistic regression with study as fixed effect and calculated adjusted vaccine effectiveness (AVE), controlling for potential confounders (age, sex, symptom onset week and presence of chronic conditions). We calculated AVE by type/subtype. Study sites sent 7,954 ILI/acute respiratory infection records for analysis. After applying exclusion criteria, we included 4,627 ILI patients in the analysis of VE against influenza B (1,937 cases), 3,516 for A(H1N1)pdm09 (1,068 cases) and 3,340 for influenza A(H3N2) (730 cases). AVE was 49.3% (95% confidence interval (CI): 32.4 to 62.0) against influenza B, 50.4% (95% CI: 28.4 to 65.6) against A(H1N1)pdm09 and 42.2% (95% CI: 14.9 to 60.7) against A(H3N2). Our results suggest an overall low to moderate AVE against influenza B, A(H1N1)pdm09 and A(H3N2), between 42 and 50%. In this season with many co-circulating viruses, the high sample size enabled stratified AVE by type/subtype. The low estimates indicate seasonal influenza vaccines should be improved to achieve acceptable protection levels. PMID:24556348

  8. Age-specific epidemic waves of influenza and respiratory syncytial virus in a subtropical city.

    PubMed

    Yang, Lin; Chan, Kwok Hung; Suen, Lorna K P; Chan, King Pan; Wang, Xiling; Cao, Peihua; He, Daihai; Peiris, J S Malik; Wong, Chit Ming

    2015-01-01

    Both influenza and respiratory syncytial virus (RSV) are active throughout the year in subtropical or tropical regions, but few studies have reported on age-specific seasonal patterns of these viruses. We examined the age-specific epidemic curves of laboratory-confirmed cases of influenza A (subtyped into seasonal A(H1N1), A(H3N2), and pandemic virus A(H1N1)pdm09), influenza B and respiratory syncytial virus (RSV), in subtropical city Hong Kong from 2004 to 2013. We found that different types and subtypes of influenza showed similar two-peak patterns across age groups, with one peak in winter and another in spring/summer. Age differences were found in epidemic onset time and duration, but none could reach statistical significance (p > 0.05). Age synchrony was found in epidemic peak time for both cool and warm seasons. RSV showed less clear seasonal patterns and non-synchronized epidemic curves across age. In conclusion, age synchrony was found in influenza seasonal epidemics and the 2009 pandemic, but not in RSV. None of the age groups consistently appear as the driving force for seasonal epidemics of influenza and RSV in Hong Kong. PMID:25981824

  9. Age-specific genetic and antigenic variations of influenza A viruses in Hong Kong, 2013–2014

    PubMed Central

    Cao, Peihua; Wong, Chit-Ming; Chan, Kwok-Hung; Wang, Xiling; Chan, King-Pan; Peiris, Joseph Sriyal Malik; Poon, Leo Lit-Man; Yang, Lin

    2016-01-01

    Age-specific genetic and antigenic variations of influenza viruses have not been documented in tropical and subtropical regions. We implemented a systematic surveillance program in two tertiary hospitals in Hong Kong Island, to collect 112 A(H1N1)pdm09 and 254 A(H3N2) positive specimens from 2013 to 2014. Of these, 56 and 72 were identified as genetic variants of the WHO recommended vaccine composition strains, respectively. A subset of these genetic variants was selected for hemagglutination-inhibition (HI) tests, but none appeared to be antigenic variants of the vaccine composition strains. We also found that genetic and antigenicity variations were similar across sex and age groups of ≤18 yrs, 18 to 65 yrs, and ≥65 yrs. Our findings suggest that none of the age groups led other age groups in genetic evolution of influenza virus A strains. Future studies from different regions and longer study periods are needed to further investigate the age and sex heterogeneity of influenza viruses. PMID:27453320

  10. Age-specific genetic and antigenic variations of influenza A viruses in Hong Kong, 2013-2014.

    PubMed

    Cao, Peihua; Wong, Chit-Ming; Chan, Kwok-Hung; Wang, Xiling; Chan, King-Pan; Peiris, Joseph Sriyal Malik; Poon, Leo Lit-Man; Yang, Lin

    2016-01-01

    Age-specific genetic and antigenic variations of influenza viruses have not been documented in tropical and subtropical regions. We implemented a systematic surveillance program in two tertiary hospitals in Hong Kong Island, to collect 112 A(H1N1)pdm09 and 254 A(H3N2) positive specimens from 2013 to 2014. Of these, 56 and 72 were identified as genetic variants of the WHO recommended vaccine composition strains, respectively. A subset of these genetic variants was selected for hemagglutination-inhibition (HI) tests, but none appeared to be antigenic variants of the vaccine composition strains. We also found that genetic and antigenicity variations were similar across sex and age groups of ≤18 yrs, 18 to 65 yrs, and ≥65 yrs. Our findings suggest that none of the age groups led other age groups in genetic evolution of influenza virus A strains. Future studies from different regions and longer study periods are needed to further investigate the age and sex heterogeneity of influenza viruses. PMID:27453320

  11. Differential Biphasic Transcriptional Host Response Associated with Coevolution of Hemagglutinin Quasispecies of Influenza A Virus.

    PubMed

    Manchanda, Himanshu; Seidel, Nora; Blaess, Markus F; Claus, Ralf A; Linde, Joerg; Slevogt, Hortense; Sauerbrei, Andreas; Guthke, Reinhard; Schmidtke, Michaela

    2016-01-01

    Severe influenza associated with strong symptoms and lung inflammation can be caused by intra-host evolution of quasispecies with aspartic acid or glycine in hemagglutinin position 222 (HA-222D/G; H1 numbering). To gain insights into the dynamics of host response to this coevolution and to identify key mechanisms contributing to copathogenesis, the lung transcriptional response of BALB/c mice infected with an A(H1N1)pdm09 isolate consisting HA-222D/G quasispecies was analyzed from days 1 to 12 post infection (p.i). At day 2 p.i. 968 differentially expressed genes (DEGs) were detected. The DEG number declined to 359 at day 4 and reached 1001 at day 7 p.i. prior to recovery. Interestingly, a biphasic expression profile was shown for the majority of these genes. Cytokine assays confirmed these results on protein level exemplarily for two key inflammatory cytokines, interferon gamma and interleukin 6. Using a reverse engineering strategy, a regulatory network was inferred to hypothetically explain the biphasic pattern for selected DEGs. Known regulatory interactions were extracted by Pathway Studio 9.0 and integrated during network inference. The hypothetic gene regulatory network revealed a positive feedback loop of Ifng, Stat1, and Tlr3 gene signaling that was triggered by the HA-G222 variant and correlated with a clinical symptom score indicating disease severity. PMID:27536272

  12. Differential Biphasic Transcriptional Host Response Associated with Coevolution of Hemagglutinin Quasispecies of Influenza A Virus

    PubMed Central

    Manchanda, Himanshu; Seidel, Nora; Blaess, Markus F.; Claus, Ralf A.; Linde, Joerg; Slevogt, Hortense; Sauerbrei, Andreas; Guthke, Reinhard; Schmidtke, Michaela

    2016-01-01

    Severe influenza associated with strong symptoms and lung inflammation can be caused by intra-host evolution of quasispecies with aspartic acid or glycine in hemagglutinin position 222 (HA-222D/G; H1 numbering). To gain insights into the dynamics of host response to this coevolution and to identify key mechanisms contributing to copathogenesis, the lung transcriptional response of BALB/c mice infected with an A(H1N1)pdm09 isolate consisting HA-222D/G quasispecies was analyzed from days 1 to 12 post infection (p.i). At day 2 p.i. 968 differentially expressed genes (DEGs) were detected. The DEG number declined to 359 at day 4 and reached 1001 at day 7 p.i. prior to recovery. Interestingly, a biphasic expression profile was shown for the majority of these genes. Cytokine assays confirmed these results on protein level exemplarily for two key inflammatory cytokines, interferon gamma and interleukin 6. Using a reverse engineering strategy, a regulatory network was inferred to hypothetically explain the biphasic pattern for selected DEGs. Known regulatory interactions were extracted by Pathway Studio 9.0 and integrated during network inference. The hypothetic gene regulatory network revealed a positive feedback loop of Ifng, Stat1, and Tlr3 gene signaling that was triggered by the HA-G222 variant and correlated with a clinical symptom score indicating disease severity. PMID:27536272

  13. Effectiveness of seasonal influenza vaccine in preventing laboratory-confirmed influenza in primary care in the United Kingdom: 2015/16 mid-season results.

    PubMed

    Pebody, Richard; Warburton, Fiona; Ellis, Joanna; Andrews, Nick; Potts, Alison; Cottrell, Simon; Johnston, Jillian; Reynolds, Arlene; Gunson, Rory; Thompson, Catherine; Galiano, Monica; Robertson, Chris; Mullett, David; Gallagher, Naomh; Sinnathamby, Mary; Yonova, Ivelina; Moore, Catherine; McMenamin, Jim; de Lusignan, Simon; Zambon, Maria

    2016-03-31

    In 2015/16, the influenza season in the United Kingdom was dominated by influenza A(H1N1)pdm09 circulation. Virus characterisation indicated the emergence of genetic clusters, with the majority antigenically similar to the current influenza A(H1N1)pdm09 vaccine strain. Mid-season vaccine effectiveness (VE) estimates show an adjusted VE of 41.5% (95% confidence interval (CI): 3.0-64.7) against influenza-confirmed primary care consultations and of 49.1% (95% CI: 9.3-71.5) against influenza A(H1N1)pdm09. These estimates show levels of protection similar to the 2010/11 season, when this strain was first used in the seasonal vaccine. PMID:27074651

  14. Reverse genetics vaccine seeds for influenza: Proof of concept in the source of PB1 as a determinant factor in virus growth and antigen yield.

    PubMed

    Gíria, Marta; Santos, Luís; Louro, João; Rebelo de Andrade, Helena

    2016-09-01

    Growth deficits of reverse genetics vaccine seeds have compromised effective immunization. The impairment has been attributed to sub-optimal protein interactions. Some level of dependence may exist between PB1 and antigenic glycoproteins, however, further research is necessary to clarify the extent to which it can be used in favor of seed production. Our objective was to establish proof of concept on the phenotypic outcome of PB1 source in the PR8: A(H1N1)pdm09 reassortants. Reassortants were generated with the gene constellation of the classical 6:2 PR8: HA, NApdm09 seed prototype and the 5:3 reassortant PR8: HA, NA, PB1pdm09. Viral growth and antigen yield were evaluated 12-60h post-infection. The 5:3 reassortant presented statistically significant growth and antigen yield improvements when compared to the 6:2. We believe these findings to be of promising value to vaccine research towards an improvement of reverse genetic seeds, an overall more cost-effective vaccine manufacture and timely delivery. PMID:27240145

  15. Influenza vaccine effectiveness in preventing inpatient and outpatient cases in a season dominated by vaccine-matched influenza B virus

    PubMed Central

    Martínez-Baz, Iván; Navascués, Ana; Pozo, Francisco; Chamorro, Judith; Albeniz, Esther; Casado, Itziar; Reina, Gabriel; Cenoz, Manuel García; Ezpeleta, Carmen; Castilla, Jesús

    2015-01-01

    Studies that have evaluated the influenza vaccine effectiveness (VE) to prevent laboratory-confirmed influenza B cases are uncommon, and few have analyzed the effect in preventing hospitalized cases. We have evaluated the influenza VE in preventing outpatient and hospitalized cases with laboratory-confirmed influenza in the 2012–2013 season, which was dominated by a vaccine-matched influenza B virus. In the population covered by the Navarra Health Service, all hospitalized patients with influenza-like illness (ILI) and all ILI patients attended by a sentinel network of general practitioners were swabbed for influenza testing, and all were included in a test-negative case-control analysis. VE was calculated as (1-odds ratio)×100. Among 744 patients tested, 382 (51%) were positive for influenza virus: 70% for influenza B, 24% for A(H1N1)pdm09, and 5% for A(H3N2). The overall estimate of VE in preventing laboratory-confirmed influenza was 63% (95% confidence interval (CI): 34 to 79), 55% (1 to 80) in outpatients and 74% (33 to 90) in hospitalized patients. The VE was 70% (41 to 85) against influenza B and 43% (−45 to 78) against influenza A. The VE against virus B was 87% (52 to 96) in hospitalized patients and 56% in outpatients (−5 to 81). Adjusted comparison of vaccination status between inpatient and outpatient cases with influenza B did not show statistically significant differences (odds ratio: 1.13; p = 0.878). These results suggest a high protective effect of the vaccine in the 2012–2013 season, with no differences found for the effect between outpatient and hospitalized cases. PMID:25996366

  16. Comparison of serum hemagglutinin and neuraminidase inhibition antibodies after 2010-2011 trivalent inactivated influenza vaccination in healthcare personnel.

    PubMed

    Laguio-Vila, Maryrose R; Thompson, Mark G; Reynolds, Sue; Spencer, Sarah M; Gaglani, Manjusha; Naleway, Allison; Ball, Sarah; Bozeman, Sam; Baker, Steven; Martínez-Sobrido, Luis; Levine, Min; Katz, Jackie; Fry, Alicia M; Treanor, John J

    2015-01-01

    Background.  Most inactivated influenza vaccines contain purified and standardized hemagglutinin (HA) and residual neuraminidase (NA) antigens. Vaccine-associated HA antibody responses (hemagglutination inhibition [HAI]) are well described, but less is known about the immune response to the NA. Methods.  Serum of 1349 healthcare personnel (HCP) electing or declining the 2010-2011 trivalent-inactivated influenza vaccine ([IIV3], containing A/California/7/2009 p(H1N1), A/Perth/16/2009 [H3N2], B/Brisbane/60/2008 strains) were tested for NA-inhibiting (NAI) antibody by a modified lectin-based assay using pseudotyped N1 and N2 influenza A viruses with an irrelevant (H5) HA. Neuraminidase-inhibiting and HAI antibody titers were evaluated approximately 30 days after vaccination and end-of-season for those with polymerase chain reaction (PCR)-confirmed influenza infection. Results.  In 916 HCP (68%) receiving IIV3, a 2-fold increase in N1 and N2 NAI antibody occurred in 63.7% and 47.3%, respectively. Smaller responses occurred in HCP age >50 years and those without prior 2009-2010 IIV3 nor monovalent A(H1N1)pdm09 influenza vaccinations. Forty-four PCR-confirmed influenza infections were observed, primarily affecting those with lower pre-exposure HAI and NAI antibodies. Higher pre-NAI titers correlated with shorter duration of illness for A(H1N1)pdm09 virus infections. Conclusions.  Trivalent-inactivated influenza vaccine is modestly immunogenic for N1 and N2 antigens in HCP. Vaccines eliciting robust NA immune responses may improve efficacy and reduce influenza-associated morbidity. PMID:25884004

  17. Detection of oseltamivir-resistant pandemic influenza A(H1N1)pdm2009 in Brazil: can community transmission be ruled out?

    PubMed

    Souza, Thiago Moreno L; Resende, Paola C; Fintelman-Rodrigues, Natalia; Gregianini, Tatiana Schaffer; Ikuta, Nilo; Fernandes, Sandra Bianchini; Cury, Ana Luisa Furtado; Rosa, Maria do Carmo Debur; Siqueira, Marilda M

    2013-01-01

    Although surveillance efforts that monitor the emergence of drug-resistant strains of influenza are critical, systematic analysis is overlooked in most developing countries. We report on the occurrence of strains of pandemic influenza A(H1N1)pdm09 with resistance and decreased susceptibility to oseltamivir (OST) in Brazil in 2009, 2011 and 2012. We found 7 mutant viruses, 2 with the mutation S247N and other 5 with the mutation H275Y. Most of these viruses were from samples concentrated in the southern region of Brazil. Some of these resistant viruses were detected prior to the initiation of OST treatment, suggesting that community transmission of mutant viruses may exist. Moreover, we show that one of these OST-resistant (H275Y) strains of A(H1N1)pdm09 was discovered in the tri-border region between Brazil, Argentina and Paraguay, highlighting that this strain could also be found in other Latin American countries. Our findings reinforce the importance of enhanced antiviral resistance surveillance in Brazil and in other Latin American countries to confirm or rule out the community transmission of OST-resistant strains of A(H1N1)pdm09. PMID:24244615

  18. Entry and exit screening of airline travellers during the A(H1N1) 2009 pandemic: a retrospective evaluation

    PubMed Central

    Eckhardt, Rose; Brownstein, John S; Naqvi, Raza; Hu, Wei; Kossowsky, David; Scales, David; Arino, Julien; MacDonald, Michael; Wang, Jun; Sears, Jennifer; Cetron, Martin S

    2013-01-01

    Abstract Objective To evaluate the screening measures that would have been required to assess all travellers at risk of transporting A(H1N1)pdm09 out of Mexico by air at the start of the 2009 pandemic. Methods Data from flight itineraries for travellers who flew from Mexico were used to estimate the number of international airports where health screening measures would have been needed, and the number of travellers who would have had to be screened, to assess all air travellers who could have transported the H1N1 influenza virus out of Mexico during the initial stages of the 2009 A(H1N1) pandemic. Findings Exit screening at 36 airports in Mexico, or entry screening of travellers arriving on direct flights from Mexico at 82 airports in 26 other countries, would have resulted in the assessment of all air travellers at risk of transporting A(H1N1)pdm09 out of Mexico at the start of the pandemic. Entry screening of 116 travellers arriving from Mexico by direct or connecting flights would have been necessary for every one traveller at risk of transporting A(H1N1)pdm09. Screening at just eight airports would have resulted in the assessment of 90% of all air travellers at risk of transporting A(H1N1)pdm09 out of Mexico in the early stages of the pandemic. Conclusion During the earliest stages of the A(H1N1) pandemic, most public health benefits potentially attainable through the screening of air travellers could have been achieved by screening travellers at only eight airports. PMID:23678200

  19. Analytical Sensitivity Comparison between Singleplex Real-Time PCR and a Multiplex PCR Platform for Detecting Respiratory Viruses.

    PubMed

    Parker, Jayme; Fowler, Nisha; Walmsley, Mary Louise; Schmidt, Terri; Scharrer, Jason; Kowaleski, James; Grimes, Teresa; Hoyos, Shanann; Chen, Jack

    2015-01-01

    Multiplex PCR methods are attractive to clinical laboratories wanting to broaden their detection of respiratory viral pathogens in clinical specimens. However, multiplexed assays must be well optimized to retain or improve upon the analytic sensitivity of their singleplex counterparts. In this experiment, the lower limit of detection (LOD) of singleplex real-time PCR assays targeting respiratory viruses is compared to an equivalent panel on a multiplex PCR platform, the GenMark eSensor RVP. LODs were measured for each singleplex real-time PCR assay and expressed as the lowest copy number detected 95-100% of the time, depending on the assay. The GenMark eSensor RVP LODs were obtained by converting the TCID50/mL concentrations reported in the package insert to copies/μL using qPCR. Analytical sensitivity between the two methods varied from 1.2-1280.8 copies/μL (0.08-3.11 log differences) for all 12 assays compared. Assays targeting influenza A/H3N2, influenza A/H1N1pdm09, influenza B, and human parainfluenza 1 and 2 were most comparable (1.2-8.4 copies/μL, <1 log difference). Largest differences in LOD were demonstrated for assays targeting adenovirus group E, respiratory syncytial virus subtype A, and a generic assay for all influenza A viruses regardless of subtype (319.4-1280.8 copies/μL, 2.50-3.11 log difference). The multiplex PCR platform, the GenMark eSensor RVP, demonstrated improved analytical sensitivity for detecting influenza A/H3 viruses, influenza B virus, human parainfluenza virus 2, and human rhinovirus (1.6-94.8 copies/μL, 0.20-1.98 logs). Broader detection of influenza A/H3 viruses was demonstrated by the GenMark eSensor RVP. The relationship between TCID50/mL concentrations and the corresponding copy number related to various ATCC cultures is also reported. PMID:26569120

  20. Analytical Sensitivity Comparison between Singleplex Real-Time PCR and a Multiplex PCR Platform for Detecting Respiratory Viruses

    PubMed Central

    Parker, Jayme; Fowler, Nisha; Walmsley, Mary Louise; Schmidt, Terri; Scharrer, Jason; Kowaleski, James; Grimes, Teresa; Hoyos, Shanann; Chen, Jack

    2015-01-01

    Multiplex PCR methods are attractive to clinical laboratories wanting to broaden their detection of respiratory viral pathogens in clinical specimens. However, multiplexed assays must be well optimized to retain or improve upon the analytic sensitivity of their singleplex counterparts. In this experiment, the lower limit of detection (LOD) of singleplex real-time PCR assays targeting respiratory viruses is compared to an equivalent panel on a multiplex PCR platform, the GenMark eSensor RVP. LODs were measured for each singleplex real-time PCR assay and expressed as the lowest copy number detected 95–100% of the time, depending on the assay. The GenMark eSensor RVP LODs were obtained by converting the TCID50/mL concentrations reported in the package insert to copies/μL using qPCR. Analytical sensitivity between the two methods varied from 1.2–1280.8 copies/μL (0.08–3.11 log differences) for all 12 assays compared. Assays targeting influenza A/H3N2, influenza A/H1N1pdm09, influenza B, and human parainfluenza 1 and 2 were most comparable (1.2–8.4 copies/μL, <1 log difference). Largest differences in LOD were demonstrated for assays targeting adenovirus group E, respiratory syncytial virus subtype A, and a generic assay for all influenza A viruses regardless of subtype (319.4–1280.8 copies/μL, 2.50–3.11 log difference). The multiplex PCR platform, the GenMark eSensor RVP, demonstrated improved analytical sensitivity for detecting influenza A/H3 viruses, influenza B virus, human parainfluenza virus 2, and human rhinovirus (1.6–94.8 copies/μL, 0.20–1.98 logs). Broader detection of influenza A/H3 viruses was demonstrated by the GenMark eSensor RVP. The relationship between TCID50/mL concentrations and the corresponding copy number related to various ATCC cultures is also reported. PMID:26569120

  1. Development of a candidate influenza vaccine based on virus-like particles displaying influenza M2e peptide into the immunodominant region of hepatitis B core antigen: Broad protective efficacy of particles carrying four copies of M2e.

    PubMed

    Tsybalova, Liudmila M; Stepanova, Liudmila A; Kuprianov, Victor V; Blokhina, Elena A; Potapchuk, Marina V; Korotkov, Alexander V; Gorshkov, Andrey N; Kasyanenko, Marina A; Ravin, Nikolai V; Kiselev, Oleg I

    2015-06-26

    A long-term objective when designing influenza vaccines is to create one with broad cross-reactivity that will provide effective control over influenza, no matter which strain has caused the disease. Here we summarize the results from an investigation into the immunogenic and protective capacities inherent in variations of a recombinant protein, HBc/4M2e. This protein contains four copies of the ectodomain from the influenza virus protein M2 (M2e) fused within the immunodominant loop of the hepatitis B virus core antigen (HBc). Variations of this basic design include preparations containing M2e from the consensus human influenza virus; the M2e from the highly pathogenic avian A/H5N1 virus and a combination of two copies from human and two copies from avian influenza viruses. Intramuscular delivery in mice with preparations containing four identical copies of M2e induced high IgG titers in blood sera and bronchoalveolar lavages. It also provoked the formation of memory T-cells and antibodies were retained in the blood sera for a significant period of time post immunization. Furthermore, these preparations prevented the death of 75-100% of animals, which were challenged with lethal doses of virus. This resulted in a 1.2-3.5 log10 decrease in viral replication within the lungs. Moreover, HBc particles carrying only "human" or "avian" M2e displayed cross-reactivity in relation to human (A/H1N1, A/H2N2 and A/H3N2) or A/H5N1 and A(H1N1)pdm09 viruses, respectively; however, with the particles carrying both "human" and "avian" M2e this effect was much weaker, especially in relation to influenza virus A/H5N1. It is apparent from this work that to quickly produce vaccine for a pandemic it would be necessary to have several variations of a recombinant protein, containing four copies of M2e (each one against a group of likely influenza virus strains) with these relevant constructs housed within a comprehensive collection Escherichia coli-producers and maintained ready for use

  2. Highly Predictive Model for a Protective Immune Response to the A(H1N1)pdm2009 Influenza Strain after Seasonal Vaccination.

    PubMed

    Jürchott, Karsten; Schulz, Axel Ronald; Bozzetti, Cecilia; Pohlmann, Dominika; Stervbo, Ulrik; Warth, Sarah; Mälzer, Julia Nora; Waldner, Julian; Schweiger, Brunhilde; Olek, Sven; Grützkau, Andreas; Babel, Nina; Thiel, Andreas; Neumann, Avidan Uriel

    2016-01-01

    Understanding the immune response after vaccination against new influenza strains is highly important in case of an imminent influenza pandemic and for optimization of seasonal vaccination strategies in high risk population groups, especially the elderly. Models predicting the best sero-conversion response among the three strains in the seasonal vaccine were recently suggested. However, these models use a large number of variables and/or information post- vaccination. Here in an exploratory pilot study, we analyzed the baseline immune status in young (<31 years, N = 17) versus elderly (≥50 years, N = 20) donors sero-negative to the newly emerged A(H1N1)pdm09 influenza virus strain and correlated it with the serological response to that specific strain after seasonal influenza vaccination. Extensive multi-chromatic FACS analysis (36 lymphocyte sub-populations measured) was used to quantitatively assess the cellular immune status before vaccination. We identified CD4+ T cells, and amongst them particularly naive CD4+ T cells, as the best correlates for a successful A(H1N1)pdm09 immune response. Moreover, the number of influenza strains a donor was sero-negative to at baseline (NSSN) in addition to age, as expected, were important predictive factors. Age, NSSN and CD4+ T cell count at baseline together predicted sero-protection (HAI≥40) to A(H1N1)pdm09 with a high accuracy of 89% (p-value = 0.00002). An additional validation study (N = 43 vaccinees sero-negative to A(H1N1)pdm09) has confirmed the predictive value of age, NSSN and baseline CD4+ counts (accuracy = 85%, p-value = 0.0000004). Furthermore, the inclusion of donors at ages 31-50 had shown that the age predictive function is not linear with age but rather a sigmoid with a midpoint at about 50 years. Using these results we suggest a clinically relevant prediction model that gives the probability for non-protection to A(H1N1)pdm09 influenza strain after seasonal multi-valent vaccination as a continuous

  3. Highly Predictive Model for a Protective Immune Response to the A(H1N1)pdm2009 Influenza Strain after Seasonal Vaccination

    PubMed Central

    Bozzetti, Cecilia; Pohlmann, Dominika; Stervbo, Ulrik; Warth, Sarah; Mälzer, Julia Nora; Waldner, Julian; Schweiger, Brunhilde; Olek, Sven; Grützkau, Andreas

    2016-01-01

    Understanding the immune response after vaccination against new influenza strains is highly important in case of an imminent influenza pandemic and for optimization of seasonal vaccination strategies in high risk population groups, especially the elderly. Models predicting the best sero-conversion response among the three strains in the seasonal vaccine were recently suggested. However, these models use a large number of variables and/or information post- vaccination. Here in an exploratory pilot study, we analyzed the baseline immune status in young (<31 years, N = 17) versus elderly (≥50 years, N = 20) donors sero-negative to the newly emerged A(H1N1)pdm09 influenza virus strain and correlated it with the serological response to that specific strain after seasonal influenza vaccination. Extensive multi-chromatic FACS analysis (36 lymphocyte sub-populations measured) was used to quantitatively assess the cellular immune status before vaccination. We identified CD4+ T cells, and amongst them particularly naive CD4+ T cells, as the best correlates for a successful A(H1N1)pdm09 immune response. Moreover, the number of influenza strains a donor was sero-negative to at baseline (NSSN) in addition to age, as expected, were important predictive factors. Age, NSSN and CD4+ T cell count at baseline together predicted sero-protection (HAI≥40) to A(H1N1)pdm09 with a high accuracy of 89% (p-value = 0.00002). An additional validation study (N = 43 vaccinees sero-negative to A(H1N1)pdm09) has confirmed the predictive value of age, NSSN and baseline CD4+ counts (accuracy = 85%, p-value = 0.0000004). Furthermore, the inclusion of donors at ages 31–50 had shown that the age predictive function is not linear with age but rather a sigmoid with a midpoint at about 50 years. Using these results we suggest a clinically relevant prediction model that gives the probability for non-protection to A(H1N1)pdm09 influenza strain after seasonal multi-valent vaccination as a continuous

  4. Natural T Cell–mediated Protection against Seasonal and Pandemic Influenza. Results of the Flu Watch Cohort Study

    PubMed Central

    Wang, Lili; Goonetilleke, Nilu; Fragaszy, Ellen B.; Bermingham, Alison; Copas, Andrew; Dukes, Oliver; Millett, Elizabeth R. C.; Nazareth, Irwin; Nguyen-Van-Tam, Jonathan S.; Watson, John M.; Zambon, Maria; Johnson, Anne M.; McMichael, Andrew J.

    2015-01-01

    Rationale: A high proportion of influenza infections are asymptomatic. Animal and human challenge studies and observational studies suggest T cells protect against disease among those infected, but the impact of T-cell immunity at the population level is unknown. Objectives: To investigate whether naturally preexisting T-cell responses targeting highly conserved internal influenza proteins could provide cross-protective immunity against pandemic and seasonal influenza. Methods: We quantified influenza A(H3N2) virus–specific T cells in a population cohort during seasonal and pandemic periods between 2006 and 2010. Follow-up included paired serology, symptom reporting, and polymerase chain reaction (PCR) investigation of symptomatic cases. Measurements and Main Results: A total of 1,414 unvaccinated individuals had baseline T-cell measurements (1,703 participant observation sets). T-cell responses to A(H3N2) virus nucleoprotein (NP) dominated and strongly cross-reacted with A(H1N1)pdm09 NP (P < 0.001) in participants lacking antibody to A(H1N1)pdm09. Comparison of paired preseason and post-season sera (1,431 sets) showed 205 (14%) had evidence of infection based on fourfold influenza antibody titer rises. The presence of NP-specific T cells before exposure to virus correlated with less symptomatic, PCR-positive influenza A (overall adjusted odds ratio, 0.27; 95% confidence interval, 0.11–0.68; P = 0.005, during pandemic [P = 0.047] and seasonal [P = 0.049] periods). Protection was independent of baseline antibodies. Influenza-specific T-cell responses were detected in 43%, indicating a substantial population impact. Conclusions: Naturally occurring cross-protective T-cell immunity protects against symptomatic PCR-confirmed disease in those with evidence of infection and helps to explain why many infections do not cause symptoms. Vaccines stimulating T cells may provide important cross-protective immunity. PMID:25844934

  5. Porcine CD3+NKp46+ Lymphocytes Have NK-Cell Characteristics and Are Present in Increased Frequencies in the Lungs of Influenza-Infected Animals

    PubMed Central

    Mair, Kerstin H.; Stadler, Maria; Talker, Stephanie C.; Forberg, Hilde; Storset, Anne K.; Müllebner, Andrea; Duvigneau, J. Catharina; Hammer, Sabine E.; Saalmüller, Armin; Gerner, Wilhelm

    2016-01-01

    The CD3−NKp46+ phenotype is frequently used for the identification of natural killer (NK) cells in various mammalian species. Recently, NKp46 expression was analyzed in more detail in swine. It could be shown that besides CD3−NKp46+ lymphocytes, a small but distinct population of CD3+NKp46+ cells exists. In this study, we report low frequencies of CD3+NKp46+ lymphocytes in blood, lymph nodes, and spleen, but increased frequencies in non-lymphatic organs, like liver and lung. Phenotypic analyses showed that the majority of CD3+NKp46+ cells coexpressed the CD8αβ heterodimer, while a minor subset expressed the TCR-γδ, which was associated with a CD8αα+ phenotype. Despite these T-cell associated receptors, the majority of CD3+NKp46+ lymphocytes displayed a NK-related phenotype (CD2+CD5−CD6−CD16+perforin+) and expressed mRNA of NKp30, NKp44, and NKG2D at similar levels as NK cells. Functional tests showed that CD3+NKp46+ lymphocytes produced IFN-γ and proliferated upon cytokine stimulation to a similar extent as NK cells, but did not respond to the T-cell mitogen, ConA. Likewise, CD3+NKp46+ cells killed K562 cells with an efficiency comparable to NK cells. Cross-linking of NKp46 and CD3 led to degranulation of CD3+NKp46+ cells, indicating functional signaling pathways for both receptors. Additionally, influenza A(H1N1)pdm09-infected pigs had reduced frequencies of CD3+NKp46+ lymphocytes in blood, but increased frequencies in the lung in the early phase of infection. Thus, CD3+NKp46+ cells appear to be involved in the early phase of influenza infections. In summary, we describe a lymphocyte population in swine with a mixed phenotype of NK and T cells, with results so far indicating that this cell population functionally resembles NK cells. PMID:27471504

  6. Porcine CD3(+)NKp46(+) Lymphocytes Have NK-Cell Characteristics and Are Present in Increased Frequencies in the Lungs of Influenza-Infected Animals.

    PubMed

    Mair, Kerstin H; Stadler, Maria; Talker, Stephanie C; Forberg, Hilde; Storset, Anne K; Müllebner, Andrea; Duvigneau, J Catharina; Hammer, Sabine E; Saalmüller, Armin; Gerner, Wilhelm

    2016-01-01

    The CD3(-)NKp46(+) phenotype is frequently used for the identification of natural killer (NK) cells in various mammalian species. Recently, NKp46 expression was analyzed in more detail in swine. It could be shown that besides CD3(-)NKp46(+) lymphocytes, a small but distinct population of CD3(+)NKp46(+) cells exists. In this study, we report low frequencies of CD3(+)NKp46(+) lymphocytes in blood, lymph nodes, and spleen, but increased frequencies in non-lymphatic organs, like liver and lung. Phenotypic analyses showed that the majority of CD3(+)NKp46(+) cells coexpressed the CD8αβ heterodimer, while a minor subset expressed the TCR-γδ, which was associated with a CD8αα(+) phenotype. Despite these T-cell associated receptors, the majority of CD3(+)NKp46(+) lymphocytes displayed a NK-related phenotype (CD2(+)CD5(-)CD6(-)CD16(+)perforin(+)) and expressed mRNA of NKp30, NKp44, and NKG2D at similar levels as NK cells. Functional tests showed that CD3(+)NKp46(+) lymphocytes produced IFN-γ and proliferated upon cytokine stimulation to a similar extent as NK cells, but did not respond to the T-cell mitogen, ConA. Likewise, CD3(+)NKp46(+) cells killed K562 cells with an efficiency comparable to NK cells. Cross-linking of NKp46 and CD3 led to degranulation of CD3(+)NKp46(+) cells, indicating functional signaling pathways for both receptors. Additionally, influenza A(H1N1)pdm09-infected pigs had reduced frequencies of CD3(+)NKp46(+) lymphocytes in blood, but increased frequencies in the lung in the early phase of infection. Thus, CD3(+)NKp46(+) cells appear to be involved in the early phase of influenza infections. In summary, we describe a lymphocyte population in swine with a mixed phenotype of NK and T cells, with results so far indicating that this cell population functionally resembles NK cells. PMID:27471504

  7. Effectiveness of influenza vaccination of schoolchildren in the city of São Paulo, Brazil, 2009

    PubMed Central

    Gattás, Vera L; Cardoso, Maria Regina A; Mondini, Gabriela; Machado, Clarisse M; Luna, Expedito J A

    2015-01-01

    Background Children play an important role in maintaining the transmission of influenza. Evidence suggests that vaccination of school-age children can reduce transmission to unvaccinated household contacts. We evaluated the direct and indirect effectiveness of the 2009 inactivated seasonal influenza vaccine in vaccinated schoolchildren and their unvaccinated household contacts. Methods This was a double-blind cluster randomized trial involving 10 schools and 1742 schoolchildren as well as 5406 household contacts. The schools were randomly assigned to receive the influenza vaccine or the control vaccine. After vaccination, the schoolchildren and household contacts were followed for 6 months to identify cases of acute respiratory infection (ARI). Reverse-transcriptase polymerase chain reaction was performed for the diagnosis of influenza. Results A total of 632 ARI cases were detected. Of those, 103 tested positive for influenza virus (influenza virus A[H1N1]pdm09 virus in 55 and seasonal influenza viruses in 48). The effectiveness of the vaccine in protecting against seasonal influenza virus infection was 65·0% for the household contacts (95% CI, 19·6–84·3) and 65·0% for the schoolchildren (95% CI, 20·9–84·5). Conclusion Vaccination of schoolchildren significantly protected them and their household contacts against seasonal influenza. PMID:26018131

  8. Pandemic influenza planning, United States, 1978-2008.

    PubMed

    Iskander, John; Strikas, Raymond A; Gensheimer, Kathleen F; Cox, Nancy J; Redd, Stephen C

    2013-06-01

    During the past century, 4 influenza pandemics occurred. After the emergence of a novel influenza virus of swine origin in 1976, national, state, and local US public health authorities began planning efforts to respond to future pandemics. Several events have since stimulated progress in public health emergency planning: the 1997 avian influenza A(H5N1) outbreak in Hong Kong, China; the 2001 anthrax attacks in the United States; the 2003 outbreak of severe acute respiratory syndrome; and the 2003 reemergence of influenza A(H5N1) virus infection in humans. We outline the evolution of US pandemic planning since the late 1970s, summarize planning accomplishments, and explain their ongoing importance. The public health community's response to the 2009 influenza A(H1N1)pdm09 pandemic demonstrated the value of planning and provided insights into improving future plans and response efforts. Preparedness planning will enhance the collective, multilevel response to future public health crises. PMID:23731839

  9. Virological characterization of influenza H1N1pdm09 in Vietnam, 2010-2013

    PubMed Central

    Nguyen, Hang K L; Nguyen, Phuong T K; Nguyen, Thach C; Hoang, Phuong V M; Le, Thanh T; Vuong, Cuong D; Nguyen, Anh P; Tran, Loan T T; Nguyen, Binh G; Lê, Mai Q

    2015-01-01

    Objectives Influenza A/H1N1pdm09 virus was first detected in Vietnam on May 31, 2009, and continues to circulate in Vietnam as a seasonal influenza virus. This study has monitored genotypic and phenotypic changes in this group of viruses during 2010–2013 period. Design and setting We sequenced hemagglutinin (HA) and neuraminidase (NA) genes from representative influenza A/H1N1pdm09 and compared with vaccine strain A/California/07/09 and other contemporary isolates from neighboring countries. Hemagglutination inhibition (HI) and neuraminidase inhibition (NAI) assays also were performed on these isolates. Sample Representative influenza A/H1N1pdm09 isolates (n = 61) from ILI and SARI surveillances in northern Vietnam between 2010 and 2013. Main outcome measures and results The HA and NA phylogenies revealed six and seven groups, respectively. Five isolates (8·2%) had substitutions G155E and N156K in the HA, which were associated with reduced HI titers by antiserum raised against the vaccine virus A/California/07/2009. One isolate from 2011 and one isolate from 2013 had a predicted H275Y substitution in the neuraminidase molecule, which was associated with reduced susceptibility to oseltamivir in a NAI assay. We also identified a D222N change in the HA of a virus isolated from a fatal case in 2013. Conclusions Significant genotypic and phenotypic changes in A/ H1N1pdm09 influenza viruses were detected by the National Influenza Surveillance System (NISS) in Vietnam between 2010 and 2013 highlighting the value of this system to Vietnam and to the region. Sustained NISS and continued virological monitoring of seasonal influenza viruses are required for vaccine policy development in Vietnam. 3 PMID:25966032

  10. Debate Regarding Oseltamivir Use for Seasonal and Pandemic Influenza

    PubMed Central

    Kelly, Heath

    2016-01-01

    A debate about the market-leading influenza antiviral medication, oseltamivir, which initially focused on treatment for generally mild illness, has been expanded to question the wisdom of stockpiling for use in future influenza pandemics. Although randomized controlled trial evidence confirms that oseltamivir will reduce symptom duration by 17–25 hours among otherwise healthy adolescents and adults with community-managed disease, no randomized controlled trials have examined the effectiveness of oseltamivir against more serious outcomes. Observational studies, although criticized on methodologic grounds, suggest that oseltamivir given early can reduce the risk for death by half among persons hospitalized with confirmed infection caused by influenza A(H1N1)pdm09 and influenza A(H5N1) viruses. However, available randomized controlled trial data may not be able to capture the effect of oseltamivir use among hospitalized patients with severe disease. We assert that data on outpatients with relatively mild disease should not form the basis for policies on the management of more severe disease. PMID:27191818

  11. Debate Regarding Oseltamivir Use for Seasonal and Pandemic Influenza.

    PubMed

    Hurt, Aeron C; Kelly, Heath

    2016-06-01

    A debate about the market-leading influenza antiviral medication, oseltamivir, which initially focused on treatment for generally mild illness, has been expanded to question the wisdom of stockpiling for use in future influenza pandemics. Although randomized controlled trial evidence confirms that oseltamivir will reduce symptom duration by 17-25 hours among otherwise healthy adolescents and adults with community-managed disease, no randomized controlled trials have examined the effectiveness of oseltamivir against more serious outcomes. Observational studies, although criticized on methodologic grounds, suggest that oseltamivir given early can reduce the risk for death by half among persons hospitalized with confirmed infection caused by influenza A(H1N1)pdm09 and influenza A(H5N1) viruses. However, available randomized controlled trial data may not be able to capture the effect of oseltamivir use among hospitalized patients with severe disease. We assert that data on outpatients with relatively mild disease should not form the basis for policies on the management of more severe disease. PMID:27191818

  12. Viruses Infecting Reptiles

    PubMed Central

    Marschang, Rachel E.

    2011-01-01

    A large number of viruses have been described in many different reptiles. These viruses include arboviruses that primarily infect mammals or birds as well as viruses that are specific for reptiles. Interest in arboviruses infecting reptiles has mainly focused on the role reptiles may play in the epidemiology of these viruses, especially over winter. Interest in reptile specific viruses has concentrated on both their importance for reptile medicine as well as virus taxonomy and evolution. The impact of many viral infections on reptile health is not known. Koch’s postulates have only been fulfilled for a limited number of reptilian viruses. As diagnostic testing becomes more sensitive, multiple infections with various viruses and other infectious agents are also being detected. In most cases the interactions between these different agents are not known. This review provides an update on viruses described in reptiles, the animal species in which they have been detected, and what is known about their taxonomic positions. PMID:22163336

  13. Effectiveness of Trivalent Inactivated Influenza Vaccine in Children Estimated by a Test-Negative Case-Control Design Study Based on Influenza Rapid Diagnostic Test Results

    PubMed Central

    Yamaguchi, Yoshio; Tomidokoro, Yuka; Sekiguchi, Shinichiro; Mitamura, Keiko; Fujino, Motoko; Shiro, Hiroyuki; Komiyama, Osamu; Taguchi, Nobuhiko; Nakata, Yuji; Yoshida, Naoko; Narabayashi, Atsushi; Myokai, Michiko; Sato, Masanori; Furuichi, Munehiro; Baba, Hiroaki; Fujita, Hisayo; Sato, Akihiro; Ookawara, Ichiro; Tsunematsu, Kenichiro; Yoshida, Makoto; Kono, Mio; Tanaka, Fumie; Kawakami, Chiharu; Kimiya, Takahisa; Takahashi, Takao; Iwata, Satoshi

    2015-01-01

    We assessed vaccine effectiveness (VE) against medically attended, laboratory-confirmed influenza in children 6 months to 15 years of age in 22 hospitals in Japan during the 2013–14 season. Our study was conducted according to a test-negative case-control design based on influenza rapid diagnostic test (IRDT) results. Outpatients who came to our clinics with a fever of 38°C or over and had undergone an IRDT were enrolled in this study. Patients with positive IRDT results were recorded as cases, and patients with negative results were recorded as controls. Between November 2013 and March 2014, a total of 4727 pediatric patients (6 months to 15 years of age) were enrolled: 876 were positive for influenza A, 66 for A(H1N1)pdm09 and in the other 810 the subtype was unknown; 1405 were positive for influenza B; and 2445 were negative for influenza. Overall VE was 46% (95% confidence interval [CI], 39–52). Adjusted VE against influenza A, influenza A(H1N1)pdm09, and influenza B was 63% (95% CI, 56–69), 77% (95% CI, 59–87), and 26% (95% CI, 14–36), respectively. Influenza vaccine was not effective against either influenza A or influenza B in infants 6 to 11 months of age. Two doses of influenza vaccine provided better protection against influenza A infection than a single dose did. VE against hospitalization influenza A infection was 76%. Influenza vaccine was effective against influenza A, especially against influenza A(H1N1)pdm09, but was much less effective against influenza B. PMID:26317334

  14. [ZIKA--VIRUS INFECTION].

    PubMed

    Velev, V

    2016-01-01

    This review summarizes the knowledge of the scientific community for Zika-virus infection. It became popular because of severe congenital damage causes of CNS in newborns whose mothers are infected during pregnancy, as well as the risk of pandemic distribution. Discusses the peculiarities of the biology and ecology of vectors--blood-sucking mosquitoes Aedes; stages in the spread of infection and practical problems which caused during pregnancy. Attention is paid to the recommendations that allow leading national and international medical organizations to deal with the threat Zika-virus infection. PMID:27509655

  15. Epidemiological aspects of influenza A related to climatic conditions during and after a pandemic period in the city of Salvador, Northeastern Brazil.

    PubMed

    Silva, Rosangela de Castro; Siqueira, Marilda Agudo Mendonça; Netto, Eduardo Martins; Bastos, Jacione Silva; Nascimento-Carvalho, Cristiana Maria; Vilas-Boas, Ana Luisa; Bouzas, Maiara Lana; Motta, Fernando do Couto; Brites, Carlos

    2014-04-01

    During the influenza pandemic of 2009, the A(H1N1)pdm09, A/H3N2 seasonal and influenza B viruses were observed to be co-circulating with other respiratory viruses. To observe the epidemiological pattern of the influenza virus between May 2009-August 2011, 467 nasopharyngeal aspirates were collected from children less than five years of age in the city of Salvador. In addition, data on weather conditions were obtained. Indirect immunofluorescence, real-time transcription reverse polymerase chain reaction (RT-PCR), and sequencing assays were performed for influenza virus detection. Of all 467 samples, 34 (7%) specimens were positive for influenza A and of these, viral characterisation identified Flu A/H3N2 in 25/34 (74%) and A(H1N1)pdm09 in 9/34 (26%). Influenza B accounted for a small proportion (0.8%) and the other respiratory viruses for 27.2% (127/467). No deaths were registered and no pattern of seasonality or expected climatic conditions could be established. These observations are important for predicting the evolution of epidemics and in implementing future anti-pandemic measures. PMID:24714967

  16. Epidemiological aspects of influenza A related to climatic conditions during and after a pandemic period in the city of Salvador, northeastern Brazil

    PubMed Central

    Silva, Rosangela de Castro; Siqueira, Marilda Agudo Mendonça; Netto, Eduardo Martins; Bastos, Jacione Silva; Nascimento-Carvalho, Cristiana Maria; Vilas-Boas, Ana Luisa; Bouzas, Maiara Lana; Motta, Fernando do Couto; Brites, Carlos

    2014-01-01

    During the influenza pandemic of 2009, the A(H1N1)pdm09, A/H3N2 seasonal and influenza B viruses were observed to be co-circulating with other respiratory viruses. To observe the epidemiological pattern of the influenza virus between May 2009-August 2011, 467 nasopharyngeal aspirates were collected from children less than five years of age in the city of Salvador. In addition, data on weather conditions were obtained. Indirect immunofluorescence, real-time transcription reverse polymerase chain reaction (RT-PCR), and sequencing assays were performed for influenza virus detection. Of all 467 samples, 34 (7%) specimens were positive for influenza A and of these, viral characterisation identified Flu A/H3N2 in 25/34 (74%) and A(H1N1)pdm09 in 9/34 (26%). Influenza B accounted for a small proportion (0.8%) and the other respiratory viruses for 27.2% (127/467). No deaths were registered and no pattern of seasonality or expected climatic conditions could be established. These observations are important for predicting the evolution of epidemics and in implementing future anti-pandemic measures. PMID:24714967

  17. Human Influenza Virus Infections.

    PubMed

    Peteranderl, Christin; Herold, Susanne; Schmoldt, Carole

    2016-08-01

    Seasonal and pandemic influenza are the two faces of respiratory infections caused by influenza viruses in humans. As seasonal influenza occurs on an annual basis, the circulating virus strains are closely monitored and a yearly updated vaccination is provided, especially to identified risk populations. Nonetheless, influenza virus infection may result in pneumonia and acute respiratory failure, frequently complicated by bacterial coinfection. Pandemics are, in contrary, unexpected rare events related to the emergence of a reassorted human-pathogenic influenza A virus (IAV) strains that often causes increased morbidity and spreads extremely rapidly in the immunologically naive human population, with huge clinical and economic impact. Accordingly, particular efforts are made to advance our knowledge on the disease biology and pathology and recent studies have brought new insights into IAV adaptation mechanisms to the human host, as well as into the key players in disease pathogenesis on the host side. Current antiviral strategies are only efficient at the early stages of the disease and are challenged by the genomic instability of the virus, highlighting the need for novel antiviral therapies targeting the pulmonary host response to improve viral clearance, reduce the risk of bacterial coinfection, and prevent or attenuate acute lung injury. This review article summarizes our current knowledge on the molecular basis of influenza infection and disease progression, the key players in pathogenesis driving severe disease and progression to lung failure, as well as available and envisioned prevention and treatment strategies against influenza virus infection. PMID:27486731

  18. Schmallenberg virus infection.

    PubMed

    Wernike, K; Elbers, A; Beer, M

    2015-08-01

    Since Schmallenberg virus, an orthobunyavirus of the Simbu serogroup, was identified near the German-Dutch border for the first time in late 2011 it has spread extremely quickly and caused a large epidemic in European livestock. The virus, which is transmitted by Culicoides biting midges, infects domestic and wild ruminants. Adult animals show only mild clinical symptoms or none at all, whereas an infection during a critical period of gestation can lead to abortion, stillbirth or the birth of severely malformed offspring. The impact of the disease is usually greater in sheep than in cattle. Vaccination could be an important aspect of disease control. PMID:26601441

  19. Yellow Fever Virus Infection

    PubMed Central

    David-West, Tam. S.; Smith, J. A.

    1971-01-01

    A sequential and quantitative survey of brain and liver of suckling mice for infective virus and complement-fixing antigen, after infection with yellow fever virus, showed that while there was progressive increase of infective virus content in both organs, only the brain showed a corresponding rise in CF antigen. Histopathological examination revealed that the liver was not significantly involved. The target organ was the brain, where the progressive pathological changes culminated in an acute encephalitis by the 3rd day of experiment. Organ destruction began with the molecular layer of the grey matter. But by the 4th day after infection the entire cerebral cortex was involved. At the initial stages the hippocampus was particularly affected. Tissue damage did not appear to be entirely due to the differential quantitative localization of infective virus. It was hypothesized that the CF antigen acting singly or in conjunction with some hypothetical proteins may be principally involved in the pathological outcome of the disease. ImagesFigs. 7-9Figs. 3-6 PMID:5582071

  20. Feline immunodeficiency virus infection.

    PubMed

    Pedersen, N C; Yamamoto, J K; Ishida, T; Hansen, H

    1989-05-01

    Feline immunodeficiency virus (FIV) (formerly feline T-lymphotropic lentivirus or FTLV) was first isolated from a group of cats in Petaluma, California in 1986. The virus is a typical lentivirus in gross and structural morphology. It replicates preferentially but not exclusively in feline T-lymphoblastoid cells, where it causes a characteristic cytopathic effect. The major structural proteins are 10, 17 (small gag), 28 (major core), 31 (endonuclease?), 41 (transmembrane?), 52 (core precursor polyprotein), 54/62 (reverse transcriptase?), and 110/130 (major envelope) kilodaltons in size. The various proteins are antigenically distinguishable from those of other lentiviruses, although serum from EIAV-infected horses will cross-react with some FIV antigens. Kittens experimentally infected with FIV manifest a transient (several days to 2 weeks) fever and neutropenia beginning 4 to 8 weeks after inoculation. This is associated with a generalized lymphadenopathy that persists for up to 9 months. Most cats recover from this initial phase of the disease and become lifelong carriers of the virus. Complete recovery does not occur to any extent in nature or in the laboratory setting. One experimentally infected cat died from a myeloproliferative disorder several months after infection. The terminal AIDS-like phase of the illness has been seen mainly in naturally infected cats. It appears a year or more following the initial infection in an unknown proportion of infected animals. FIV has been identified in cats from all parts of the world. It is most prevalent in high density populations of free roaming cats (feral and pet), and is very uncommon in closed purebred catteries. Male cats are twice as likely to become infected as females. Older male cats adopted as feral or stray animals are at the highest risk of infection, therefore. The infection rate among freely roaming cats rises throughout life, and reaches levels ranging from less than 1% to 12% or more depending on the

  1. Varicella zoster virus infection.

    PubMed

    Gershon, Anne A; Breuer, Judith; Cohen, Jeffrey I; Cohrs, Randall J; Gershon, Michael D; Gilden, Don; Grose, Charles; Hambleton, Sophie; Kennedy, Peter G E; Oxman, Michael N; Seward, Jane F; Yamanishi, Koichi

    2015-01-01

    Infection with varicella zoster virus (VZV) causes varicella (chickenpox), which can be severe in immunocompromised individuals, infants and adults. Primary infection is followed by latency in ganglionic neurons. During this period, no virus particles are produced and no obvious neuronal damage occurs. Reactivation of the virus leads to virus replication, which causes zoster (shingles) in tissues innervated by the involved neurons, inflammation and cell death - a process that can lead to persistent radicular pain (postherpetic neuralgia). The pathogenesis of postherpetic neuralgia is unknown and it is difficult to treat. Furthermore, other zoster complications can develop, including myelitis, cranial nerve palsies, meningitis, stroke (vasculopathy), retinitis, and gastroenterological infections such as ulcers, pancreatitis and hepatitis. VZV is the only human herpesvirus for which highly effective vaccines are available. After varicella or vaccination, both wild-type and vaccine-type VZV establish latency, and long-term immunity to varicella develops. However, immunity does not protect against reactivation. Thus, two vaccines are used: one to prevent varicella and one to prevent zoster. In this Primer we discuss the pathogenesis, diagnosis, treatment, and prevention of VZV infections, with an emphasis on the molecular events that regulate these diseases. For an illustrated summary of this Primer, visit: http://go.nature.com/14xVI1. PMID:27188665

  2. Interpreting sero-epidemiological studies for influenza in a context of non-bracketing sera

    PubMed Central

    Tsang, Tim K.; Fang, Vicky J.; Perera, Ranawaka A. P. M.; Ip, Dennis K. M.; Leung, Gabriel M.; Malik Peiris, J. S.; Cauchemez, Simon; Cowling, Benjamin J.

    2016-01-01

    Background In influenza epidemiology, analysis of paired sera collected from people before and after influenza seasons has been used for decades to study the cumulative incidence of influenza virus infections in populations. However, interpretation becomes challenging when sera are collected after the start or before the end of an epidemic, and do not neatly bracket the epidemic. Methods Serum samples were collected longitudinally in a community-based study. Most participants provided their first serum after the start of circulation of influenza A(H1N1)pdm09 virus in 2009. We developed a Bayesian hierarchical model to correct for non-bracketing sera and estimate the cumulative incidence of infection from the serological data and surveillance data in Hong Kong. Results We analysed 4843 sera from 2097 unvaccinated participants in the study, collected from April 2009 through December 2010. After accounting for non-bracketing, we estimated that the cumulative incidence of H1N1pdm09 virus infection was 45.1% (95% credible interval, CI: 40.2%, 49.2%), 16.5% (95% CI: 13.0%, 19.7%) and 11.3% (95% CI: 5.9%, 17.5%) for children 0–18y, adults 19–50y and older adults >50y respectively. Including all available data substantially increased precision compared to a simpler analysis based only on sera collected at 6-month intervals in a subset of participants. Conclusions We developed a framework for the analysis of antibody titers that accounted for the timing of sera collection with respect to influenza activity and permitted robust estimation of the cumulative incidence of infection during an epidemic. PMID:26427725

  3. [Zika virus infection during pregnancy].

    PubMed

    Picone, O; Vauloup-Fellous, C; D'Ortenzio, E; Huissoud, C; Carles, G; Benachi, A; Faye, A; Luton, D; Paty, M-C; Ayoubi, J-M; Yazdanpanah, Y; Mandelbrot, L; Matheron, S

    2016-05-01

    A Zika virus epidemic is currently ongoing in the Americas. This virus is linked to congenital infections with potential severe neurodevelopmental dysfunction. However, incidence of fetal infection and whether this virus is responsible of other fetal complications are still unknown. National and international public health authorities recommend caution and several prevention measures. Declaration of Zika virus infection is now mandatory in France. Given the available knowledge on Zika virus, we suggest here a review of the current recommendations for management of pregnancy in case of suspicious or infection by Zika virus in a pregnant woman. PMID:27079865

  4. Hepatitis E Virus Infection

    PubMed Central

    Dalton, Harry R.; Abravanel, Florence; Izopet, Jacques

    2014-01-01

    SUMMARY Hepatitis E virus (HEV) infection is a worldwide disease. An improved understanding of the natural history of HEV infection has been achieved within the last decade. Several reservoirs and transmission modes have been identified. Hepatitis E is an underdiagnosed disease, in part due to the use of serological assays with low sensitivity. However, diagnostic tools, including nucleic acid-based tests, have been improved. The epidemiology and clinical features of hepatitis E differ between developing and developed countries. HEV infection is usually an acute self-limiting disease, but in developed countries it causes chronic infection with rapidly progressive cirrhosis in organ transplant recipients, patients with hematological malignancy requiring chemotherapy, and individuals with HIV. HEV also causes extrahepatic manifestations, including a number of neurological syndromes and renal injury. Acute infection usually requires no treatment, but chronic infection should be treated by reducing immunosuppression in transplant patients and/or the use of antiviral therapy. In this comprehensive review, we summarize the current knowledge about the virus itself, as well as the epidemiology, diagnostics, natural history, and management of HEV infection in developing and developed countries. PMID:24396139

  5. Parainfluenza Virus Infection.

    PubMed

    Branche, Angela R; Falsey, Ann R

    2016-08-01

    Human parainfluenza viruses (HPIVs) are single-stranded, enveloped RNA viruses of the Paramyoviridaie family. There are four serotypes which cause respiratory illnesses in children and adults. HPIVs bind and replicate in the ciliated epithelial cells of the upper and lower respiratory tract and the extent of the infection correlates with the location involved. Seasonal HPIV epidemics result in a significant burden of disease in children and account for 40% of pediatric hospitalizations for lower respiratory tract illnesses (LRTIs) and 75% of croup cases. Parainfluenza viruses are associated with a wide spectrum of illnesses which include otitis media, pharyngitis, conjunctivitis, croup, tracheobronchitis, and pneumonia. Uncommon respiratory manifestations include apnea, bradycardia, parotitis, and respiratory distress syndrome and rarely disseminated infection. Immunity resulting from disease in childhood is incomplete and reinfection with HPIV accounts for 15% of respiratory illnesses in adults. Severe disease and fatal pneumonia may occur in elderly and immunocompromised adults. HPIV pneumonia in recipients of hematopoietic stem cell transplant (HSCT) is associated with 50% acute mortality and 75% mortality at 6 months. Though sensitive molecular diagnostics are available to rapidly diagnose HPIV infection, effective antiviral therapies are not available. Currently, treatment for HPIV infection is supportive with the exception of croup where the use of corticosteroids has been found to be beneficial. Several novel drugs including DAS181 appear promising in efforts to treat severe disease in immunocompromised patients, and vaccines to decrease the burden of disease in young children are in development. PMID:27486735

  6. West Nile Virus Infection.

    PubMed

    Sejvar, James J

    2016-06-01

    Although long recognized as a human pathogen, West Nile virus (WNV) emerged as a significant public health problem following its introduction and spread across North America. Subsequent years have seen a greater understanding of all aspects of this viral infection. The North American epidemic resulted in a further understanding of the virology, pathogenesis, clinical features, and epidemiology of WNV infection. Approximately 80% of human WNV infections are asymptomatic. Most symptomatic people experience an acute systemic febrile illness; less than 1% of infected people develop neuroinvasive disease, which typically manifests as meningitis, encephalitis, or anterior myelitis resulting in acute flaccid paralysis. Older age is associated with more severe illness and higher mortality; other risk factors for poor outcome have been challenging to identify. In addition to natural infection through mosquito bites, transfusion- and organ transplant-associated infections have occurred. Since there is no definitive treatment for WNV infection, protection from mosquito bites and other preventative measures are critical. WNV has reached an endemic pattern in North America, but the future epidemiologic pattern is uncertain. PMID:27337465

  7. Zika virus infections.

    PubMed

    de Laval, F; Leparc-Goffart, I; Meynard, J-B; Daubigny, H; Simon, F; Briolant, S

    2016-05-01

    Since its discovery in 1947 in Uganda, the Zika virus (ZIKV) remained in the shadows emerging in 2007 in Micronesia, where hundreds of dengue-like syndromes were reported. Then, in 2013-2014, it was rife in French Polynesia, where the first neurological effects were observed. More recently, its arrival in Brazil was accompanied by an unusually high number of children with microcephaly born to mothers infected with ZIKV during the first trimester of pregnancy. In 2016, the World Health Organization declared ZIKV infection to be a public health emergency and now talks about a ZIKV pandemic. This review aims to summarize the current knowledge about ZIKV infection, successively addressing its transmission, epidemiology, clinical aspects, diagnosis, treatment, and prevention before discussing some perspectives. PMID:27412976

  8. The Possible Impact of Vaccination for Seasonal Influenza on Emergence of Pandemic Influenza via Reassortment

    PubMed Central

    Zhang, Xu-Sheng; Pebody, Richard; De Angelis, Daniela; White, Peter J.; Charlett, Andre; McCauley, John W.

    2014-01-01

    Background One pathway through which pandemic influenza strains might emerge is reassortment from coinfection of different influenza A viruses. Seasonal influenza vaccines are designed to target the circulating strains, which intuitively decreases the prevalence of coinfection and the chance of pandemic emergence due to reassortment. However, individual-based analyses on 2009 pandemic influenza show that the previous seasonal vaccination may increase the risk of pandemic A(H1N1) pdm09 infection. In view of pandemic influenza preparedness, it is essential to understand the overall effect of seasonal vaccination on pandemic emergence via reassortment. Methods and Findings In a previous study we applied a population dynamics approach to investigate the effect of infection-induced cross-immunity on reducing such a pandemic risk. Here the model was extended by incorporating vaccination for seasonal influenza to assess its potential role on the pandemic emergence via reassortment and its effect in protecting humans if a pandemic does emerge. The vaccination is assumed to protect against the target strains but only partially against other strains. We find that a universal seasonal vaccine that provides full-spectrum cross-immunity substantially reduces the opportunity of pandemic emergence. However, our results show that such effectiveness depends on the strength of infection-induced cross-immunity against any novel reassortant strain. If it is weak, the vaccine that induces cross-immunity strongly against non-target resident strains but weakly against novel reassortant strains, can further depress the pandemic emergence; if it is very strong, the same kind of vaccine increases the probability of pandemic emergence. Conclusions Two types of vaccines are available: inactivated and live attenuated, only live attenuated vaccines can induce heterosubtypic immunity. Current vaccines are effective in controlling circulating strains; they cannot always help restrain pandemic

  9. Review Article: Influenza Transmission on Aircraft

    PubMed Central

    Adlhoch, Cornelia

    2016-01-01

    Background: Air travel is associated with the spread of influenza through infected passengers and potentially through in-flight transmission. Contact tracing after exposure to influenza is not performed systematically. We performed a systematic literature review to evaluate the evidence for influenza transmission aboard aircraft. Methods: Using PubMed and EMBASE databases, we identified and critically appraised identified records to assess the evidence of such transmission to passengers seated in close proximity to the index cases. We also developed a bias assessment tool to evaluate the quality of evidence provided in the retrieved studies. Results: We identified 14 peer-reviewed publications describing contact tracing of passengers after possible exposure to influenza virus aboard an aircraft. Contact tracing during the initial phase of the influenza A(H1N1)pdm09 pandemic was described in 11 publications. The studies describe the follow-up of 2,165 (51%) of 4,252 traceable passengers. Altogether, 163 secondary cases were identified resulting in an overall secondary attack rate among traced passengers of 7.5%. Of these secondary cases, 68 (42%) were seated within two rows of the index case. Conclusion: We found an overall moderate quality of evidence for transmission of influenza virus aboard an aircraft. The major limiting factor was the comparability of the studies. A majority of secondary cases was identified at a greater distance than two rows from the index case. A standardized approach for initiating, conducting, and reporting contact tracing could help to increase the evidence base for better assessing influenza transmission aboard aircraft. PMID:27253070

  10. Zika Virus Infection and Microcephaly.

    PubMed

    Millichap, J Gordon

    2016-01-01

    A Task Force established by the Brazil Ministry of Health investigated the possible association of microcephaly with Zika virus infection during pregnancy and a registry for microcephaly cases among women suspected to have had Zika virus infection during pregnancy. PMID:27004142

  11. Influenza neuraminidase inhibitors: antiviral action and mechanisms of resistance

    PubMed Central

    McKimm‐Breschkin, Jennifer L.

    2012-01-01

    Please cite this paper as: McKimm‐Breschkin (2012) Influenza neuraminidase inhibitors: Antiviral action and mechanisms of resistance. Influenza and Other Respiratory Viruses 7(Suppl. 1), 25–36. There are two major classes of antivirals available for the treatment and prevention of influenza, the M2 inhibitors and the neuraminidase inhibitors (NAIs). The M2 inhibitors are cheap, but they are only effective against influenza A viruses, and resistance arises rapidly. The current influenza A H3N2 and pandemic A(H1N1)pdm09 viruses are already resistant to the M2 inhibitors as are many H5N1 viruses. There are four NAIs licensed in some parts of the world, zanamivir, oseltamivir, peramivir, and a long‐acting NAI, laninamivir. This review focuses on resistance to the NAIs. Because of differences in their chemistry and subtle differences in NA structures, resistance can be both NAI‐ and subtype specific. This results in different drug resistance profiles, for example, the H274Y mutation confers resistance to oseltamivir and peramivir, but not to zanamivir, and only in N1 NAs. Mutations at E119, D198, I222, R292, and N294 can also reduce NAI sensitivity. In the winter of 2007–2008, an oseltamivir‐resistant seasonal influenza A(H1N1) strain with an H274Y mutation emerged in the northern hemisphere and spread rapidly around the world. In contrast to earlier evidence of such resistant viruses being unfit, this mutant virus remained fully transmissible and pathogenic and became the major seasonal A(H1N1) virus globally within a year. This resistant A(H1N1) virus was displaced by the sensitive A(H1N1)pdm09 virus. Approximately 0·5–1·0% of community A(H1N1)pdm09 isolates are currently resistant to oseltamivir. It is now apparent that variation in non‐active site amino acids can affect the fitness of the enzyme and compensate for mutations that confer high‐level oseltamivir resistance resulting in minimal impact on enzyme function. PMID:23279894

  12. Influenza vaccine effectiveness in Italy: Age, subtype-specific and vaccine type estimates 2014/15 season.

    PubMed

    Rizzo, Caterina; Bella, Antonino; Alfonsi, Valeria; Puzelli, Simona; Palmieri, Anna Pina; Chironna, Maria; Pariani, Elena; Piatti, Alessandra; Tiberti, Donatella; Ghisetti, Valeria; Rangoni, Roberto; Colucci, Maria Eugenia; Affanni, Paola; Germinario, Cinzia; Castrucci, Maria Rita

    2016-06-01

    The 2014/15 influenza season in Europe was characterised by the circulation of influenza A(H3N2) viruses with an antigenic and genetic mismatch from the vaccine strain A/Texas/50/2012(H3N2) recommended for the Northern hemisphere for the 2014/15 season. Italy, differently from other EU countries where most of the subtyped influenza A viruses were H3N2, experienced a 2014/15 season characterized by an extended circulation of two influenza viruses: A(H1N1)pdm09 and A(H3N2), that both contributed substantially to morbidity. Within the context of the existing National sentinel influenza surveillance system (InfluNet) a test-negative case-control study was established in order to produce vaccine effectiveness (VE) estimates. The point estimates VE were adjusted by age group (<5; 5-15; 15-64; 65+ years), the presence of at least one chronic condition, target group for vaccination and need help for walking or bathing. In Italy, adjusted estimates of the 2014/15 seasonal influenza VE against medically attended influenza-like illness (ILI) laboratory-confirmed as influenza for all age groups were 6.0% (95%CI: -36.5 to 35.2%), 43.6% (95%CI: -3.7 to 69.3%), -84.5% (95%CI: (-190.4 to -17.2%) and 50.7% (95% CI: -2.5 to 76.3%) against any influenza virus, A(H1N1)pdm09, A(H3N2) and B, respectively. These results suggest evidence of good VE against A(H1N1)pdm09 and B viruses in Italy and evidence of lack of VE against A(H3N2) virus due to antigenic and genetic mismatch between circulating A(H3N2) and the respective 2014/15 vaccine strain. PMID:27154392

  13. Human Immunodeficiency Virus (HIV) Primary Infection

    MedlinePlus

    ... rashes clinical tools newsletter | contact Share | Human Immunodeficiency Virus (HIV) Primary Infection Information for adults A A ... weeks following exposure to HIV (the human immunodeficiency virus). Chronic infection with this virus can cause AIDS ( ...

  14. Respiratory Syncytial Virus Infections

    MedlinePlus

    Respiratory syncytial virus (RSV) causes mild, cold-like symptoms in adults and older healthy children. It can cause serious problems in ... tests can tell if your child has the virus. There is no specific treatment. You should give ...

  15. Human Papilloma Virus Infections

    PubMed Central

    Wright, V. Cecil

    1989-01-01

    Genital warts are believed to be caused by human papilloma viruses and to be sexually transmitted. The viruses are classified by DNA types, which appear to cause different types of disease. The choice of treatment, and usually its success rate, vary according to the type of disease and its location. PMID:21248973

  16. [Influenza surveillance in five consecutive seasons during post pandemic period: results from National Influenza Center, Turkey].

    PubMed

    Altaş, Ayşe Başak; Bayrakdar, Fatma; Korukluoğlu, Gülay

    2016-07-01

    Influenza surveillance provides data about the characteristics of influenza activity, types, sub-types and antigenic properties of the influenza viruses in circulation in a region. Surveillance also provides for the preparation against potential influenza pandemics with the identification of the genetic properties of viruses and the mutant strains that could pose a threat. In this study, data in the scope of national influenza surveillance carried out by National Influenza Center, Turkey for five consecutive influenza seasons between 2010-2015, following the A(H1N1)pdm09 virus pandemic, have been presented and evaluated. A total of 15.149 respiratory samples, including 8.894 sentinel and 6.255 non-sentinel specimens, during 2010-2015 influenza seasons, within the periods between September and May, were evaluated in our center. All samples were tested using real-time reverse transcriptase PCR (rRT-PCR) for the presence of influenza virus types and subtypes. Within the sentinel influenza surveillance, the samples that were detected negative for influenza viruses, have also been tested for the other respiratory viruses (respiratory syncytial virus, rhinoviruses, paramyxoviruses, coronaviruses) using the same technique. Further analysis, including virus isolation by cell culture inoculation and antigenic characterization by hemagglutination inhibiton test were performed for the samples found positive for influenza A and B viruses. Selected representative virus isolates have been sent to WHO reference laboratory for the sequence analysis. In the study, influenza virus positivity rates detected for all of the samples (sentinel+non-sentinel) were as follows; 34% (779/2316) in 2010-11 season; 25% (388/1554) in 2011-12; 20% (696/3541) in 2012-13; 23% (615/2678) in 2013-14; and 26% (1332/5060) in 2014-15. When all the samples were considered for influenza A and B viruses, the positivity rates for the seasons of 2010-11; 2011-12; 2012-13; 2013-14; 2014-15 were determined as

  17. Respiratory Syncytial Virus Infections

    MedlinePlus

    ... countertops. Washing your hands often and not sharing eating and drinking utensils are simple ways to help prevent the spread of RSV infection. There is currently no vaccine for RSV. Centers for Disease Control and Prevention

  18. Hepatitis Virus Infections in Poultry.

    PubMed

    Yugo, Danielle M; Hauck, Ruediger; Shivaprasad, H L; Meng, Xiang-Jin

    2016-09-01

    Viral hepatitis in poultry is a complex disease syndrome caused by several viruses belonging to different families including avian hepatitis E virus (HEV), duck hepatitis B virus (DHBV), duck hepatitis A virus (DHAV-1, -2, -3), duck hepatitis virus Types 2 and 3, fowl adenoviruses (FAdV), and turkey hepatitis virus (THV). While these hepatitis viruses share the same target organ, the liver, they each possess unique clinical and biological features. In this article, we aim to review the common and unique features of major poultry hepatitis viruses in an effort to identify the knowledge gaps and aid the prevention and control of poultry viral hepatitis. Avian HEV is an Orthohepevirus B in the family Hepeviridae that naturally infects chickens and consists of three distinct genotypes worldwide. Avian HEV is associated with hepatitis-splenomegaly syndrome or big liver and spleen disease in chickens, although the majority of the infected birds are subclinical. Avihepadnaviruses in the family of Hepadnaviridae have been isolated from ducks, snow geese, white storks, grey herons, cranes, and parrots. DHBV evolved with the host as a noncytopathic form without clinical signs and rarely progressed to chronicity. The outcome for DHBV infection varies by the host's ability to elicit an immune response and is dose and age dependent in ducks, thus mimicking the pathogenesis of human hepatitis B virus (HBV) infections and providing an excellent animal model for human HBV. DHAV is a picornavirus that causes a highly contagious virus infection in ducks with up to 100% flock mortality in ducklings under 6 wk of age, while older birds remain unaffected. The high morbidity and mortality has an economic impact on intensive duck production farming. Duck hepatitis virus Types 2 and 3 are astroviruses in the family of Astroviridae with similarity phylogenetically to turkey astroviruses, implicating the potential for cross-species infections between strains. Duck astrovirus (DAstV) causes

  19. Probiotics in respiratory virus infections.

    PubMed

    Lehtoranta, L; Pitkäranta, A; Korpela, R

    2014-08-01

    Viral respiratory infections are the most common diseases in humans. A large range of etiologic agents challenge the development of efficient therapies. Research suggests that probiotics are able to decrease the risk or duration of respiratory infection symptoms. However, the antiviral mechanisms of probiotics are unclear. The purpose of this paper is to review the current knowledge on the effects of probiotics on respiratory virus infections and to provide insights on the possible antiviral mechanisms of probiotics. A PubMed and Scopus database search was performed up to January 2014 using appropriate search terms on probiotic and respiratory virus infections in cell models, in animal models, and in humans, and reviewed for their relevance. Altogether, thirty-three clinical trials were reviewed. The studies varied highly in study design, outcome measures, probiotics, dose, and matrices used. Twenty-eight trials reported that probiotics had beneficial effects in the outcome of respiratory tract infections (RTIs) and five showed no clear benefit. Only eight studies reported investigating viral etiology from the respiratory tract, and one of these reported a significant decrease in viral load. Based on experimental studies, probiotics may exert antiviral effects directly in probiotic-virus interaction or via stimulation of the immune system. Although probiotics seem to be beneficial in respiratory illnesses, the role of probiotics on specific viruses has not been investigated sufficiently. Due to the lack of confirmatory studies and varied data available, more randomized, double-blind, and placebo-controlled trials in different age populations investigating probiotic dose response, comparing probiotic strains/genera, and elucidating the antiviral effect mechanisms are necessary. PMID:24638909

  20. Pediatric human immunodeficiency virus infection.

    PubMed Central

    Domachowske, J B

    1996-01-01

    In the past decade, an increase in pediatric human immunodeficiency virus (HIV) infection has had a substantial impact on childhood morbidity and mortality worldwide. The vertical transmission of HIV from mother to infant accounts for the vast majority of these cases. Identification of HIV-infected pregnant women needs to be impoved so that appropriate therapy can be initiated for both mothers and infants. While recent data demonstrate a dramatic decrease in HIV transmission from a subset of women treated with zidovudine during pregnancy, further efforts at reducing transmission are desperately needed. This review focuses on vertically transmitted HIV infection in children, its epidemiology, diagnostic criteria, natural history, and clinical manifestations including infectious and noninfectious complications. An overview of the complex medical management of these children ensues, including the use of antiretroviral therapy. Opportunistic infection prophylaxis is reviewed, along with the important role of other supportive therapies. PMID:8894346

  1. Moderate influenza vaccine effectiveness against hospitalisation with A(H3N2) and A(H1N1) influenza in 2013-14: Results from the InNHOVE network.

    PubMed

    Rondy, M; Castilla, J; Launay, O; Costanzo, S; Ezpeleta, C; Galtier, F; de Gaetano Donati, K; Moren, A

    2016-05-01

    We conducted a multicentre test negative case control study to estimate the 2013-14 influenza vaccine effectiveness (IVE) against hospitalised laboratory confirmed influenza in 12 hospitals in France, Italy and Spain. We included all ≥18 years hospitalised patients targeted by local influenza vaccination campaign reporting an influenza-like illness within 7 days before admission. We defined as cases patients RT-PCR positive for influenza and as controls those negative for all influenza virus. We used a logistic regression to calculate IVE adjusted for country, month of onset, chronic diseases and age. We included 104 A(H1N1)pdm09, 157 A(H3N2) cases and 585 controls. The adjusted IVE was 42.8% (95%CI: 6.3;65;0) against A(H1N1)pdm09. It was respectively 61.4% (95%CI: -1.9;85.4), 39.4% (95%CI: -32.2;72.2) and 19.7% (95%CI:-148.1;74.0) among patients aged 18-64, 65-79 and ≥80 years. The adjusted IVE against A(H3N2) was 38.1% (95%CI: 8.3;58.2) overall. It was respectively 7.8% (95%CI: -145.3;65.4), 25.6% (95%CI: -36.0;59.2) and 55.2% (95%CI: 15.4;76.3) among patients aged 18-64, 65-79 and ≥80 years. These results suggest a moderate and age varying effectiveness of the 2013-14 influenza vaccine to prevent hospitalised laboratory-confirmed influenza. While vaccination remains the most effective prevention measure, developing more immunogenic influenza vaccines is needed to prevent severe outcomes among target groups. PMID:27065000

  2. Immunosuppression During Influenza Virus Infection

    PubMed Central

    Kantzler, G. B.; Lauteria, S. F.; Cusumano, C. L.; Lee, J. D.; Ganguly, R.; Waldman, R. H.

    1974-01-01

    The effects of a live attenuated influenza vaccine and subsequent challenge with virulent influenza virus on the delayed hypersensitivity skin test, and the in vitro response of lymphocytes were evaluated. Volunteers were skin tested before and after administration of vaccine or placebo and challenge with PPD (a purified protein derivative of Mycobacterium tuberculosis), candida, mumps, and trichophytin, and their lymphocytes were tested for [3H]thymidine uptake in response to phytohemagglutin. Of eight volunteers who showed evidence of viral replication after administration of the attenuated vaccine, four had a significant diminution in their skin test response, whereas 8 of 13 volunteers infected with virulent influenza virus showed a diminution. Of the 21 volunteers who were infected with either attenuated or virulent influenza virus, 12 showed suppression of their phytohemagglutin response. None of the volunteers who were given placebo vaccine, or who showed no evidence for viral replication after immunization or challenge, had a suppression of their skin test or phytohemagglutin responses. Although most of the infected volunteers demonstrated suppression of their T-cell function, there was no evidence of a similar suppression of B-cell function. PMID:16558116

  3. Age and Sex Differences in Rates of Influenza-Associated Hospitalizations in Hong Kong.

    PubMed

    Wang, Xi-Ling; Yang, Lin; Chan, Kwok-Hung; Chan, King-Pan; Cao, Pei-Hua; Lau, Eric Ho-Yin; Peiris, J S Malik; Wong, Chit-Ming

    2015-08-15

    Few studies have explored age and sex differences in the disease burden of influenza, although men and women probably differ in their susceptibility to influenza infections. In this study, quasi-Poisson regression models were applied to weekly age- and sex-specific hospitalization numbers of pneumonia and influenza cases in the Hong Kong SAR, People's Republic of China, from 2004 to 2010. Age and sex differences were assessed by age- and sex-specific rates of excess hospitalization for influenza A subtypes A(H1N1), A(H3N2), and A(H1N1)pdm09 and influenza B, respectively. We found that, in children younger than 18 years, boys had a higher excess hospitalization rate than girls, with the male-to-female ratio of excess rate (MFR) ranging from 1.1 to 2.4. MFRs of hospitalization associated with different types/subtypes were less than 1.0 for adults younger than 40 years except for A(H3N2) (MFR = 1.6), while all the MFRs were equal to or higher than 1.0 in adults aged 40 years or more except for A(H1N1)pdm09 in elderly persons aged 65 years or more (MFR = 0.9). No MFR was found to be statistically significant (P < 0.05) for hospitalizations associated with influenza type/subtype. There is some limited evidence on age and sex differences in hospitalization associated with influenza in the subtropical city of Hong Kong. PMID:26219977

  4. Avian Influenza A Virus Infections in Humans

    MedlinePlus

    ... Research Making a Candidate Vaccine Virus Related Links Influenza Types Seasonal Avian Swine Variant Pandemic Other Get ... Submit What's this? Submit Button Past Newsletters Avian Influenza A Virus Infections in Humans Language: English Españ ...

  5. Uveitis Associated with Zika Virus Infection.

    PubMed

    Furtado, João M; Espósito, Danillo L; Klein, Taline M; Teixeira-Pinto, Tomás; da Fonseca, Benedito A

    2016-07-28

    An adult patient recovered from acute Zika virus infection, but ocular symptoms subsequently developed. Anterior uveitis was diagnosed, and Zika virus was identified in the aqueous humor. PMID:27332784

  6. Neuropathology of Zika Virus Infection

    PubMed Central

    Solomon, Isaac H; Milner, Danny A; Folkerth, Rebecca D

    2016-01-01

    Zika virus (ZIKV) is a member of the Flaviviridae family that had been associated only with mild disease prior to the 2015 outbreak in Brazil. A dramatic increase in reported cases of microcephaly and Guillain-Barré syndrome during this time prompted significant research into possible associations with ZIKV and its neurotropic properties. Infection of neural progenitor cells and organoids have been shown to induce apoptosis and dysregulation of growth, and mouse studies have demonstrated viral replication in brain tissue in adults, as well as vertical transmission resulting in embryonic brain abnormalities. Large case series of clinical and radiological findings of congenital ZIKV infection have begun to be published; however, pathology reports have been limited to two case reports and two small case series. Thus far, the findings have largely been restricted to the brain and include diffuse grey and white matter involvement consisting of dystrophic calcifications, gliosis, microglial nodules, neuronophagia, and scattered lymphocytes. Mild chronic villitis was observed in the placental tissue in some cases, and the remaining organs were essentially uninvolved. Larger, systematic studies, including correlation of histological findings with gestational age at the time of maternal infection, will be required to determine the full range of Zika virus-induced abnormalities and to help guide future clinical decision making. PMID:27525286

  7. CELLULAR PATHOLOGY OF A GRANULOSIS VIRUS INFECTION

    EPA Science Inventory

    Nuclear and cytoplasmic ultrastructural changes were examined in Spodoptera frugiperda (SF) larval fat body cells infected with granulosis virus (GV). Soon after infection necleocapsidlike structures were observed within the nucleus associated with nuclear pores. The earliest cel...

  8. Zika Virus Infection and Zika Fever: Frequently Asked Questions

    MedlinePlus

    ... Updated: 25 March 2016 ABOUT ZIKA What is Zika virus infection? Zika virus infection is caused by the ... possible to characterize the disease better. How is Zika virus transmitted? Zika virus is transmitted to people through ...

  9. Current Management of Hepatitis C Virus Infection.

    PubMed

    Mah'moud, Mitchell A

    2016-01-01

    At least 3 million people in the United States are infected with hepatitis C virus (HCV) infection. Unfortunately, 75% of infected individuals remain undiagnosed and untreated, putting them at risk of advanced liver disease. Because the majority of infected individuals are baby boomers, many societies and organizations recommend HCV screening of persons born between 1945 and 1965. PMID:27154887

  10. Modeling Zika Virus Infection in Mice.

    PubMed

    Rossi, Shannan L; Vasilakis, Nikos

    2016-07-01

    Understanding the link between Zika virus (ZIKV) infection and microcephaly requires in vivo models of ZIKV infection in pregnant adults and fetuses. Three studies recently generated such mouse models of ZIKV infection, which corroborate previous in vitro evidence linking ZIKV infection and apoptosis induction in neurons and progenitors to microcephaly. PMID:27392219

  11. The greasy response to virus infections

    PubMed Central

    Tanner, Lukas Bahati; Lee, Benhur

    2013-01-01

    Previews Virus replication requires lipid metabolism, but how lipids mediate virus infection remains obscure. In this issue, Amini-Bavil-Olyaee et al. (2013) reveal that IFITM proteins disturb cholesterol homeostasis to block virus entry. Previously in Cell, Morita and colleagues (2013) showed the antiviral potency of the lipid mediator protectin D1. PMID:23601099

  12. Systems analysis of West Nile virus infection.

    PubMed

    Suthar, Mehul S; Pulendran, Bali

    2014-06-01

    Emerging and re-emerging mosquito-borne viruses continue to pose a significant threat to human health throughout the world. Over the past decade, West Nile virus (WNV), Dengue virus (DENV), and Chikungunya virus (CHIKV), have caused annual epidemics of virus-induced encephalitis, hemorrhagic fever\\shock syndromes, and arthritis, respectively. Currently, no specific antiviral therapies or vaccines exist for use in humans to combat or prevent these viral infections. Thus, there is a pressing need to define the virus-host interactions that govern immunity and infection outcome. Recent technological breakthroughs in 'omics' resources and high-throughput based assays are beginning to accelerate antiviral drug discovery and improve on current strategies for vaccine design. In this review, we highlight studies with WNV and discuss how traditional and systems biological approaches are being used to rapidly identify novel host targets for therapeutic intervention and develop a deeper conceptual understanding of the host response to virus infection. PMID:24851811

  13. Effect of double dose oseltamivir on clinical and virological outcomes in children and adults admitted to hospital with severe influenza: double blind randomised controlled trial

    PubMed Central

    2013-01-01

    Objective To investigate the validity of recommendations in treatment guidelines to use higher than approved doses of oseltamivir in patients with severe influenza. Design Double blind randomised trial. Setting Thirteen hospitals in Indonesia, Singapore, Thailand, and Vietnam. Participants Patients aged ≥1 year admitted to hospital with confirmed severe influenza. Interventions Oral oseltamivir at double dose (150 mg twice a day/paediatric equivalent) versus standard dose (75 mg twice a day/paediatric equivalent). Main outcome measure Viral status according to reverse transcriptase polymerase chain reaction (RT-PCR) for influenza RNA in nasal and throat swabs on day five. Results Of 326 patients (including 246 (75.5%) children aged <15), 165 and 161 were randomised to double or standard dose oseltamivir, respectively. Of these, 260 (79.8%) were infected with influenza virus A (133 (40.8%) with A/H3N2, 72 (22.1%) with A/H1N1-pdm09, 38 (11.7%) with seasonal A/H1N1, 17 (5.2%) with A/H5N1) and 53 (16.2%) with influenza virus B. A further 3.9% (13) were false positive by rapid antigen test (negative by RT-PCR and no rise in convalescent haemagglutination inhibition titers). Similar proportions of patients were negative for RT-PCR on day five of treatment: 115/159 (72.3%, 95% confidence interval 64.9% to 78.7%) double dose recipients versus 105/154 (68.2%, 60.5% to 75.0%) standard dose recipients; difference 4.2% (−5.9 to 14.2); P=0.42. No differences were found in clearance of virus in subgroup analyses by virus type/subtype, age, and duration of illness before randomisation. Mortality was similar: 12/165 (7.3%, 4.2% to 12.3%) in double dose recipients versus 9/161 (5.6%, 3.0% to 10.3%) in standard dose recipients. No differences were found between double and standard dose arms in median days on supplemental oxygen (3 (interquartile range 2-5) v 3.5 (2-7)), in intensive care (4.5 (3-6) v 5 (2-11), and on mechanical ventilation (2.5 (1-16) v 8 (1-16)), respectively

  14. RNA Viruses Infecting Pest Insects

    Technology Transfer Automated Retrieval System (TEKTRAN)

    RNA viruses are viruses whose genetic material is ribonucleic acid (RNA). RNA viruses may be double or single-stranded based on the type of RNA they contain. Single-stranded RNA viruses can be further grouped into negative sense or positive-sense viruses according to the polarity of their RNA. Fur...

  15. Hendra Virus Infection in Dog, Australia, 2013

    PubMed Central

    Gabor, Melinda; Poe, Ian; Neale, Kristie; Chaffey, Kim; Finlaison, Deborah S.; Gu, Xingnian; Hick, Paul M.; Read, Andrew J.; Wright, Therese; Middleton, Deborah

    2015-01-01

    Hendra virus occasionally causes severe disease in horses and humans. In Australia in 2013, infection was detected in a dog that had been in contact with an infected horse. Abnormalities and viral RNA were found in the dog’s kidney, brain, lymph nodes, spleen, and liver. Dogs should be kept away from infected horses. PMID:26583697

  16. The Epidemiology of Human Immunodeficiency Virus Infection.

    ERIC Educational Resources Information Center

    Glasner, Peter D.; Kaslow, Richard A.

    1990-01-01

    Reviews epidemiology and natural history of human immunodeficiency virus-Type 1 (HIV-1) infection. Discusses early and late clinical manifestations, diagnosis of infection, incubation and latency periods, and survival time. Reviews data from published literature on distribution of HIV infection in adult United States population and factors that…

  17. Hendra Virus Infection in Dog, Australia, 2013.

    PubMed

    Kirkland, Peter D; Gabor, Melinda; Poe, Ian; Neale, Kristie; Chaffey, Kim; Finlaison, Deborah S; Gu, Xingnian; Hick, Paul M; Read, Andrew J; Wright, Therese; Middleton, Deborah

    2015-12-01

    Hendra virus occasionally causes severe disease in horses and humans. In Australia in 2013, infection was detected in a dog that had been in contact with an infected horse. Abnormalities and viral RNA were found in the dog's kidney, brain, lymph nodes, spleen, and liver. Dogs should be kept away from infected horses. PMID:26583697

  18. Influenza Virus Infection of Marine Mammals.

    PubMed

    Fereidouni, Sasan; Munoz, Olga; Von Dobschuetz, Sophie; De Nardi, Marco

    2016-03-01

    Interspecies transmission may play a key role in the evolution and ecology of influenza A viruses. The importance of marine mammals as hosts or carriers of potential zoonotic pathogens such as highly pathogenic H5 and H7 influenza viruses is not well understood. The fact that influenza viruses are some of the few zoonotic pathogens known to have caused infection in marine mammals, evidence for direct transmission of influenza A virus H7N7 subtype from seals to man, transmission of pandemic H1N1 influenza viruses to seals and also limited evidence for long-term persistence of influenza B viruses in seal populations without significant genetic change, makes monitoring of influenza viruses in marine mammal populations worth being performed. In addition, such monitoring studies could be a great tool to better understand the ecology of influenza viruses in nature. PMID:25231137

  19. Interferon-γ Inhibits Ebola Virus Infection

    PubMed Central

    Rhein, Bethany A.; Powers, Linda S.; Rogers, Kai; Anantpadma, Manu; Singh, Brajesh K.; Sakurai, Yasuteru; Bair, Thomas; Miller-Hunt, Catherine; Sinn, Patrick; Davey, Robert A.

    2015-01-01

    Ebola virus outbreaks, such as the 2014 Makona epidemic in West Africa, are episodic and deadly. Filovirus antivirals are currently not clinically available. Our findings suggest interferon gamma, an FDA-approved drug, may serve as a novel and effective prophylactic or treatment option. Using mouse-adapted Ebola virus, we found that murine interferon gamma administered 24 hours before or after infection robustly protects lethally-challenged mice and reduces morbidity and serum viral titers. Furthermore, we demonstrated that interferon gamma profoundly inhibits Ebola virus infection of macrophages, an early cellular target of infection. As early as six hours following in vitro infection, Ebola virus RNA levels in interferon gamma-treated macrophages were lower than in infected, untreated cells. Addition of the protein synthesis inhibitor, cycloheximide, to interferon gamma-treated macrophages did not further reduce viral RNA levels, suggesting that interferon gamma blocks life cycle events that require protein synthesis such as virus replication. Microarray studies with interferon gamma-treated human macrophages identified more than 160 interferon-stimulated genes. Ectopic expression of a select group of these genes inhibited Ebola virus infection. These studies provide new potential avenues for antiviral targeting as these genes that have not previously appreciated to inhibit negative strand RNA viruses and specifically Ebola virus infection. As treatment of interferon gamma robustly protects mice from lethal Ebola virus infection, we propose that interferon gamma should be further evaluated for its efficacy as a prophylactic and/or therapeutic strategy against filoviruses. Use of this FDA-approved drug could rapidly be deployed during future outbreaks. PMID:26562011

  20. Interferon-γ Inhibits Ebola Virus Infection.

    PubMed

    Rhein, Bethany A; Powers, Linda S; Rogers, Kai; Anantpadma, Manu; Singh, Brajesh K; Sakurai, Yasuteru; Bair, Thomas; Miller-Hunt, Catherine; Sinn, Patrick; Davey, Robert A; Monick, Martha M; Maury, Wendy

    2015-01-01

    Ebola virus outbreaks, such as the 2014 Makona epidemic in West Africa, are episodic and deadly. Filovirus antivirals are currently not clinically available. Our findings suggest interferon gamma, an FDA-approved drug, may serve as a novel and effective prophylactic or treatment option. Using mouse-adapted Ebola virus, we found that murine interferon gamma administered 24 hours before or after infection robustly protects lethally-challenged mice and reduces morbidity and serum viral titers. Furthermore, we demonstrated that interferon gamma profoundly inhibits Ebola virus infection of macrophages, an early cellular target of infection. As early as six hours following in vitro infection, Ebola virus RNA levels in interferon gamma-treated macrophages were lower than in infected, untreated cells. Addition of the protein synthesis inhibitor, cycloheximide, to interferon gamma-treated macrophages did not further reduce viral RNA levels, suggesting that interferon gamma blocks life cycle events that require protein synthesis such as virus replication. Microarray studies with interferon gamma-treated human macrophages identified more than 160 interferon-stimulated genes. Ectopic expression of a select group of these genes inhibited Ebola virus infection. These studies provide new potential avenues for antiviral targeting as these genes that have not previously appreciated to inhibit negative strand RNA viruses and specifically Ebola virus infection. As treatment of interferon gamma robustly protects mice from lethal Ebola virus infection, we propose that interferon gamma should be further evaluated for its efficacy as a prophylactic and/or therapeutic strategy against filoviruses. Use of this FDA-approved drug could rapidly be deployed during future outbreaks. PMID:26562011

  1. Dengue Virus Infection Perturbs Lipid Homeostasis in Infected Mosquito Cells

    SciTech Connect

    Perera, Rushika M.; Riley, Catherine; Isaac, Georgis; Hopf- Jannasch, Amber; Moore, Ronald J.; Weitz, Karl K.; Pasa-Tolic, Ljiljana; Metz, Thomas O.; Adamec, Jiri; Kuhn, Richard J.

    2012-03-22

    Dengue virus causes {approx}50-100 million infections per year and thus is considered one of the most aggressive arthropod-borne human pathogen worldwide. During its replication, dengue virus induces dramatic alterations in the intracellular membranes of infected cells. This phenomenon is observed both in human and vector-derived cells. Using high-resolution mass spectrometry of mosquito cells, we show that this membrane remodeling is directly linked to a unique lipid repertoire induced by dengue virus infection. Specifically, 15% of the metabolites detected were significantly different between DENV infected and uninfected cells while 85% of the metabolites detected were significantly different in isolated replication complex membranes. Furthermore, we demonstrate that intracellular lipid redistribution induced by the inhibition of fatty acid synthase, the rate-limiting enzyme in lipid biosynthesis, is sufficient for cell survival but is inhibitory to dengue virus replication. Lipids that have the capacity to destabilize and change the curvature of membranes as well as lipids that change the permeability of membranes are enriched in dengue virus infected cells. Several sphingolipids and other bioactive signaling molecules that are involved in controlling membrane fusion, fission, and trafficking as well as molecules that influence cytoskeletal reorganization are also up regulated during dengue infection. These observations shed light on the emerging role of lipids in shaping the membrane and protein environments during viral infections and suggest membrane-organizing principles that may influence virus-induced intracellular membrane architecture.

  2. Human immunodeficiency virus infection and pneumothorax

    PubMed Central

    Terzi, Eirini; Zarogoulidis, Konstantinos; Kougioumtzi, Ioanna; Dryllis, Georgios; Kioumis, Ioannis; Pitsiou, Georgia; Machairiotis, Nikolaos; Katsikogiannis, Nikolaos; Tsiouda, Theodora; Madesis, Athanasios; Karaiskos, Theodoros

    2014-01-01

    Pneumothorax is a serious and relatively frequent complication of human immunodeficiency virus (HIV) infection that may associate with increased morbidity and mortality and may prove difficult to manage, especially in patients with acquired immunodeficiency syndrome (AIDS). PMID:25337392

  3. METHODS USED TO STUDY RESPIRATORY VIRUS INFECTION

    PubMed Central

    Flaño, Emilio; Jewell, Nancy A.; Durbin, Russell K.; Durbin, Joan E.

    2009-01-01

    This unit describes protocols for infecting the mouse respiratory tract, and assaying virus replication and host response in the lung. Respiratory infections are the leading cause of acute illness worldwide, affecting mostly infants and children in developing countries. The purpose of this unit is to provide the readers with a basic strategy and protocols to study the pathogenesis and immunology of respiratory virus infection using the mouse as an animal model. The procedures include: (i) basic techniques for mouse infection, tissue sampling and preservation, (ii) determination of viral titers, isolation and analysis of lymphocytes and dendritic cells using flow-cytometry, and (iii) lung histology, immunohistochemistry and in situ hybridization. PMID:19499505

  4. Life-Threatening Sochi Virus Infections, Russia.

    PubMed

    Kruger, Detlev H; Tkachenko, Evgeniy A; Morozov, Vyacheslav G; Yunicheva, Yulia V; Pilikova, Olga M; Malkin, Gennadiy; Ishmukhametov, Aydar A; Heinemann, Patrick; Witkowski, Peter T; Klempa, Boris; Dzagurova, Tamara K

    2015-12-01

    Sochi virus was recently identified as a new hantavirus genotype carried by the Black Sea field mouse, Apodemus ponticus. We evaluated 62 patients in Russia with Sochi virus infection. Most clinical cases were severe, and the case-fatality rate was as high as 14.5%. PMID:26584463

  5. Life-Threatening Sochi Virus Infections, Russia

    PubMed Central

    Tkachenko, Evgeniy A.; Morozov, Vyacheslav G.; Yunicheva, Yulia V.; Pilikova, Olga M.; Malkin, Gennadiy; Ishmukhametov, Aydar A.; Heinemann, Patrick; Witkowski, Peter T.; Klempa, Boris; Dzagurova, Tamara K.

    2015-01-01

    Sochi virus was recently identified as a new hantavirus genotype carried by the Black Sea field mouse, Apodemus ponticus. We evaluated 62 patients in Russia with Sochi virus infection. Most clinical cases were severe, and the case-fatality rate was as high as 14.5%. PMID:26584463

  6. Nipah Virus Infection in Dogs, Malaysia, 1999

    PubMed Central

    Alim, Asiah N.M.; Bunning, Michel L.; Lee, Ong Bee; Wagoner, Kent D.; Amman, Brian R.; Stockton, Patrick C.; Ksiazek, Thomas G.

    2009-01-01

    The 1999 outbreak of Nipah virus encephalitis in humans and pigs in Peninsular Malaysia ended with the evacuation of humans and culling of pigs in the epidemic area. Serologic screening showed that, in the absence of infected pigs, dogs were not a secondary reservoir for Nipah virus. PMID:19523300

  7. Chronic Hepatitis E Virus Infection and Treatment

    PubMed Central

    Kamar, Nassim; Izopet, Jacques; Dalton, Harry R.

    2013-01-01

    It is now well accepted that hepatitis E virus (HEV) infection can induce chronic hepatitis and cirrhosis in immunosuppressed patients. Chronic genotype-3 HEV infections were first reported in patients with a solid-organ transplant. Thereafter, cases of chronic HEV infection have been reported in patients with hematological disease and in those who are human immunodeficiency virus (HIV)-positive. HEV-associated extra-hepatic manifestations, including neurological symptoms, kidney injuries, and hematological disorders, have been also reported. In transplant patients, reducing the dosage of immunosuppressive drugs allows the virus to be cleared in some patients. In the remaining patients, as well as hematological patients and patients who are HIV-positive, anti-viral therapies, such as pegylated interferon and ribavirin, have been found to be efficient in eradicating HEV infection. This review summarizes our current knowledge of chronic HEV infection, its treatment, and the extra-hepatic manifestations induced by HEV. PMID:25755487

  8. Virus-Specific Cellular Response in Hepatitis C Virus Infection.

    PubMed

    Kaźmierczak, Justyna; Caraballo Cortes, Kamila; Bukowska-Ośko, Iwona; Radkowski, Marek

    2016-04-01

    Studies performed on chimpanzees and humans have revealed that strong, multispecific and sustained CD4(+) and CD8(+) T cell immune responses is a major determinant of hepatitis C virus (HCV) clearance. However, spontaneous elimination of the virus occurs in minority of infected individuals and cellular response directed against HCV antigens is not persistent in individuals with chronic infection. This review presents characteristics of the HCV-specific T cell response in patients with different clinical course of infection, including acute and chronic infection, persons who spontaneously eliminated HCV and non-infected subjects exposed to HCV. Detection of HCV-specific response, especially in non-infected subjects exposed to HCV, may be indicative of HCV prevalence in population and rate of spontaneous viral clearance. Understanding the mechanisms and role of HCV-specific cellular immune response would contribute to better understanding of HCV epidemiology, immunopathogenesis and may help to design an effective vaccine. PMID:26429740

  9. DIESEL EXHAUST ENHANCES INFLUENZA VIRUS INFECTIONS IN RESPIRATORY EPITHELIAL CELLS

    EPA Science Inventory

    Several factors, such as age and nutritional status can affect the susceptibility to influenza infections. Moreover, exposure to air pollutants, such as diesel exhaust (DE), has been shown to affect respiratory virus infections in rodent models. Influenza virus primarily infects ...

  10. Molecular Biology of Hepatitis B Virus Infection

    PubMed Central

    Seeger, Christoph; Mason, William S.

    2015-01-01

    Human hepatitis B virus (HBV) is the prototype of a family of small DNA viruses that productively infect hepatocytes, the major cell of the liver, and replicate by reverse transcription of a terminally redundant viral RNA, the pregenome. Upon infection, the circular, partially double-stranded virion DNA is converted in the nucleus to a covalently closed circular DNA (cccDNA) that assembles into a minichromosome, the template for viral mRNA synthesis. Infection of hepatocytes is non-cytopathic. Infection of the liver may be either transient (<6 months) or chronic and life long, depending on the ability of the host immune response to clear the infection. Chronic infections can cause immune mediated liver damage progressing to cirrhosis and hepatocellular carcinoma (HCC). The mechanisms of carcinogenesis are unclear. Antiviral therapies with nucleoside analog inhibitors of viral DNA synthesis delay sequelae, but cannot cure HBV infections due to the persistence of cccDNA in hepatocytes. PMID:25759099

  11. Respiratory syncytial virus infection in cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine respiratory syncytial virus (bRSV) is a cause of respiratory disease in cattle world-wide. It has an integral role in enzootic pneumonia in young dairy calves and summer pneumonia in nursing beef calves. Furthermore, bRSV infection can predispose calves to secondary bacterial infection by org...

  12. Preventing hospitalizations for respiratory syncytial virus infection

    PubMed Central

    Robinson, Joan L; Le Saux, Nicole

    2015-01-01

    Respiratory syncytial virus infection is the leading cause of lower respiratory tract infections in young children. Palivizumab has minimal impact on RSV hospitilization rates as it is only practical to offer it to the highest risk groups. The present statement reviews the published literature and provides updated recommendations regarding palivizumab use in children in Canada. PMID:26435673

  13. Recurrent lumbosacral herpes simplex virus infection

    PubMed Central

    Vassantachart, Janna M.

    2016-01-01

    We present the case of a 54-year-old white woman with episodic lumbosacral lesions that she had been treating as psoriasis. Evaluation revealed classic herpes simplex virus (HSV) infection. The discussion reviews the significance and potential complications of recurrent lumbosacral HSV infection. PMID:26722168

  14. Economics of bovine leukemia virus infection.

    PubMed

    Pelzer, K D

    1997-03-01

    A herd infected with bovine leukemia virus suffers a direct economic loss due to clinical lymphosarcoma. A major indirect cost associated with infection is restriction of the sale of animals and germplasma to foreign markets. Reports on the economic effects of infection on production have been variable and are reviewed in this article. In order to develop cost-effective bovine leukemia virus control programs, costs associated with the disease, the cost of prevention, and expected economic returns from a program need to be considered. PMID:9071750

  15. Human immunodeficiency virus infection and the liver

    PubMed Central

    Crane, Megan; Iser, David; Lewin, Sharon R

    2012-01-01

    Liver disease in human immunodeficiency virus (HIV)-infected individuals encompasses the spectrum from abnormal liver function tests, liver decompensation, with and without evidence of cirrhosis on biopsy, to non-alcoholic liver disease and its more severe form, non-alcoholic steatohepatitis and hepatocellular cancer. HIV can infect multiple cells in the liver, leading to enhanced intrahepatic apoptosis, activation and fibrosis. HIV can also alter gastro-intestinal tract permeability, leading to increased levels of circulating lipopolysaccharide that may have an impact on liver function. This review focuses on recent changes in the epidemiology, pathogenesis and clinical presentation of liver disease in HIV-infected patients, in the absence of co-infection with hepatitis B virus or hepatitis C virus, with a specific focus on issues relevant to low and middle income countries. PMID:22489261

  16. Infection of phytoplankton by aerosolized marine viruses.

    PubMed

    Sharoni, Shlomit; Trainic, Miri; Schatz, Daniella; Lehahn, Yoav; Flores, Michel J; Bidle, Kay D; Ben-Dor, Shifra; Rudich, Yinon; Koren, Ilan; Vardi, Assaf

    2015-05-26

    Marine viruses constitute a major ecological and evolutionary driving force in the marine ecosystems. However, their dispersal mechanisms remain underexplored. Here we follow the dynamics of Emiliania huxleyi viruses (EhV) that infect the ubiquitous, bloom-forming phytoplankton E. huxleyi and show that EhV are emitted to the atmosphere as primary marine aerosols. Using a laboratory-based setup, we showed that the dynamic of EhV aerial emission is strongly coupled to the host-virus dynamic in the culture media. In addition, we recovered EhV DNA from atmospheric samples collected over an E. huxleyi bloom in the North Atlantic, providing evidence for aerosolization of marine viruses in their natural environment. Decay rate analysis in the laboratory revealed that aerosolized viruses can remain infective under meteorological conditions prevailing during E. huxleyi blooms in the ocean, allowing potential dispersal and infectivity over hundreds of kilometers. Based on the combined laboratory and in situ findings, we propose that atmospheric transport of EhV is an effective transmission mechanism for spreading viral infection over large areas in the ocean. This transmission mechanism may also have an important ecological impact on the large-scale host-virus "arms race" during bloom succession and consequently the turnover of carbon in the ocean. PMID:25964340

  17. Infection of phytoplankton by aerosolized marine viruses

    PubMed Central

    Sharoni, Shlomit; Trainic, Miri; Schatz, Daniella; Lehahn, Yoav; Flores, Michel J.; Bidle, Kay D.; Ben-Dor, Shifra; Rudich, Yinon; Vardi, Assaf

    2015-01-01

    Marine viruses constitute a major ecological and evolutionary driving force in the marine ecosystems. However, their dispersal mechanisms remain underexplored. Here we follow the dynamics of Emiliania huxleyi viruses (EhV) that infect the ubiquitous, bloom-forming phytoplankton E. huxleyi and show that EhV are emitted to the atmosphere as primary marine aerosols. Using a laboratory-based setup, we showed that the dynamic of EhV aerial emission is strongly coupled to the host–virus dynamic in the culture media. In addition, we recovered EhV DNA from atmospheric samples collected over an E. huxleyi bloom in the North Atlantic, providing evidence for aerosolization of marine viruses in their natural environment. Decay rate analysis in the laboratory revealed that aerosolized viruses can remain infective under meteorological conditions prevailing during E. huxleyi blooms in the ocean, allowing potential dispersal and infectivity over hundreds of kilometers. Based on the combined laboratory and in situ findings, we propose that atmospheric transport of EhV is an effective transmission mechanism for spreading viral infection over large areas in the ocean. This transmission mechanism may also have an important ecological impact on the large-scale host–virus “arms race” during bloom succession and consequently the turnover of carbon in the ocean. PMID:25964340

  18. Autoimmune pathogenesis in dengue virus infection.

    PubMed

    Lin, Chiou-Feng; Wan, Shu-Wen; Cheng, Hsien-Jen; Lei, Huan-Yao; Lin, Yee-Shin

    2006-01-01

    The pathogenic mechanisms of dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS) caused by dengue virus (DV) infection remain unresolved. Patients with DHF/DSS are characterized by several manifestations, including severe thrombocytopenia, vascular leakage, and hepatomegaly. In addition to the effect of virus load and virus variation, abnormal immune responses of the host after DV infection may also account for the progression of DHF/DSS. Actually, viral autoimmunity is involved in the pathogenesis of numerous viral infections, such as human immunodeficiency virus, human hepatitis C virus, human cytomegalovirus, herpes simplex virus, Epstein- Barr virus, and DV. In this review, we discuss the implications of autoimmunity in dengue pathogenesis. Antibodies directed against DV nonstructural protein 1 (NS1) showed cross-reactivity with human platelets and endothelial cells, which lead to platelet and endothelial cell damage and inflammatory activation. Based on these findings, we hypothesize that anti-DV NS1 is involved in the pathogenesis of DF and DHF/DSS, and this may provide important information in dengue vaccine development. PMID:16817755

  19. Influenza virus infection, ozone exposure, and fibrogenesis.

    PubMed

    Jakab, G J; Bassett, D J

    1990-05-01

    Oxidant exposure following chemically induced lung injury exacerbates the tendency to develop pulmonary fibrosis. Influenza virus pneumonitis causes severe acute lung damage that, upon resolution, is followed by a persistent alveolitis and parenchymal changes characterized by patchy interstitial pneumonia and collagen deposition in the affected areas. To determine whether oxidant exposure exacerbates the virus-induced alveolitis and residual lung damage, mice were infected by aerosol inhalation with influenza A virus and continuously exposed to 0.5 ppm ozone or ambient air. Noninfected control mice were exposed to either ambient air or ozone. On various days during the first month after infection, groups of mice were sacrificed and their lungs assessed for acute injury (lung lavage albumin, total and differential cell counts, wet/dry ratios, and morphometry). At 30, 60, 90, and 120 days after infection, groups of mice were sacrificed for total and differential lavage cell counts, lung hydroxyproline content, and morphometric analysis. Ozone exposure did not alter the proliferation of virus in the lungs as quantitated by infectious virus titers of lung homogenates at 1, 4, 7, 10, and 15 days after virus infection but mitigated the virus-induced acute lung injury by approximately 50%. After Day 30 a shift in the character of the pulmonary lesions was observed in that continuous exposure to ozone potentiated the postinfluenzal alveolitis and structural changes in the lung parenchyma. Additional studies suggest that the mechanism for the enhanced postinfluenzal lung damage may be related to the oxidant impairing the repair process of the acute influenzal lung damage. These data demonstrate that ozone exposure mitigates acute virus-induced lung injury and potentiates residual lung damage. PMID:2339849

  20. The immune response to Nipah virus infection.

    PubMed

    Prescott, Joseph; de Wit, Emmie; Feldmann, Heinz; Munster, Vincent J

    2012-09-01

    Nipah virus has recently emerged as a zoonotic agent that is highly pathogenic in humans. Outbreaks have occurred regularly over the last two decades in South and Southeast Asia, where mortality rates reach as high as 100 %. The natural reservoir of Nipah virus has been identified as bats from the Pteropus family, where infection is largely asymptomatic. Human disease is characterized by both respiratory and encephalitic components, and thus far, no effective vaccine or intervention strategies are available. Little is know about how the immune response of either the reservoir host or incidental hosts responds to infection, and how this immune response is either inadequate or might contribute to disease in the dead-end host. Experimental vaccines strategies have given us some insight into the immunological requirements for protection. This review summarizes our current understanding of the immune response to Nipah virus infection and emphasizes the need for further research. PMID:22669317

  1. Peptide inhibitors of dengue virus and West Nile virus infectivity

    PubMed Central

    Hrobowski, Yancey M; Garry, Robert F; Michael, Scott F

    2005-01-01

    Viral fusion proteins mediate cell entry by undergoing a series of conformational changes that result in virion-target cell membrane fusion. Class I viral fusion proteins, such as those encoded by influenza virus and human immunodeficiency virus (HIV), contain two prominent alpha helices. Peptides that mimic portions of these alpha helices inhibit structural rearrangements of the fusion proteins and prevent viral infection. The envelope glycoprotein (E) of flaviviruses, such as West Nile virus (WNV) and dengue virus (DENV), are class II viral fusion proteins comprised predominantly of beta sheets. We used a physio-chemical algorithm, the Wimley-White interfacial hydrophobicity scale (WWIHS) [1] in combination with known structural data to identify potential peptide inhibitors of WNV and DENV infectivity that target the viral E protein. Viral inhibition assays confirm that several of these peptides specifically interfere with target virus entry with 50% inhibitory concentration (IC50) in the 10 μM range. Inhibitory peptides similar in sequence to domains with a significant WWIHS scores, including domain II (IIb), and the stem domain, were detected. DN59, a peptide corresponding to the stem domain of DENV, inhibited infection by DENV (>99% inhibition of plaque formation at a concentrations of <25 μM) and cross-inhibition of WNV fusion/infectivity (>99% inhibition at <25 μM) was also demonstrated with DN59. However, a potent WNV inhibitory peptide, WN83, which corresponds to WNV E domain IIb, did not inhibit infectivity by DENV. Additional results suggest that these inhibitory peptides are noncytotoxic and act in a sequence specific manner. The inhibitory peptides identified here can serve as lead compounds for the development of peptide drugs for flavivirus infection. PMID:15927084

  2. Parainfluenza Virus 5 Expressing the G Protein of Rabies Virus Protects Mice after Rabies Virus Infection

    PubMed Central

    Huang, Ying; Chen, Zhenhai; Huang, Junhua

    2014-01-01

    Rabies remains a major public health threat around the world. Once symptoms appear, there is no effective treatment to prevent death. In this work, we tested a recombinant parainfluenza virus 5 (PIV5) strain expressing the glycoprotein (G) of rabies (PIV5-G) as a therapy for rabies virus infection: we have found that PIV5-G protected mice as late as 6 days after rabies virus infection. PIV5-G is a promising vaccine for prevention and treatment of rabies virus infection. PMID:25552723

  3. Pathogenesis of human immunodeficiency virus infection.

    PubMed Central

    Levy, J A

    1993-01-01

    The lentivirus human immunodeficiency virus (HIV) causes AIDS by interacting with a large number of different cells in the body and escaping the host immune response against it. HIV is transmitted primarily through blood and genital fluids and to newborn infants from infected mothers. The steps occurring in infection involve an interaction of HIV not only with the CD4 molecule on cells but also with other cellular receptors recently identified. Virus-cell fusion and HIV entry subsequently take place. Following virus infection, a variety of intracellular mechanisms determine the relative expression of viral regulatory and accessory genes leading to productive or latent infection. With CD4+ lymphocytes, HIV replication can cause syncytium formation and cell death; with other cells, such as macrophages, persistent infection can occur, creating reservoirs for the virus in many cells and tissues. HIV strains are highly heterogeneous, and certain biologic and serologic properties determined by specific genetic sequences can be linked to pathogenic pathways and resistance to the immune response. The host reaction against HIV, through neutralizing antibodies and particularly through strong cellular immune responses, can keep the virus suppressed for many years. Long-term survival appears to involve infection with a relatively low-virulence strain that remains sensitive to the immune response, particularly to control by CD8+ cell antiviral activity. Several therapeutic approaches have been attempted, and others are under investigation. Vaccine development has provided some encouraging results, but the observations indicate the major challenge of preventing infection by HIV. Ongoing research is necessary to find a solution to this devastating worldwide epidemic. Images PMID:8464405

  4. Control of viruses infecting grapevine.

    PubMed

    Maliogka, Varvara I; Martelli, Giovanni P; Fuchs, Marc; Katis, Nikolaos I

    2015-01-01

    Grapevine is a high value vegetatively propagated fruit crop that suffers from numerous viruses, including some that seriously affect the profitability of vineyards. Nowadays, 64 viruses belonging to different genera and families have been reported in grapevines and new virus species will likely be described in the future. Three viral diseases namely leafroll, rugose wood, and infectious degeneration are of major economic importance worldwide. The viruses associated with these diseases are transmitted by mealybugs, scale and soft scale insects, or dagger nematodes. Here, we review control measures of the major grapevine viral diseases. More specifically, emphasis is laid on (i) approaches for the production of clean stocks and propagative material through effective sanitation, robust diagnosis, as well as local and regional certification efforts, (ii) the management of vectors of viruses using cultural, biological, and chemical methods, and (iii) the production of resistant grapevines mainly through the application of genetic engineering. The benefits and limitations of the different control measures are discussed with regard to accomplishments and future research directions. PMID:25591880

  5. Marine Viruses that infect Eukaryotic Microalgae.

    PubMed

    Kimura, Kei; Tomaru, Yuji

    2015-01-01

    Marine microalgae, in general, explain large amount of the primary productions on the planet. Their huge biomass through photosynthetic activities is significant to understand the global geochemical cycles. Many researchers are, therefore, focused on studies of marine microalgae, i.e. phytoplankton. Since the first report of high abundance of viruses in the sea at late 1980's, the marine viruses have recognized as an important decreasing factor of its host populations. They seem to be composed of diverse viruses infectious to different organism groups; most of them are considered to be phages infectious to prokaryotes, and viruses infecting microalgae might be ranked in second level. Over the last quarter of a century, the knowledge on marine microalgal viruses has been accumulated in many aspects. Until today, ca. 40 species of marine microalgal viruses have been discovered, including dsDNA, ssDNA, dsRNA and ssRNA viruses. Their features are unique and comprise new ideas and discoveries, indicating that the marine microalgal virus research is still an intriguing unexplored field. In this review, we summarize their basic biology and ecology, and discuss how and what we should research in this area for further progress. PMID:26923956

  6. Adolescents and human immunodeficiency virus infection.

    PubMed

    Anderson, J R

    1992-12-01

    As of March 31, 1992, individuals 13 to 19 years of age had been diagnosed with acquired immunodeficiency syndrome; over one third were diagnosed in the past 2 years alone. Because of the long incubation period from initial infection to acquired immunodeficiency syndrome diagnosis, the majority of young adults with acquired immunodeficiency syndrome were probably initially infected as adolescents. In 1991, 34% of adolescents with acquired immunodeficiency syndrome were female, and their predominant mode of transmission was heterosexual contact. Human immunodeficiency virus seroprevalence studies of adolescents show a male-to-female ratio approaching 1:1, with many human immunodeficiency virus-infected adolescent women identifying none of the standard risk. Factors such as sexual and drug experimentation, risk taking, and sense of invulnerability so characteristic of adolescence put adolescents at special risk for human immunodeficiency virus. There is no published information on if or how clinical manifestations of human immunodeficiency virus disease in adolescents might differ from those seen in adults. Medical care should be broad-based and should include access to clinical trials for new drug treatments. General knowledge levels about acquired immunodeficiency syndrome are high among US adolescents, but behavioral changes have lagged behind. All adolescents should be targeted for intensive education about human immunodeficiency virus along with interventions designed to enhance their general coping, communication, and decision-making skills. PMID:1450349

  7. The neurobiology of varicella zoster virus infection

    PubMed Central

    Gilden, D.; Mahalingam, R.; Nagel, M. A.; Pugazhenthi, S.; Cohrs, R. J.

    2011-01-01

    Varicella zoster virus (VZV) is a neurotropic herpesvirus that infects nearly all humans. Primary infection usually causes chickenpox (varicella), after which virus becomes latent in cranial nerve ganglia, dorsal root ganglia and autonomic ganglia along the entire neuraxis. Although VZV cannot be isolated from human ganglia, nucleic acid hybridization and, later, polymerase chain reaction proved that VZV is latent in ganglia. Declining VZV-specific host immunity decades after primary infection allows virus to reactivate spontaneously, resulting in shingles (zoster) characterized by pain and rash restricted to 1-3 dermatomes. Multiple other serious neurological and ocular disorders also result from VZV reactivation. This review summarizes the current state of knowledge of the clinical and pathological complications of neurological and ocular disease produced by VZV reactivation, molecular aspects of VZV latency, VZV virology and VZV-specific immunity, the role of apoptosis in VZV-induced cell death, and the development of an animal model provided by simian varicella virus infection of monkeys. PMID:21342215

  8. Pathogenesis of Machupo virus infection in primates*

    PubMed Central

    Eddy, G. A.; Scott, S. K.; Wagner, F. S.; Brand, O. M.

    1975-01-01

    Experimental Machupo virus infection of rhesus and cynomolgus monkeys produced a severe illness consisting of an initial clinical phase and a later neurological phase. Cumulative mortality during the two phases was 80% and 95% respectively. Attempts to alter the pathogenesis with decomplementation or immunosuppression resulted in earlier deaths of the monkeys. PMID:182402

  9. Infection of Plants by Tobacco Mosaic Virus.

    ERIC Educational Resources Information Center

    McDaniel, Larry; Maratos, Marina; Farabaugh, Joan

    1998-01-01

    Provides three exercises that introduce high school and college students to a common strain of the tobacco mosaic virus and the study of some basic biological processes. Activities involve inoculation of plants and observing and recording symptom development in infected plants. (DDR)

  10. Mental Status after West Nile Virus Infection

    PubMed Central

    Sadek, Joseph; Pergam, Steven; Echevarria, Leonor A.; Davis, Larry E.; Goade, Diane; Harnar, Joanne; Nofchissey, Robert A.; Sewel, C. Mack; Ettestad, Paul

    2006-01-01

    Mental status after acute West Nile virus infection has not been examined objectively. We compared Telephone Interview for Cognitive Status scores of 116 patients with West Nile fever or West Nile neuroinvasive disease. Mental status was poorer and cognitive complaints more frequent with West Nile neuroinvasive disease (p = 0.005). PMID:16965710

  11. Orf virus infection in sheep or goats.

    PubMed

    Spyrou, V; Valiakos, G

    2015-12-14

    Orf virus, a member of the genus Parapoxvirus, is the causative agent of contagious ecthyma ('Orf'). It is a pathogen with worldwide distribution, causing significant financial losses in livestock production. The disease mainly affects sheep and goats, but various other ruminants and mammals have been reported to be infected as well. It is also a zoonotic disease, affecting mainly people who come in direct or indirect contact with infected animals (e.g. farmers, veterinarians). The disease is usually benign and self-limiting, although in many cases, especially in young animals, it can be persistent and even fatal. Production losses caused by Orf virus are believed to be underestimated, as it is not a notifiable disease. This review of literature presents all latest information regarding the virus; considerations regarding treatment and prevention will be also discussed. PMID:26315771

  12. Lethal Dengue Virus Infection: A Forensic Overview.

    PubMed

    Byard, Roger W

    2016-06-01

    Dengue virus is a single-stranded RNA virus that is a member of the family Flaviviridae, genus Flavivirus. It is usually transmitted by the female Aedes aegypti mosquito. Dengue fever is a febrile illness caused by 1 of 4 serotypes of the virus, which may progress to dengue hemorrhagic fever or dengue shock syndrome. The mortality rate of untreated dengue shock syndrome is more than 20%. The reported incidence has increased 30-fold for the past 50 years with an estimated 50 to 100 million dengue infections globally each year, which includes 22,000 deaths. Because of this rapid increase in numbers, more cases will be seen in forensic mortuaries, with diagnostic problems arising from nonspecific or unusual manifestations. In this review, the clinicopathological features of dengue viral infection are evaluated. Adequate blood and tissue sampling at the time of autopsy is mandatory for successful microbiological identification and characterization. PMID:27093563

  13. Previous infection with a mesogenic strain of Newcastle disease virus affects infection with highly pathogenic avian influenza viruses in chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Avian influenza virus (AIV) and Newcastle disease virus (NDV) are two of the most important viruses affecting poultry worldwide, but little is known on the interactions between these two viruses when infecting birds. In a previous study we found that infection of chickens with a mesogenic strain of...

  14. Update on oral herpes virus infections.

    PubMed

    Balasubramaniam, Ramesh; Kuperstein, Arthur S; Stoopler, Eric T

    2014-04-01

    Oral herpes virus infections (OHVIs) are among the most common mucosal disorders encountered by oral health care providers. These infections can affect individuals at any age, from infants to the elderly, and may cause significant pain and dysfunction. Immunosuppressed patients may be at increased risk for serious and potential life-threatening complications caused by OHVIs. Clinicians may have difficulty in diagnosing these infections because they can mimic other conditions of the oral mucosa. This article provides oral health care providers with clinically relevant information regarding etiopathogenesis, diagnosis, and management of OHVIs. PMID:24655522

  15. Atypical Presentations of Respiratory Syncytial Virus Infection

    PubMed Central

    Al-Maskari, Nawal; Mohsin, Jalila; Al-Maani, Amal; Al-Macki, Nabil; Al-Ismaili, Suad

    2016-01-01

    The respiratory syncytial virus (RSV) usually causes a lower respiratory tract infection in affected patients. RSV has also been infrequently linked to extrapulmonary diseases in children. We report four children who had unusually severe clinical manifestations of RSV infections requiring critical care admission. These patients presented to the Royal Hospital, Muscat, Oman, in December 2013 with acute necrotising encephalopathy (ANE), acute fulminant hepatic failure with encephalopathy, pneumatoceles and croup. A unique presentation of ANE has not previously been reported in association with an RSV infection. All patients had a positive outcome and recovered fully with supportive management. PMID:26909220

  16. Modeling Zika Virus Infection in Pregnancy.

    PubMed

    Mysorekar, Indira U; Diamond, Michael S

    2016-08-01

    There were few studies of Zika virus (ZIKV), a flavivirus, until this past year, when large epidemics in the Americas were accompanied by unexpectedly severe clinical manifestations. Infection in pregnant women has emerged as a major global concern because of its linkage to congenital abnormalities including microcephaly, spontaneous abortion, and intrauterine growth restriction.(1) In addition, ZIKV infection in other age groups has been associated with severe neurologic disease and the Guillain-Barré syndrome.(2) Transmission cycles between humans and Aedes aegypti mosquitoes in urban settings can cause large-scale epidemics of ZIKV infection. Although mosquitoes clearly are the primary cause of ZIKV outbreaks, . . . PMID:27433842

  17. Skin manifestations of West Nile virus infection.

    PubMed

    Del Giudice, P; Schuffenecker, I; Zeller, H; Grelier, M; Vandenbos, F; Dellamonica, P; Counillon, E

    2005-01-01

    West Nile virus (WNV) infection is a potentially lethal arbovirus infection. Many notable outbreaks have occurred during the last few years throughout the world, including Europe and the USA. The severity of the disease is mainly related to the neurological complications. A maculopapular exanthema is reported as a clinical sign of the disease. Recently an outbreak of WNV infection occurred in southern France. Three patients out of 6 had a similar skin roseola-like eruption. The cluster of 3 cases of similar febrile roseola of unexplained cause during the same week led to the diagnosis of the first WNV human outbreak in France for 40 years. PMID:16286745

  18. Immunopathogenesis Versus Protection in Dengue Virus Infections

    PubMed Central

    Rothman, Alan L.; Medin, Carey L.; Friberg, Heather; Currier, Jeffrey R.

    2014-01-01

    Dengue viruses (DENV) are mosquito-borne viruses that cause significant morbidity. The existence of four serotypes of DENV with partial immunologic cross-reactivity creates the opportunity for individuals to experience multiple acute DENV infections over the course of their lifetimes. Research over the past several years has revealed complex interactions between DENV and the human innate and adaptive immune systems that can have either beneficial or detrimental influences on the outcome of infection. Further studies that seek to distinguish protective from pathological immune responses in the context of natural DENV infection as well as clinical trials of candidate DENV vaccines have an important place in efforts to control the global impact of this re-emerging viral disease. PMID:24883262

  19. Immunopathogenesis Versus Protection in Dengue Virus Infections.

    PubMed

    Rothman, Alan L; Medin, Carey L; Friberg, Heather; Currier, Jeffrey R

    2014-03-01

    Dengue viruses (DENV) are mosquito-borne viruses that cause significant morbidity. The existence of four serotypes of DENV with partial immunologic cross-reactivity creates the opportunity for individuals to experience multiple acute DENV infections over the course of their lifetimes. Research over the past several years has revealed complex interactions between DENV and the human innate and adaptive immune systems that can have either beneficial or detrimental influences on the outcome of infection. Further studies that seek to distinguish protective from pathological immune responses in the context of natural DENV infection as well as clinical trials of candidate DENV vaccines have an important place in efforts to control the global impact of this re-emerging viral disease. PMID:24883262

  20. [Laboratory diagnosis of hepatitis C virus infection].

    PubMed

    Huber, K R; Kittl, E; Sebesta, C; Bauer, K

    2000-01-01

    In Austria, the prevalence of hepatitis C virus infections is 0.7% (17). Exclusion of a putative infection as well as diagnosis and continuous monitoring of HCV-disease produce considerable costs for the health system. How many and which patients with HCV infection will acquire life-threatening complications is by far not clear. Also, the causes for viral persistence and liver-complications remain obscure. For certain, complex interactions of viral and immunological mechanisms will determine the individual outcome of the disease (1). These considerations pose decisive demands on clinical diagnostics for HCV infections to be dealt with in detail: methods for qualitative detection of an infection as well as for analysis of subtypes and for quantitative determination of viral copies; monitoring of therapy; estimation of the progress of the disease and/or efficacy of therapy. PMID:11205177

  1. Cells in Dengue Virus Infection In Vivo

    PubMed Central

    Noisakran, Sansanee; Onlamoon, Nattawat; Songprakhon, Pucharee; Hsiao, Hui-Mien; Chokephaibulkit, Kulkanya; Perng, Guey Chuen

    2010-01-01

    Dengue has been recognized as one of the most important vector-borne emerging infectious diseases globally. Though dengue normally causes a self-limiting infection, some patients may develop a life-threatening illness, dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS). The reason why DHF/DSS occurs in certain individuals is unclear. Studies in the endemic regions suggest that the preexisting antibodies are a risk factor for DHF/DSS. Viremia and thrombocytopenia are the key clinical features of dengue virus infection in patients. The amounts of virus circulating in patients are highly correlated with severe dengue disease, DHF/DSS. Also, the disturbance, mainly a transient depression, of hematological cells is a critical clinical finding in acute dengue patients. However, the cells responsible for the dengue viremia are unresolved in spite of the intensive efforts been made. Dengue virus appears to replicate and proliferate in many adapted cell lines, but these in vitro properties are extremely difficult to be reproduced in primary cells or in vivo. This paper summarizes reports on the permissive cells in vitro and in vivo and suggests a hematological cell lineage for dengue virus infection in vivo, with the hope that a new focus will shed light on further understanding of the complexities of dengue disease. PMID:22331984

  2. Reaction of goats to infection with infectious bovine rhinotracheitis virus.

    PubMed

    Wafula, J S; Mushi, E Z; Wamwayi, H

    1985-07-01

    Intranasal exposure of goats to infectious bovine rhinotracheitis virus resulted in mild respiratory disease and virus reisolation from nasal secretions. No disease was produced in goats exposed to the same virus by the genital or ocular routes. There was serological evidence of contact transmission of infection from infected goats to cattle. Virus recrudescence was not detected in goats treated with dexamethasone two months after virus inoculation. PMID:2994191

  3. Virus infection, antiviral immunity, and autoimmunity

    PubMed Central

    Getts, Daniel R.; Chastain, Emily M. L.; Terry, Rachael L.; Miller, Stephen D.

    2014-01-01

    Summary As a group of disorders, autoimmunity ranks as the third most prevalent cause of morbidity and mortality in the Western World. However, the etiology of most autoimmune diseases remains unknown. Although genetic linkage studies support a critical underlying role for genetics, the geographic distribution of these disorders as well as the low concordance rates in monozygotic twins suggest that a combination of other factors including environmental ones are involved. Virus infection is a primary factor that has been implicated in the initiation of autoimmune disease. Infection triggers a robust and usually well-coordinated immune response that is critical for viral clearance. However, in some instances, immune regulatory mechanisms may falter, culminating in the breakdown of self-tolerance, resulting in immune-mediated attack directed against both viral and self-antigens. Traditionally, cross-reactive T-cell recognition, known as molecular mimicry, as well as bystander T-cell activation, culminating in epitope spreading, have been the predominant mechanisms elucidated through which infection may culminate in an T-cell-mediated autoimmune response. However, other hypotheses including virus-induced decoy of the immune system also warrant discussion in regard to their potential for triggering autoimmunity. In this review, we discuss the mechanisms by which virus infection and antiviral immunity contribute to the development of autoimmunity. PMID:23947356

  4. Psoralen inactivation of influenza and herpes simplex viruses and of virus-infected cells

    SciTech Connect

    Redfield, D.C.; Richman, D.D.; Oxman, M.N.; Kronenberg, L.H.

    1981-06-01

    Psoralen compounds covalently bind to nucleic acids when irradiated with long-wavelength ultraviolet light. This treatment can destroy the infectivity of deoxyribonucleic acid and ribonucleic acid viruses. Two psoralen compounds, 4'-hydroxymethyltrioxsalen and 4'-aminomethyltrioxsalen, were used with long-wavelength ultraviolet light to inactivate cell-free herpes simplex and influenza viruses and to render virus-infected cells noninfectious. This method of inactivation was compared with germicidal (short-wavelength) ultraviolet light irradiation. The antigenicity of the treated, virus-infected, antigen-bearing cells was examined by immunofluorescence and radioimmunoassay and by measuring the capacity of the herpes simplex virus-infected cells to stimulate virus-specific lymphocyte proliferation. The infectivity of the virus-infected cells could be totally eliminated without altering their viral antigenicity. The use of psoralen plus long-wavelength ultraviolet light is well suited to the preparation of noninfectious virus antigens and virus antigen-bearing cells for immunological assays.

  5. Human papilloma virus infection and psoriasis: Did human papilloma virus infection trigger psoriasis?

    PubMed Central

    Jain, Sonia P.; Gulhane, Sachin; Pandey, Neha; Bisne, Esha

    2015-01-01

    Psoriasis is an autoimmune chronic inflammatory skin disease known to be triggered by streptococcal and HIV infections. However, human papilloma virus infection (HPV) as a triggering factor for the development of psoriasis has not been reported yet. We, hereby report a case of plaque type with inverse psoriasis which probably could have been triggered by genital warts (HPV infection) and discuss the possible pathomechanisms for their coexistence and its management. PMID:26692619

  6. [A NEW PANDEMIC: ZIKA VIRUS INFECTION].

    PubMed

    Bourée, Patrice

    2016-06-01

    Zika virus is a flavivirus isolated in non human primates in 1647, then in humans 1954 (Uganda). It emerged on Micronesia (island af Yap) in 2007, then in French Polynesia in 2013-2014, in South America (mostly in Brazil and Colombia) in 2015 and in French West Indies in 2016. It is transmitted by the bite of Aedes mosquitoes. Zika virus infection is symptomatic in only 20% of cases and clinical presentation is associated with mild illness. But several neurological complications are reported (as Guillain-Barré syndrome: 48 cases in French Polynesia) and congenital malformations (microcephaly). Laboratory diagnosis is based on virus isolation by PCR. There is no specific treatment or vaccine available against the Zika virs. Prevention is based on measures of protection from mosquitoes bites. PMID:27538321

  7. Rabies virus infection of cultured rat sensory neurons.

    PubMed Central

    Lycke, E; Tsiang, H

    1987-01-01

    The axonal transport of rabies virus (challenge virus strain of fixed virus) was studied in differentiated rat embryonic dorsal root ganglion cells. In addition, we observed the attachment of rabies virus to neuronal extensions and virus production by infected neurons. A compartmentalized cell culture system was used, allowing infection and manipulation of neuronal extensions without exposing the neural soma to the virus. The cultures consisted of 60% large neuronal cells whose extensions exhibited neurofilament structures. Rabies virus demonstrated high binding affinity to unmyelinated neurites, as suggested by assays of virus adsorption and immunofluorescence studies. The rate of axoplasmic transport of virus was 12 to 24 mm/day, including the time required for internalization of the virus into neurites. The virus transport could be blocked by cytochalasin B, vinblastine, and colchicine, none of which negatively affected the production of virus in cells once the infection was established. It was concluded that, for the retrograde transfer of rabies virus by neurites from the periphery to the neuronal soma, the integrity of tubulin- and actin-containing structures is essential. The rat sensory neurons were characterized as permissive, moderately susceptible, but low producers of rabies virus. These neurons were capable of harboring rabies virus for long periods of time and able to release virus into the culture medium without showing any morphological alterations. The involvement of sensory neurons in rabies virus pathogenesis, both in viral transport and as a site for persistent viral infection, is discussed. Images PMID:2441076

  8. A single vertebrate DNA virus protein disarms invertebrate immunity to RNA virus infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Virus-host interactions drive a remarkable diversity of immune responses and countermeasures. While investigating virus-invertebrate host interactions we found that two RNA viruses with broad host ranges, vesicular stomatitis virus (VSV) and Sindbis virus (SINV), were unable to infect certain Lepido...

  9. Hepatitis B virus and hepatitis C virus dual infection

    PubMed Central

    Caccamo, Gaia; Saffioti, Francesca; Raimondo, Giovanni

    2014-01-01

    Hepatitis B virus (HBV) and hepatitis C virus (HCV) share common mode of transmission and both are able to induce a chronic infection. Dual HBV/HCV chronic coinfection is a fairly frequent occurrence, especially in high endemic areas and among individuals at high risk of parenterally transmitted infections. The intracellular interplay between HBV and HCV has not yet been sufficiently clarified, also due to the lack of a proper in vitro cellular model. Longitudinal evaluation of serum HBV DNA and HCV RNA amounts has revealed that complex virological profiles may be present in coinfected patients. Dual HBV/HCV infection has been associated to a severe course of the liver disease and to a high risk of developing hepatocellular carcinoma. Despite the clinical importance, solid evidence and clear guidelines for treatment of this special population are still lacking. This review summarizes the available data on the virological and clinical features as well as the therapeutic options of the dual HBV/HCV infection, and highlights the aspects that need to be better clarified. PMID:25356020

  10. Diagnostic challenges of hepatitis C virus infections.

    PubMed

    Huber, K; Sebesta, C; Worofka, B; Kittl, E; Hofmann, J; Klar, S; Hinterberger, W; Bauer, K

    1998-01-01

    In less than 10 years, tremendous progress has been made in our understanding of the biology of hepatitis C virus. Since it was defined as the causal agent of most hepatitis non-A, non-B infections in 1989, clinical laboratories now have access to powerful new techniques for the diagnosis of infection and control of therapy. Identification of the specific virus strain in the patients as well as measurement of the individual viral load and the prediction of a possible therapeutic success have become routine procedures. This effort is warranted because the treatment options are still limited, with alpha-interferon being the only approved drug. No new treatment regimens have emerged yet from the wealth of data from subtyping and quantitating. PMID:15094859

  11. Chaperones in hepatitis C virus infection

    PubMed Central

    Khachatoorian, Ronik; French, Samuel W

    2016-01-01

    The hepatitis C virus (HCV) infects approximately 3% of the world population or more than 185 million people worldwide. Each year, an estimated 350000-500000 deaths occur worldwide due to HCV-associated diseases including cirrhosis and hepatocellular carcinoma. HCV is the most common indication for liver transplantation in patients with cirrhosis worldwide. HCV is an enveloped RNA virus classified in the genus Hepacivirus in the Flaviviridae family. The HCV viral life cycle in a cell can be divided into six phases: (1) binding and internalization; (2) cytoplasmic release and uncoating; (3) viral polyprotein translation and processing; (4) RNA genome replication; (5) encapsidation (packaging) and assembly; and (6) virus morphogenesis (maturation) and secretion. Many host factors are involved in the HCV life cycle. Chaperones are an important group of host cytoprotective molecules that coordinate numerous cellular processes including protein folding, multimeric protein assembly, protein trafficking, and protein degradation. All phases of the viral life cycle require chaperone activity and the interaction of viral proteins with chaperones. This review will present our current knowledge and understanding of the role of chaperones in the HCV life cycle. Analysis of chaperones in HCV infection will provide further insights into viral/host interactions and potential therapeutic targets for both HCV and other viruses. PMID:26783419

  12. Mechanisms of Zika Virus Infection and Neuropathogenesis.

    PubMed

    Olagnier, David; Muscolini, Michela; Coyne, Carolyn B; Diamond, Michael S; Hiscott, John

    2016-08-01

    A spotlight has been focused on the mosquito-borne Zika virus (ZIKV) because of its epidemic outbreak in Brazil and Latin America, as well as the severe neurological manifestations of microcephaly and Guillain-Barré syndrome associated with infection. In this review, we discuss the recent literature on ZIKV-host interactions, including new mechanistic insight concerning the basis of ZIKV-induced neuropathogenesis. PMID:27348136

  13. Vaccinia virus infections in martial arts gym, Maryland, USA, 2008.

    PubMed

    Hughes, Christine M; Blythe, David; Li, Yu; Reddy, Ramani; Jordan, Carol; Edwards, Cindy; Adams, Celia; Conners, Holly; Rasa, Catherine; Wilby, Sue; Russell, Jamaal; Russo, Kelly S; Somsel, Patricia; Wiedbrauk, Danny L; Dougherty, Cindy; Allen, Christopher; Frace, Mike; Emerson, Ginny; Olson, Victoria A; Smith, Scott K; Braden, Zachary; Abel, Jason; Davidson, Whitni; Reynolds, Mary; Damon, Inger K

    2011-04-01

    Vaccinia virus is an orthopoxvirus used in the live vaccine against smallpox. Vaccinia virus infections can be transmissible and can cause severe complications in those with weakened immune systems. We report on a cluster of 4 cases of vaccinia virus infection in Maryland, USA, likely acquired at a martial arts gym. PMID:21470473

  14. Vaccination against bovine herpes mammillitis virus infections in guinea pigs.

    PubMed

    Smee, D F; Leonhardt, J A

    1994-01-01

    Bovine herpes mammillitis virus or bovine herpesvirus type 2 (BHV-2) causes ulcerative lesions on the teats and udders of infected cows. Since no commercial vaccine is available for this disease, we investigated certain experimental BHV-2 vaccines against this virus in infected guinea pigs. Vaginally infected guinea pigs get severe, self-limiting vaginal infections characterized by erythema and swelling and the production of measurable vaginal virus titers. Two vaccine approaches were investigated: vaccination with wild-type (WT) virus by the subcutaneous route, and vaccination either subcutaneously or intravaginally with a thymidine kinase (TK) deficient (TK-) virus. The TK- strain was prepared by passage of BHV-2 in the presence of the potent TK-dependent antiviral agent 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-methyluracil (FMAU). The antiviral activity of FMAU against the virus in plaque reduction assays changed from 0.05 to 2 microM at the same time that the TK activity of the mutant virus decrease to 7% of WT virus TK activity. Subcutaneous vaccination of guinea pigs with WT and TK- viruses did not induce vaginal infection. Primary vaginal infection (vaccination) with the TK- virus led to greatly reduced lesion severity compared to vaginal infection with the WT virus. However, the amount of vaginal virus titers recovered during these primary infections was similar for both TK- and WT viruses, indicating that both viruses had equal infecting potential. Thirty days after vaccination the animals were re-infected intravaginally with WT virus. The vaccinated animals showed dramatically reduced lesion severity and low recoverable virus titers compared to age-matched nonvaccinated animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7928285

  15. Clinical and biological differences between recurrent herpes simplex virus and varicella-zoster virus infections

    SciTech Connect

    Straus, S.E. )

    1989-12-01

    The major features that distinguish recurrent herpes simplex virus infections from zoster are illustrated in this article by two case histories. The clinical and epidemiologic features that characterize recurrent herpes simplex virus and varicella-zoster virus infections are reviewed. It is noted that herpesvirus infections are more common and severe in patients with cellular immune deficiency. Each virus evokes both humoral and cellular immune response in the course of primary infection. DNA hybridization studies with RNA probes labelled with sulfur-35 indicate that herpes simplex viruses persist within neurons, and that varicella-zoster virus is found in the satellite cells that encircle the neurons.

  16. Vaccinia Virus Infection Requires Maturation of Macropinosomes.

    PubMed

    Rizopoulos, Zaira; Balistreri, Giuseppe; Kilcher, Samuel; Martin, Caroline K; Syedbasha, Mohammedyaseen; Helenius, Ari; Mercer, Jason

    2015-08-01

    The prototypic poxvirus, vaccinia virus (VACV), occurs in two infectious forms, mature virions (MVs) and extracellular virions (EVs). Both enter HeLa cells by inducing macropinocytic uptake. Using confocal microscopy, live-cell imaging, targeted RNAi screening and perturbants of endosome maturation, we analyzed the properties and maturation pathway of the macropinocytic vacuoles containing VACV MVs in HeLa cells. The vacuoles first acquired markers of early endosomes [Rab5, early endosome antigen 1 and phosphatidylinositol(3)P]. Prior to release of virus cores into the cytoplasm, they contained markers of late endosomes and lysosomes (Rab7a, lysosome-associated membrane protein 1 and sorting nexin 3). RNAi screening of endocytic cell factors emphasized the importance of late compartments for VACV infection. Follow-up perturbation analysis showed that infection required Rab7a and PIKfyve, confirming that VACV is a late-penetrating virus dependent on macropinosome maturation. VACV EV infection was inhibited by depletion of many of the same factors, indicating that both infectious particle forms share the need for late vacuolar conditions for penetration. PMID:25869659

  17. Chronic hepatitis B virus infection.

    PubMed

    McMahon, Brian J

    2014-01-01

    All providers, regardless of specialty, should perform screening for HBV on high-risk persons, especially those born in endemic countries. The primary care physician can perform the initial evaluation and follow-up of patients with chronic HBV by following the algorithm in this article and consulting with specialists when appropriate. Chronically infected patients should be followed on a regular basis, preferably every 6 months, with liver function tests, and when appropriate, HBV DNA levels. Those who meet the criteria for high risk for HCC should undergo liver ultrasound every 6 months. Powerful antiviral medications are available that can suppress but not cure HBV and result in resolution of liver inflammation and fibrosis, even cirrhosis, as well as decrease the risk of developing HCC. They should be used in those patients who meet the criteria outlined in the practice guidelines of the major liver societies. PMID:24266913

  18. Herd immunity and fatal cases of influenza among the population exposed to poultry and wild birds in Russian Asia in 2013-2014.

    PubMed

    Ilyicheva, Tatyana; Abdurashitov, Murat; Durymanov, Alexander; Susloparov, Ivan; Goncharova, Natalya; Kolosova, Natalya; Mikheev, Valery; Ryzhikov, Alexander

    2016-01-01

    In total 1,525 blood serum samples were collected in October, 2013 in Russian Asia from people who reside in territories that are at high risk for emergence of influenza viruses with pandemic potential. Presence of antibodies to influenza viruses in the sera was tested in hemagglutination inhibition test. None of the samples produced positive results with the antigens A/H5 and A/H7. Twelve strains of influenza A(H1N1pdm09) virus were isolated from people who died presumably from influenza during 2013-2014 epidemic season. All strains were similar to vaccine strain A/California/07/09 according to their antigenic properties and sensitivity to anti-neuraminidase drugs (oseltamivir and zanamivir). Genetic analysis revealed that all strains belong to group 6, subgroup 6B of influenza A(H1N1)pdm09 virus. Substitutions in HA1: S164F add E235K as well as E47G, A86V, K331R, N386K, N397K in NA, and K131E, N29S in NS1, and N29S, R34Q in NEP separate investigated strains into two groups: 1st group-A/Chita/1114/2014, A/Chita/1115/2014, A/Chita/853/2014, A/Barnaul/269/2014 and 2nd group-A/Chita/655/2014, A/Chita/656/2014, A/Chita/709/2014, A/Chita/873/2014. Mutation D222G in HA1, which is often associated with high morbidity of the illness, was present in strain A/Novosibirsk/114/2014. Substitution N386K in NA removes a potential N-glycosylation site in neuraminidases of A/Chita/1114/2014, A/Chita/1115/2014, A/Chita/853/2014, A/Barnaul/269/2014, A/Novosibirsk/114/2014, and A/Blagoveshensk/252/2014. PMID:26105790

  19. Activity of andrographolide against chikungunya virus infection

    PubMed Central

    Wintachai, Phitchayapak; Kaur, Parveen; Lee, Regina Ching Hua; Ramphan, Suwipa; Kuadkitkan, Atichat; Wikan, Nitwara; Ubol, Sukathida; Roytrakul, Sittiruk; Chu, Justin Jang Hann; Smith, Duncan R.

    2015-01-01

    Chikungunya virus (CHIKV) is a re-emerging mosquito-borne alphavirus that has recently engendered large epidemics around the world. There is no specific antiviral for treatment of patients infected with CHIKV, and development of compounds with significant anti-CHIKV activity that can be further developed to a practical therapy is urgently required. Andrographolide is derived from Andrographis paniculata, a herb traditionally used to treat a number of conditions including infections. This study sought to determine the potential of andrographolide as an inhibitor of CHIKV infection. Andrographolide showed good inhibition of CHIKV infection and reduced virus production by approximately 3log10 with a 50% effective concentration (EC50) of 77 μM without cytotoxicity. Time-of-addition and RNA transfection studies showed that andrographolide affected CHIKV replication and the activity of andrographolide was shown to be cell type independent. This study suggests that andrographolide has the potential to be developed further as an anti-CHIKV therapeutic agent. PMID:26384169

  20. Activity of andrographolide against chikungunya virus infection.

    PubMed

    Wintachai, Phitchayapak; Kaur, Parveen; Lee, Regina Ching Hua; Ramphan, Suwipa; Kuadkitkan, Atichat; Wikan, Nitwara; Ubol, Sukathida; Roytrakul, Sittiruk; Chu, Justin Jang Hann; Smith, Duncan R

    2015-01-01

    Chikungunya virus (CHIKV) is a re-emerging mosquito-borne alphavirus that has recently engendered large epidemics around the world. There is no specific antiviral for treatment of patients infected with CHIKV, and development of compounds with significant anti-CHIKV activity that can be further developed to a practical therapy is urgently required. Andrographolide is derived from Andrographis paniculata, a herb traditionally used to treat a number of conditions including infections. This study sought to determine the potential of andrographolide as an inhibitor of CHIKV infection. Andrographolide showed good inhibition of CHIKV infection and reduced virus production by approximately 3log10 with a 50% effective concentration (EC50) of 77 μM without cytotoxicity. Time-of-addition and RNA transfection studies showed that andrographolide affected CHIKV replication and the activity of andrographolide was shown to be cell type independent. This study suggests that andrographolide has the potential to be developed further as an anti-CHIKV therapeutic agent. PMID:26384169

  1. KINETIC PROFILE OF INFLUENZA VIRUS INFECTION IN THREE RAT STRAINS

    EPA Science Inventory

    Abstract

    Influenza infection is a respiratory disease of viral origin that can cause major epidemics in man. The influenza virus infects and damages epithelial cells of the respiratory tract and causes pneumonia. Lung lesions of mice infected with influenza virus resembl...

  2. Respiratory Syncytial Virus Infection (RSV): Transmission and Prevention

    MedlinePlus

    ... CDC Cancel Submit Search The CDC Respiratory Syncytial Virus Infection (RSV) Note: Javascript is disabled or is ... school or childcare. They can then transmit the virus to other members of the family. RSV can ...

  3. Hepatitis B virus infection in immigrant populations

    PubMed Central

    Coppola, Nicola; Alessio, Loredana; Pisaturo, Mariantonietta; Macera, Margherita; Sagnelli, Caterina; Zampino, Rosa; Sagnelli, Evangelista

    2015-01-01

    Hepatitis B virus (HBV) is the most common cause of hepatitis worldwide, with nearly 350 million people chronically infected and 600000 deaths per year due to acute liver failure occurring during acute hepatitis or, more frequently, in HBV-related liver cirrhosis or hepatocellular carcinoma. Ongoing immigration from countries with a high HBV endemicity to those with a low HBV endemicity warrants particular attention to prevent the spread of HBV infection to the native population. This review article analyzes the epidemiology and virological and clinical characteristics of HBV infection in immigrant populations and in their host countries, and suggests prophylactic measures to prevent the spread of this infection. Among the immigrants from different geographical areas, those from South East Asia and sub-Saharan Africa show the highest prevalences of hepatitis B surface antigen (HBsAg) carriers, in accordance with the high endemicity of the countries of origin. The molecular characteristics of HBV infection in immigrants reflect those of the geographical areas of origin: HBV genotype A and D predominate in immigrants from Eastern Europe, B and C in those from Asia and genotype E in those from Africa. The literature data on the clinical course and treatment of HBsAg-positive immigrants are scanty. The management of HBV infection in immigrant populations is difficult and requires expert personnel and dedicated structures for their assistance. The social services, voluntary operators and cultural mediators are essential to achieve optimized psychological and clinical intervention. PMID:26730274

  4. Acute Human Inkoo and Chatanga Virus Infections, Finland

    PubMed Central

    Kantele, Anu; Levanov, Lev; Kivistö, Ilkka; Brummer-Korvenkontio, Markus; Vaheri, Antti; Vapalahti, Olli

    2016-01-01

    Inkoo virus (INKV) and Chatanga virus (CHATV), which are circulating in Finland, are mosquitoborne California serogroup orthobunyaviruses that have a high seroprevalence among humans. Worldwide, INKV infection has been poorly described, and CHATV infection has been unknown. Using serum samples collected in Finland from 7,961 patients suspected of having viral neurologic disease or Puumala virus infection during the summers of 2001–2013, we analyzed the samples to detect California serogroup infections. IgM seropositivity revealed 17 acute infections, and cross-neutralization tests confirmed presence of INKV or CHATV infections. All children (<16 years of age) with INKV infection were hospitalized; adults were outpatients with mild disease, except for 1 who was hospitalized with CHATV infection. Symptoms included fever, influenza-like illness, nausea or vomiting, disorientation, nuchal rigidity, headache, drowsiness, and seizures. Although many INKV and CHATV infections appear to be subclinical, these viruses can cause more severe disease, especially in children. PMID:27088268

  5. Phosphatidylinositol inhibits respiratory syncytial virus infection

    PubMed Central

    Numata, Mari; Kandasamy, Pitchaimani; Nagashima, Yoji; Fickes, Rachel; Murphy, Robert C.; Voelker, Dennis R.

    2015-01-01

    Respiratory syncytial virus (RSV) infects nearly all children under age 2, and reinfection occurs throughout life, seriously impacting adults with chronic pulmonary diseases. Recent data demonstrate that the anionic pulmonary surfactant lipid phosphatidylglycerol (PG) exerts a potent antiviral effect against RSV in vitro and in vivo. Phosphatidylinositol (PI) is also an anionic pulmonary surfactant phospholipid, and we tested its antiviral activity. PI liposomes completely suppress interleukin-8 production from BEAS2B epithelial cells challenged with RSV. The presence of PI during viral challenge in vitro reduces infection by a factor of >103. PI binds RSV with high affinity, preventing virus attachment to epithelial cells. Intranasal inoculation with PI along with RSV in mice reduces the viral burden 30-fold, eliminates the influx of inflammatory cells, and reduces tissue histopathology. Pharmacological doses of PI persist for >6 h in mouse lung. Pretreatment of mice with PI at 2 h prior to viral infection effectively suppresses inflammation and reduces the viral burden by 85%. These data demonstrate that PI has potent antiviral properties, a long residence time in the extracellular bronchoalveolar compartment, and a significant prophylaxis window. The findings demonstrate PG and PI have complementary roles as intrinsic, innate immune antiviral mediators in the lung. PMID:25561461

  6. Vaccines for herpes simplex virus infections.

    PubMed

    Koelle, David M

    2006-02-01

    Infections with herpes simplex virus (HSV) type 1 (HSV-1) and type 2 (HSV-2) can have serious medical consequences. Although antiviral medications can suppress symptomatic disease, asymptomatic shedding and transmission, they neither cure nor alter the natural history of HSV infections. Manipulation of the immune response is one potential method to decrease disease burden. Current research on prophylactic and therapeutic vaccination approaches is discussed in this review, with a focus on compounds that have entered clinical trials or that display novel compositions or proposed mechanisms of action. One such vaccine is an alum and monophosphoryl lipid A-adjuvanted subunit glycoprotein D2 vaccine that has demonstrated activity in the prevention of HSV-2 infection and disease in HSV-uninfected women in a phase III clinical trial. Further confirmatory clinical trials of this vaccine are currently underway. Other vaccine formats also in development include attenuated live or replication-incompetent HSV-2 strains and technologies that target virus-specific CD8 T-cell responses. PMID:16499283

  7. Therapy and prophylaxis of Ebola virus infections.

    PubMed

    Feldmann, Heinz; Jones, Steven M; Schnittler, Hans-Joachim; Geisbert, Thomas

    2005-08-01

    The first cases of Ebola hemorrhagic fever were reported from Sudan and Zaire (now Democratic Republic of the Congo) in 1976, but the virus has only received significant attention since 1995. Until recently, the development of therapeutics or vaccines was not considered a priority. The knowledge gained during the past decade on the biology and pathogenesis of Ebola virus has led to the development of therapeutic strategies that are currently being investigated. Considering the aggressive nature of Ebola infections, in particular the rapid and overwhelming viral burdens, early diagnosis will play a significant role in determining the success of any intervention strategy. Advanced understanding of the immune response has produced several vaccine candidates of which a few can be considered for further evaluation. This review will summarize and discuss the current therapeutic and prophylactic strategies for Ebola hemorrhagic fever. PMID:16121689

  8. Schmallenberg virus experimental infection of sheep.

    PubMed

    Wernike, Kerstin; Hoffmann, Bernd; Bréard, Emmanuel; Bøtner, Anette; Ponsart, Claire; Zientara, Stéphan; Lohse, Louise; Pozzi, Nathalie; Viarouge, Cyril; Sarradin, Pierre; Leroux-Barc, Céline; Riou, Mickael; Laloy, Eve; Breithaupt, Angele; Beer, Martin

    2013-10-25

    Since late 2011, a novel orthobunyavirus, named Schmallenberg virus (SBV), has been implicated in many cases of severely malformed bovine and ovine offspring in Europe. In adult cattle, SBV is known to cause a mild transient disease; clinical signs include short febrile episodes, decreased milk production and diarrhoea for a few days. However, the knowledge about clinical signs and pathogenesis in adult sheep is limited. In the present study, adult sheep of European domestic breeds were inoculated with SBV either as cell culture grown virus or as virus with no history of passage in cell cultures. Various experimental set-ups were used. Sampling included blood collection at different time points during the experimental period and selected organ material at autopsy. Data from this study showed, that the RNAemic period in sheep was as short as reported for cattle; viral genome was detectable for about 3-5 days by real-time RT-PCR. In total, 13 out of 30 inoculated sheep became RNAemic, with the highest viral load in animals inoculated with virus from low cell culture passaged or the animal passaged material. Contact animals remained negative throughout the study. One RNAemic sheep showed diarrhoea for several days, but fever was not recorded in any of the animals. Antibodies were first detectable 10-14 days post inoculation. Viral RNA was detectable in spleen and lymph nodes up to day 44 post inoculation. In conclusion, as described for cattle, SBV-infection in adult sheep predominantly results in subclinical infection, transient RNAemia and a specific antibody response. Maintenance of viral RNA in the lymphoreticular system is observed for an extended period. PMID:23972950

  9. Bacterial Respiratory Infections Complicating Human Immunodeficiency Virus.

    PubMed

    Feldman, Charles; Anderson, Ronald

    2016-04-01

    Opportunistic bacterial and fungal infections of the lower respiratory tract, most commonly those caused by Streptococcus pneumoniae (the pneumococcus), Mycobacterium tuberculosis, and Pneumocystis jirovecii, remain the major causes of mortality in those infected with human immunodeficiency virus (HIV). Bacterial respiratory pathogens most prevalent in those infected with HIV, other than M. tuberculosis, represent the primary focus of the current review with particular emphasis on the pneumococcus, the leading cause of mortality due to HIV infection in the developed world. Additional themes include (1) risk factors; (2) the predisposing effects of HIV-mediated suppression on pulmonary host defenses, possibly intensified by smoking; (3) clinical and laboratory diagnosis, encompassing assessment of disease severity and outcome; and (4) antibiotic therapy. The final section addresses current recommendations with respect to pneumococcal immunization in the context of HIV infection, including an overview of the rationale underpinning the current "prime-boost" immunization strategy based on sequential administration of pneumococcal conjugate vaccine 13 and pneumococcal polysaccharide vaccine 23. PMID:26974299

  10. Hepatitis B virus infection in Indonesia

    PubMed Central

    Yano, Yoshihiko; Utsumi, Takako; Lusida, Maria Inge; Hayashi, Yoshitake

    2015-01-01

    Approximately 240 million people are chronically infected with hepatitis B virus (HBV), 75% of whom reside in Asia. Approximately 600000 of infected patients die each year due to HBV-related diseases or hepatocellular carcinoma (HCC). The endemicity of hepatitis surface antigen in Indonesia is intermediate to high with a geographical difference. The risk of HBV infection is high in hemodialysis (HD) patients, men having sex with men, and health care workers. Occult HBV infection has been detected in various groups such as blood donors, HD patients, and HIV-infected individuals and children. The most common HBV subgenotype in Indonesia is B3 followed by C1. Various novel subgenotypes of HBV have been identified throughout Indonesia, with the novel HBV subgenotypes C6-C16 and D6 being successfully isolated. Although a number of HBV subgenotypes have been discovered in Indonesia, genotype-related pathogenicity has not yet been elucidated in detail. Therefore, genotype-related differences in the prognosis of liver disease and their effects on treatments need to be determined. A previous study conducted in Indonesia revealed that hepatic steatosis was associated with disease progression. Pre-S2 mutations and mutations at C1638T and T1753V in HBV/B3 have been associated with advanced liver diseases including HCC. However, drug resistance to lamivudine, which is prominent in Indonesia, remains obscure. Although the number of studies on HBV in Indonesia has been increasing, adequate databases on HBV infection are limited. We herein provided an overview of the epidemiology and clinical characteristics of HBV infection in Indonesia. PMID:26478663

  11. Respiratory syncytial virus infection in elderly adults.

    PubMed

    Falsey, Ann R; Walsh, Edward E

    2005-01-01

    Respiratory syncytial virus (RSV) infection is now recognised as a significant problem in elderly adults. Epidemiological evidence indicates the impact of RSV in older adults may be similar to non-pandemic influenza, both in the community and in long-term care facilities. Attack rates in nursing homes are approximately 5-10% per year with significant rates of pneumonia (10-20%) and death (2-5%). Estimates using US health care databases and viral surveillance results over a 9-year period indicate that RSV infection causes approximately 10,000 all-cause deaths annually among persons >64 years of age. In contrast, influenza A accounted for approximately 37,000 yearly deaths in the same age group. The clinical features of RSV infection may be difficult to distinguish from those of influenza but include nasal congestion, cough, wheezing and low-grade fever. Older persons with underlying heart and lung disease and immunocompromised patients are at highest risk for RSV infection-related pneumonia and death. Diagnosis of RSV infection in adults is difficult because viral culture and antigen detection are insensitive, presumably because of low viral titres. The combination of serology and reverse transcriptase polymerase chain reaction assay offers the best sensitivity and specificity for the diagnosis of RSV but unfortunately these techniques are not widely available; consequently, most adult RSV disease goes unrecognised. Although treatment of RSV infection in the elderly is largely supportive, early therapy with ribavirin and intravenous gamma-globulin improves survival in immunocompromised persons. An effective RSV vaccine has not yet been developed. Therefore, prevention of RSV is limited to standard infection control practices, such as hand washing and the use of gowns and gloves. PMID:16038573

  12. Dynamics of perinatal bovine leukemia virus infection

    PubMed Central

    2014-01-01

    Background Bovine leukemia virus (BLV) is highly endemic in many countries, including Argentina. As prevention of the spread from infected animals is of primary importance in breaking the cycle of BLV transmission, it is important to know the pathophysiology of BLV infection in young animals, as they are the main source of animal movement. In this work, we determined the proviral load and antibody titers of infected newborn calves from birth to first parturition (36 months). Results All calves under study were born to infected dams with high proviral load (PVL) in blood and high antibody titers and detectable provirus in the colostrum. The PVL for five out of seven calves was low at birth. All animals reached PVLs of more than 1% infected peripheral blood mononuclear cells (PBMCs), three at 3 months, one at 6 months, and one at 12 months. High PVLs persisted until the end of the study, and, in two animals, exceeded one BLV copy per cell. Two other calves maintained a high PVL from birth until the end of the study. Antibody titers were 32 or higher in the first sample from six out of seven calves. These decayed at 3–6 months to 16 or lower, and then increased again after this point. Conclusions Calves infected during the first week of life could play an active role in early propagation of BLV to susceptible animals, since their PVL raised up during the first 12 months and persist as high for years. Early elimination could help to prevent transmission to young susceptible animals and to their own offspring. To our knowledge, this is the first study of the kinetics of BLV proviral load and antibody titers in newborn infected calves. PMID:24708791

  13. Influenza vaccine effectiveness in adults 65 years and older, Denmark, 2015/16 - a rapid epidemiological and virological assessment.

    PubMed

    Emborg, Hanne Dorthe; Krause, Tyra Grove; Nielsen, Lene; Thomsen, Marianne Kragh; Christiansen, Claus Bohn; Skov, Marianne Nielsine; Nielsen, Xiaohui Chen; Weinreich, Lenette Sandborg; Fischer, Thea Kølsen; Rønn, Jesper; Trebbien, Ramona

    2016-04-01

    In Denmark, both influenza A(H1N1)pdm09 and influenza B co-circulated in the 2015/16 season. We estimated the vaccine effectiveness (VE) of the trivalent influenza vaccine in patients 65 years and older using the test-negative case-control design. The adjusted VE against influenza A(H1N1)pdm09 was 35.0% (95% confidence interval (CI): 11.1-52.4) and against influenza B 4.1% (95% CI: -22.0 to 24.7). The majority of influenza A(H1N1)pdm09 circulating in 2015/16 belonged to the new genetic subgroup subclade 6B.1. PMID:27101732

  14. Zika Virus Infects Human Placental Macrophages.

    PubMed

    Quicke, Kendra M; Bowen, James R; Johnson, Erica L; McDonald, Circe E; Ma, Huailiang; O'Neal, Justin T; Rajakumar, Augustine; Wrammert, Jens; Rimawi, Bassam H; Pulendran, Bali; Schinazi, Raymond F; Chakraborty, Rana; Suthar, Mehul S

    2016-07-13

    The recent Zika virus (ZIKV) outbreak in Brazil has been directly linked to increased cases of microcephaly in newborns. Current evidence indicates that ZIKV is transmitted vertically from mother to fetus. However, the mechanism of intrauterine transmission and the cell types involved remain unknown. We demonstrate that the contemporary ZIKV strain PRVABC59 (PR 2015) infects and replicates in primary human placental macrophages, called Hofbauer cells, and to a lesser extent in cytotrophoblasts, isolated from villous tissue of full-term placentae. Viral replication coincides with induction of type I interferon (IFN), pro-inflammatory cytokines, and antiviral gene expression, but with minimal cell death. Our results suggest a mechanism for intrauterine transmission in which ZIKV gains access to the fetal compartment by directly infecting placental cells and disrupting the placental barrier. PMID:27247001

  15. Honey Bee Infecting Lake Sinai Viruses

    PubMed Central

    Daughenbaugh, Katie F.; Martin, Madison; Brutscher, Laura M.; Cavigli, Ian; Garcia, Emma; Lavin, Matt; Flenniken, Michelle L.

    2015-01-01

    Honey bees are critical pollinators of important agricultural crops. Recently, high annual losses of honey bee colonies have prompted further investigation of honey bee infecting viruses. To better characterize the recently discovered and very prevalent Lake Sinai virus (LSV) group, we sequenced currently circulating LSVs, performed phylogenetic analysis, and obtained images of LSV2. Sequence analysis resulted in extension of the LSV1 and LSV2 genomes, the first detection of LSV4 in the US, and the discovery of LSV6 and LSV7. We detected LSV1 and LSV2 in the Varroa destructor mite, and determined that a large proportion of LSV2 is found in the honey bee gut, suggesting that vector-mediated, food-associated, and/or fecal-oral routes may be important for LSV dissemination. Pathogen-specific quantitative PCR data, obtained from samples collected during a small-scale monitoring project, revealed that LSV2, LSV1, Black queen cell virus (BQCV), and Nosema ceranae were more abundant in weak colonies than strong colonies within this sample cohort. Together, these results enhance our current understanding of LSVs and illustrate the importance of future studies aimed at investigating the role of LSVs and other pathogens on honey bee health at both the individual and colony levels. PMID:26110586

  16. Honey Bee Infecting Lake Sinai Viruses.

    PubMed

    Daughenbaugh, Katie F; Martin, Madison; Brutscher, Laura M; Cavigli, Ian; Garcia, Emma; Lavin, Matt; Flenniken, Michelle L

    2015-06-01

    Honey bees are critical pollinators of important agricultural crops. Recently, high annual losses of honey bee colonies have prompted further investigation of honey bee infecting viruses. To better characterize the recently discovered and very prevalent Lake Sinai virus (LSV) group, we sequenced currently circulating LSVs, performed phylogenetic analysis, and obtained images of LSV2. Sequence analysis resulted in extension of the LSV1 and LSV2 genomes, the first detection of LSV4 in the US, and the discovery of LSV6 and LSV7. We detected LSV1 and LSV2 in the Varroa destructor mite, and determined that a large proportion of LSV2 is found in the honey bee gut, suggesting that vector-mediated, food-associated, and/or fecal-oral routes may be important for LSV dissemination. Pathogen-specific quantitative PCR data, obtained from samples collected during a small-scale monitoring project, revealed that LSV2, LSV1, Black queen cell virus (BQCV), and Nosema ceranae were more abundant in weak colonies than strong colonies within this sample cohort. Together, these results enhance our current understanding of LSVs and illustrate the importance of future studies aimed at investigating the role of LSVs and other pathogens on honey bee health at both the individual and colony levels. PMID:26110586

  17. Oral manifestations of hepatitis C virus infection

    PubMed Central

    Carrozzo, Marco; Scally, Kara

    2014-01-01

    Extrahepatic manifestations (EHMs) of hepatitis C virus (HCV) infection can affect a variety of organ systems with significant morbidity and mortality. Some of the most frequently reported EHM of HCV infection, involve the oral region predominantly or exclusively. Oral lichen planus (OLP) is a chronic inflammatory condition that is potentially malignant and represents cell-mediated reaction to a variety of extrinsic antigens, altered self-antigens, or super antigens. Robust epidemiological evidence support the link between OLP and HCV. As the virus may replicate in the oral mucosa and attract HCV-specific T lymphocytes, HCV may be implicated in OLP pathogenesis. Sjögren syndrome (SjS) is an autoimmune exocrinopathy, characterized by dryness of the mouth and eyes and a multitude of other systemic signs and symptoms. SjS patients have also an increased risk of non-Hodgkin lymphoma. Patients with chronic hepatitis C do frequently have histological signs of Sjögren-like sialadenitis with mild or even absent clinical symptoms. However, it is still unclear if HCV may cause a disease mimicking SjS or it is directly responsible for the development of SjS in a specific subset of patients. Oral squamous cell carcinoma is the most common oral malignant tumour and at least in some part of the world could be linked to HCV. PMID:24976694

  18. Encephalomyocarditis virus infections in an Australian zoo.

    PubMed

    Reddacliff, L A; Kirkland, P D; Hartley, W J; Reece, R L

    1997-06-01

    Fatal encephalomyocarditis virus (EMCV) infections in a ring-tailed lemur (Lemur catta), a squirrel monkey (Saimiri sciureus), three mandrills (Mandrillus sphinx), a chimpanzee (Pan troglodytes), a pygmy hippopotamus (Choeropsis liberiensis), and two Goodfellows tree kangaroos (Dendrolagus goodfellowi) occurred at Taronga Zoo. This is the first description of EMCV in a zoological collection outside of the United States. Regardless of species, the most common clinical presentation was sudden death. The gross pathologic changes were diffuse or focal pallor of the myocardium with occasional marked pulmonary congestion. Necrotizing nonsuppurative myocarditis was consistently present. EMCV was isolated from only one of 54 feral rodents examined. No antibodies to EMCV were detected with a serum neutralization test in 79 stored sera from a wide variety of zoo mammals. Titers of 1:16, 1:16, and 1:4 were recorded for a spider monkey (Aeteles geoffroyi), a lion (Panthera leo), and an orangutan (Pongo pygmaeus), respectively. Of seven mandrills tested in 1988, six had measurable virus titers. Later testing indicated that these titers did not persist, and one mandrill with a titer > 1:128 in 1988 subsequently succumbed to EMCV infection in 1991. PMID:9279403

  19. Influenza Activity - United States, 2015-16 Season and Composition of the 2016-17 Influenza Vaccine.

    PubMed

    Davlin, Stacy L; Blanton, Lenee; Kniss, Krista; Mustaquim, Desiree; Smith, Sophie; Kramer, Natalie; Cohen, Jessica; Cummings, Charisse Nitura; Garg, Shikha; Flannery, Brendan; Fry, Alicia M; Grohskopf, Lisa A; Bresee, Joseph; Wallis, Teresa; Sessions, Wendy; Garten, Rebecca; Xu, Xiyan; Elal, Anwar Isa Abd; Gubareva, Larisa; Barnes, John; Wentworth, David E; Burns, Erin; Katz, Jacqueline; Jernigan, Daniel; Brammer, Lynnette

    2016-01-01

    During the 2015-16 influenza season (October 4, 2015-May 21, 2016) in the United States, influenza activity* was lower and peaked later compared with the previous three seasons (2012-13, 2013-14, and 2014-15). Activity remained low from October 2015 until late December 2015 and peaked in mid-March 2016. During the most recent 18 influenza seasons (including this season), only two other seasons have peaked in March (2011-12 and 2005-06). Overall influenza activity was moderate this season, with a lower percentage of outpatient visits for influenza-like illness (ILI),(†) lower hospitalization rates, and a lower percentage of deaths attributed to pneumonia and influenza (P&I) compared with the preceding three seasons. Influenza A(H1N1)pdm09 viruses predominated overall, but influenza A(H3N2) viruses were more commonly identified from October to early December, and influenza B viruses were more commonly identified from mid-April through mid-May. The majority of viruses characterized this season were antigenically similar to the reference viruses representing the recommended components of the 2015-16 Northern Hemisphere influenza vaccine (1). This report summarizes influenza activity in the United States during the 2015-16 influenza season (October 4, 2015-May 21, 2016)(§) and reports the vaccine virus components recommended for the 2016-17 Northern Hemisphere influenza vaccines. PMID:27281364

  20. Rabies virus infects mouse and human lymphocytes and induces apoptosis.

    PubMed Central

    Thoulouze, M I; Lafage, M; Montano-Hirose, J A; Lafon, M

    1997-01-01

    Attenuated and highly neurovirulent rabies virus strains have distinct cellular tropisms. Highly neurovirulent strains such as the challenge virus standard (CVS) are highly neurotropic, whereas the attenuated strain ERA also infects nonneuronal cells. We report that both rabies virus strains infect activated murine lymphocytes and the human lymphoblastoid Jurkat T-cell line in vitro. The lymphocytes are more permissive to the attenuated ERA rabies virus strain than to the CVS strain in both cases. We also report that in contrast to that of the CVS strain, ERA viral replication induces apoptosis of infected Jurkat T cells, and cell death is concomitant with viral glycoprotein expression, suggesting that this protein has a role in the induction of apoptosis. Our data indicate that (i) rabies virus infects lymphocytes, (ii) lymphocyte infection with the attenuated rabies virus strain causes apoptosis, and (iii) apoptosis does not hinder rabies virus production. In contrast to CVS, ERA rabies virus and other attenuated rabies virus vaccines stimulate a strong immune response and are efficient live vaccines. The paradoxical finding that a rabies virus triggers a strong immune response despite the fact that it infects lymphocytes and induces apoptosis is discussed in terms of the function of apoptosis in the immune response. PMID:9311815

  1. Simultaneous multiplex PCR detection of seven cucurbit-infecting viruses.

    PubMed

    Kwon, Ji Yeon; Hong, Jin Sung; Kim, Min Jea; Choi, Sun Hee; Min, Byeong Eun; Song, Eun Gyeong; Kim, Hyun Hee; Ryu, Ki Hyun

    2014-09-01

    Two multiplex polymerase chain reaction (PCR) systems using dual priming oligonucleotide (DPO) primers were developed for the simultaneous detection of seven cucurbit-infecting viruses. One system allows for the detection of papaya ringspot virus, watermelon mosaic virus, and zucchini yellow mosaic virus, whereas the other permits the detection of cucumber green mottle mosaic virus, cucumber fruit mottle mosaic virus, kyuri green mottle mosaic virus, and zucchini green mottle mosaic virus. Viral species-specific DPO primers developed in this study detected as little as 10 fg/μl of viral RNA under monoplex conditions and 10 pg/μl of viral RNA under multiplex conditions. Multiplex PCR using the DPO primer sets was capable of amplifying viral genes at annealing temperatures ranging from 53 °C to 63 °C. Whereas the use of conventional primers gave rise to non-specific bands, the DPO primers detected target viral genes in the absence of non-specific amplification. When these DPO multiplex primer sets were applied to virus-infected cucurbit samples obtained in the field, multiple infection as well as single infection was accurately identified. This novel approach could also detect multiple viruses in infected seeds. The reliability of multiplex PCR systems using DPO primers for plant virus detection is discussed. PMID:24937806

  2. Human Muscle Satellite Cells as Targets of Chikungunya Virus Infection

    PubMed Central

    Ozden, Simona; Huerre, Michel; Riviere, Jean-Pierre; Coffey, Lark L.; Afonso, Philippe V.; Mouly, Vincent; de Monredon, Jean; Roger, Jean-Christophe; El Amrani, Mohamed; Yvin, Jean-Luc; Jaffar, Marie-Christine; Frenkiel, Marie-Pascale; Sourisseau, Marion; Schwartz, Olivier; Butler-Browne, Gillian; Desprès, Philippe; Gessain, Antoine; Ceccaldi, Pierre-Emmanuel

    2007-01-01

    Background Chikungunya (CHIK) virus is a mosquito-transmitted alphavirus that causes in humans an acute infection characterised by fever, polyarthralgia, head-ache, and myalgia. Since 2005, the emergence of CHIK virus was associated with an unprecedented magnitude outbreak of CHIK disease in the Indian Ocean. Clinically, this outbreak was characterized by invalidating poly-arthralgia, with myalgia being reported in 97.7% of cases. Since the cellular targets of CHIK virus in humans are unknown, we studied the pathogenic events and targets of CHIK infection in skeletal muscle. Methodology/Principal Findings Immunohistology on muscle biopsies from two CHIK virus-infected patients with myositic syndrome showed that viral antigens were found exclusively inside skeletal muscle progenitor cells (designed as satelllite cells), and not in muscle fibers. To evaluate the ability of CHIK virus to replicate in human satellite cells, we assessed virus infection on primary human muscle cells; viral growth was observed in CHIK virus-infected satellite cells with a cytopathic effect, whereas myotubes were essentially refractory to infection. Conclusions/Significance This report provides new insights into CHIK virus pathogenesis, since it is the first to identify a cellular target of CHIK virus in humans and to report a selective infection of muscle satellite cells by a viral agent in humans. PMID:17565380

  3. Pathogenesis and pathobiology of avian influenza virus infection in birds

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Avian Influenza (AI) viruses vary in their ability to produce infection, disease and death in different bird species. Based on the pathobiological features in chickens, AI viruses are categorized as, low (LP) and high pathogenicity (HP). Typically, LPAI (low pathogenicity avian influenza) viruses ...

  4. Pathobiology of avian influenza virus infections in wild birds

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Individual avian Influenza (AI) viruses vary in their ability to produce infection, disease and death in different bird species. Based on the pathobiological features in chickens, AI viruses (AIV) are categorized as low pathogenicity (LPAI) or high pathogenicity (HPAI) viruses, and can be of any of...

  5. Comparative pathology of select agent influenza A virus infections

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Influenza A virus infections may spread rapidly in human populations and cause acute respiratory disease with variable mortality. Two of these influenza viruses have been designated as select agents because of the high case fatality rate: 1918 H1N1 virus and highly pathogenic avian influenza (HPAI) ...

  6. Zika Virus Infection Acquired During Brief Travel to Indonesia

    PubMed Central

    Kwong, Jason C.; Druce, Julian D.; Leder, Karin

    2013-01-01

    Zika virus infection closely resembles dengue fever. It is possible that many cases are misdiagnosed or missed. We report a case of Zika virus infection in an Australian traveler who returned from Indonesia with fever and rash. Further case identification is required to determine the evolving epidemiology of this disease. PMID:23878182

  7. If You Have Chronic Hepatitis B Virus (HBV) Infection

    MedlinePlus

    If you have chronic hepatitis B virus (HBV) infection . . . If you have chronic hepatitis B virus (HBV) infection, you are not alone. Today, approximately one ... receive pneumococcal polysaccharide vac- cine.  Get vaccinated against hepatitis A. Hepati- tis A can further damage your ...

  8. First Imported Case of Zika Virus Infection into Korea.

    PubMed

    Jang, Hee-Chang; Park, Wan Beom; Kim, Uh Jin; Chun, June Young; Choi, Su-Jin; Choe, Pyoeng Gyun; Jung, Sook-In; Jee, Youngmee; Kim, Nam-Joong; Choi, Eun Hwa; Oh, Myoung-Don

    2016-07-01

    Since Zika virus has been spreading rapidly in the Americas from 2015, the outbreak of Zika virus infection becomes a global health emergency because it can cause neurological complications and adverse fetal outcome including microcephaly. Here, we report clinical manifestations and virus isolation findings from a case of Zika virus infection imported from Brazil. The patient, 43-year-old Korean man, developed fever, myalgia, eyeball pain, and maculopapular rash, but not neurological manifestations. Zika virus was isolated from his semen, and reverse-transcriptase PCR was positive for the virus in the blood, urine, and saliva on the 7th day of the illness but was negative on the 21st day. He recovered spontaneously without any neurological complications. He is the first case of Zika virus infection in Korea imported from Brazil. PMID:27366020

  9. First Imported Case of Zika Virus Infection into Korea

    PubMed Central

    Jee, Youngmee

    2016-01-01

    Since Zika virus has been spreading rapidly in the Americas from 2015, the outbreak of Zika virus infection becomes a global health emergency because it can cause neurological complications and adverse fetal outcome including microcephaly. Here, we report clinical manifestations and virus isolation findings from a case of Zika virus infection imported from Brazil. The patient, 43-year-old Korean man, developed fever, myalgia, eyeball pain, and maculopapular rash, but not neurological manifestations. Zika virus was isolated from his semen, and reverse-transcriptase PCR was positive for the virus in the blood, urine, and saliva on the 7th day of the illness but was negative on the 21st day. He recovered spontaneously without any neurological complications. He is the first case of Zika virus infection in Korea imported from Brazil. PMID:27366020

  10. Agglutination of Sindbis Virus and of Cells Infected with Sindbis Virus by Plant Lectins

    PubMed Central

    Birdwell, Charles R.; Strauss, James H.

    1973-01-01

    We have examined the agglutination of Sindbis virus and of chick and hamster cells infected with Sindbis virus by two of the plant lectins, concanavalin A and Ricinus communis agglutinin. Both lectins agglutinate the virus by binding to the polysaccharide chains of the envelope glycoproteins. Both chick and hamster cells exhibit increased agglutination by the lectins after infection by Sindbis virus. In the case of chick cells infected with Sindbis virus, this increase in agglutinability occurs between 3 and 5 h after infection. Infected and mock-infected cells bind the same amount of 3H-labeled concanavalin A, which suggests that the increase in agglutination after infection is due to rearrangements at the cell surface rather than to insertion of new lectin binding sites per se. PMID:4735591

  11. Identification of a Role for Nucleolin in Rabies Virus Infection

    PubMed Central

    Oksayan, S.; Nikolic, J.; David, C. T.; Blondel, D.; Jans, D. A.

    2014-01-01

    Rabies virus replicates in the cytoplasm of host cells, but rabies virus phosphoprotein (P-protein) undergoes active nucleocytoplasmic trafficking. Here we show that the largely nuclear P-protein isoform P3 can localize to nucleoli and forms specific interactions with nucleolin. Importantly, depletion of nucleolin expression inhibits viral protein expression and infectious virus production by infected cells. This provides the first evidence that lyssaviruses interact with nucleolin and that nucleolin is important to lyssavirus infection. PMID:25428867

  12. Identification of a role for nucleolin in rabies virus infection.

    PubMed

    Oksayan, S; Nikolic, J; David, C T; Blondel, D; Jans, D A; Moseley, G W

    2015-02-01

    Rabies virus replicates in the cytoplasm of host cells, but rabies virus phosphoprotein (P-protein) undergoes active nucleocytoplasmic trafficking. Here we show that the largely nuclear P-protein isoform P3 can localize to nucleoli and forms specific interactions with nucleolin. Importantly, depletion of nucleolin expression inhibits viral protein expression and infectious virus production by infected cells. This provides the first evidence that lyssaviruses interact with nucleolin and that nucleolin is important to lyssavirus infection. PMID:25428867

  13. Pathogenesis of Hendra and Nipah virus infection in humans.

    PubMed

    Escaffre, Olivier; Borisevich, Viktoriya; Rockx, Barry

    2013-04-01

    Hendra virus (HeV) and Nipah virus (NiV) are emerging zoonotic viruses that cause severe and often lethal respiratory illness and encephalitis in humans. Henipaviruses can infect a wide range of species and human-to-human transmission has been observed for NiV. While the exact route of transmission in humans is not known, experimental infection in different animal species suggests that infection can be efficiently initiated after respiratory challenge. The limited data on histopathological changes in fatal human cases of HeV and NiV suggest that endothelial cells are an important target during the terminal stage of infection; however, it is unknown where these viruses initially establish infection and how the virus disseminates from the respiratory tract to the central nervous system and other organs. Here we review the current concepts in henipavirus pathogenesis in humans. PMID:23592639

  14. Prevalence of occult hepatitis C virus infection in the Iranian patients with human immunodeficiency virus infection.

    PubMed

    Bokharaei-Salim, Farah; Keyvani, Hossein; Esghaei, Maryam; Zare-Karizi, Shohreh; Dermenaki-Farahani, Sahar-Sadat; Hesami-Zadeh, Khashayar; Fakhim, Shahin

    2016-11-01

    Occult hepatitis C virus (HCV) infection is a new form of chronic HCV infection described by the presence of the genomic HCV-RNA in liver biopsy and/or peripheral blood mononuclear cell (PBMC) samples, and undetectable levels or absence of HCV-RNA and in the absence or presence of anti HCV antibodies in the plasma specimens. The aim of the present study was to evaluate the occurrence of occult HCV infection (OCI) among Iranian subjects infected with human immunodeficiency virus (HIV) using RT-nested PCR. From March 2014 until April 2015, 109 Iranian patients with established HIV infection were enrolled in this cross-sectional study. After extraction of viral RNA from the plasma and PBMC samples, HCV-RNA status was examined by RT-nested PCR using primers from the 5'-NTR. HCV genotyping was conducted using RFLP analysis. For the confirmation of HCV genotyping by RFLP method, the PCR products were sequenced. Of the 109 patients, 50 were positive for antibodies against HCV. The HCV-RNA was detected in PBMC specimens in 6 (10.2%) out of the total 59 patients negative for anti-HCV Abs and undetectable plasma HCV-RNA and also from 4 (8.0%) out of the total 50 patients positive for anti-HCV Abs and undetectable plasma HCV-RNA. HCV genotyping analysis showed that 6 (60.0%) patients were infected with HCV subtype 3a, 3 (30.0%) were infected with HCV subtype 1a and 1 (10.0%) patient was infected with HCV subtype 1b. This study revealed the incidence of OCI (9.2%) in HIV-infected Iranian patients. Hence, designing prospective studies focusing on the detection of OCI in these patients would provide more information. J. Med. Virol. 88:1960-1966, 2016. © 2016 Wiley Periodicals, Inc. PMID:27463051

  15. Bovine respiratory disease model based on dual infections with infection with bovine viral diarrhea virus and bovine corona virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine respiratory disease complex (BRDC) is the leading cause of economic loss in the U.S. cattle industry. BRDC likely results from simultaneous or sequential infections with multiple pathogens including both viruses and bacteria. Bovine viral diarrhea virus (BVDV) and bovine corona virus (BoCV...

  16. Respiratory Syncytial Virus Infection in Adults

    PubMed Central

    Falsey, Ann R.; Walsh, Edward E.

    2000-01-01

    Respiratory syncytial virus (RSV) is now recognized as a significant problem in certain adult populations. These include the elderly, persons with cardiopulmonary diseases, and immunocompromised hosts. Epidemiological evidence indicates that the impact of RSV in older adults may be similar to that of nonpandemic influenza. In addition, RSV has been found to cause 2 to 5% of adult community-acquired pneumonias. Attack rates in nursing homes are approximately 5 to 10% per year, with significant rates of pneumonia (10 to 20%) and death (2 to 5%). Clinical features may be difficult to distinguish from those of influenza but include nasal congestion, cough, wheezing, and low-grade fever. Bone marrow transplant patients prior to marrow engraftment are at highest risk for pneumonia and death. Diagnosis of RSV infection in adults is difficult because viral culture and antigen detection are insensitive, presumably due to low viral titers in nasal secretions, but early bronchoscopy is valuable in immunosuppressed patients. Treatment of RSV in the elderly is largely supportive, whereas early therapy with ribavirin and intravenous gamma globulin is associated with improved survival in immunocompromised persons. An effective RSV vaccine has not yet been developed, and thus prevention of RSV infection is limited to standard infection control practices such as hand washing and the use of gowns and gloves. PMID:10885982

  17. Hepatitis B virus infection and intrahepatic cholangiocarcinoma

    PubMed Central

    Zhou, Hua-Bang; Hu, Jing-Yi; Hu, He-Ping

    2014-01-01

    Intrahepatic cholangiocarcinoma (ICC) is a devastating malignant tumor arising from the peripheral intrahepatic bile duct epithelium. The incidence and mortality of ICC is markedly increasing over the past two decades worldwide, though the cause for this rise in incidence is unclear, thus intensifying the search for alternative etiological agents and pathogenetic mechanisms. Hepatolithiasis, primary sclerosing cholangitis, parasitic infection (Opisthorchis viverrini or Clonorchis sinensis), fibropolycystic liver disease, and chemical carcinogen exposure are thought to be the risk factors for ICC. Nevertheless, the majority of ICC patients do not have any of these risk factors, and none of the established risk factors can explain the recent increasing trend of ICC. Therefore, identifying other risk factors may lead to the prevention and early detection of ICC. Chronic hepatitis B virus (HBV) infection is the predominant cause of hepatocellular carcinoma in HBV-endemic areas. This review discusses the evidence implicating chronic HBV infection as a likely etiology of ICC and the pathogenetic mechanisms that might be involved. PMID:24914333

  18. Epidemiological and Virological Characterization of Influenza B Virus Infections.

    PubMed

    Sharabi, Sivan; Drori, Yaron; Micheli, Michal; Friedman, Nehemya; Orzitzer, Sara; Bassal, Ravit; Glatman-Freedman, Aharona; Shohat, Tamar; Mendelson, Ella; Hindiyeh, Musa; Mandelboim, Michal

    2016-01-01

    While influenza A viruses comprise a heterogeneous group of clinically relevant influenza viruses, influenza B viruses form a more homogeneous cluster, divided mainly into two lineages: Victoria and Yamagata. This divergence has complicated seasonal influenza vaccine design, which traditionally contained two seasonal influenza A virus strains and one influenza B virus strain. We examined the distribution of the two influenza B virus lineages in Israel, between 2011-2014, in hospitalized and in non-hospitalized (community) influenza B virus-infected patients. We showed that influenza B virus infections can lead to hospitalization and demonstrated that during some winter seasons, both influenza B virus lineages circulated simultaneously in Israel. We further show that the influenza B virus Yamagata lineage was dominant, circulating in the county in the last few years of the study period, consistent with the anti-Yamagata influenza B virus antibodies detected in the serum samples of affected individuals residing in Israel in the year 2014. Interestingly, we found that elderly people were particularly vulnerable to Yamagata lineage influenza B virus infections. PMID:27533045

  19. Epidemiological and Virological Characterization of Influenza B Virus Infections

    PubMed Central

    Sharabi, Sivan; Drori, Yaron; Micheli, Michal; Friedman, Nehemya; Orzitzer, Sara; Bassal, Ravit; Glatman-Freedman, Aharona; Shohat, Tamar; Mendelson, Ella; Hindiyeh, Musa; Mandelboim, Michal

    2016-01-01

    While influenza A viruses comprise a heterogeneous group of clinically relevant influenza viruses, influenza B viruses form a more homogeneous cluster, divided mainly into two lineages: Victoria and Yamagata. This divergence has complicated seasonal influenza vaccine design, which traditionally contained two seasonal influenza A virus strains and one influenza B virus strain. We examined the distribution of the two influenza B virus lineages in Israel, between 2011–2014, in hospitalized and in non-hospitalized (community) influenza B virus-infected patients. We showed that influenza B virus infections can lead to hospitalization and demonstrated that during some winter seasons, both influenza B virus lineages circulated simultaneously in Israel. We further show that the influenza B virus Yamagata lineage was dominant, circulating in the county in the last few years of the study period, consistent with the anti-Yamagata influenza B virus antibodies detected in the serum samples of affected individuals residing in Israel in the year 2014. Interestingly, we found that elderly people were particularly vulnerable to Yamagata lineage influenza B virus infections. PMID:27533045

  20. Transcriptional Profiling of the Immune Response to Marburg Virus Infection

    PubMed Central

    Yen, Judy; Caballero, Ignacio S.; Garamszegi, Sara; Malhotra, Shikha; Lin, Kenny; Hensley, Lisa; Goff, Arthur J.

    2015-01-01

    ABSTRACT Marburg virus is a genetically simple RNA virus that causes a severe hemorrhagic fever in humans and nonhuman primates. The mechanism of pathogenesis of the infection is not well understood, but it is well accepted that pathogenesis is appreciably driven by a hyperactive immune response. To better understand the overall response to Marburg virus challenge, we undertook a transcriptomic analysis of immune cells circulating in the blood following aerosol exposure of rhesus macaques to a lethal dose of Marburg virus. Using two-color microarrays, we analyzed the transcriptomes of peripheral blood mononuclear cells that were collected throughout the course of infection from 1 to 9 days postexposure, representing the full course of the infection. The response followed a 3-stage induction (early infection, 1 to 3 days postexposure; midinfection, 5 days postexposure; late infection, 7 to 9 days postexposure) that was led by a robust innate immune response. The host response to aerosolized Marburg virus was evident at 1 day postexposure. Analysis of cytokine transcripts that were overexpressed during infection indicated that previously unanalyzed cytokines are likely induced in response to exposure to Marburg virus and further suggested that the early immune response is skewed toward a Th2 response that would hamper the development of an effective antiviral immune response early in disease. Late infection events included the upregulation of coagulation-associated factors. These findings demonstrate very early host responses to Marburg virus infection and provide a rich data set for identification of factors expressed throughout the course of infection that can be investigated as markers of infection and targets for therapy. IMPORTANCE Marburg virus causes a severe infection that is associated with high mortality and hemorrhage. The disease is associated with an immune response that contributes to the lethality of the disease. In this study, we investigated how the

  1. Sofosbuvir treatment and hepatitis C virus infection.

    PubMed

    Nakamura, Masato; Kanda, Tatsuo; Haga, Yuki; Sasaki, Reina; Wu, Shuang; Nakamoto, Shingo; Yasui, Shin; Arai, Makoto; Imazeki, Fumio; Yokosuka, Osamu

    2016-01-28

    Hepatitis C virus (HCV) infection is a serious problem worldwide. The use of interferon-based therapy has made HCV eradication challenging. The recent appearance of direct-acting antiviral agents (DAAs) has changed HCV therapy. Combining the use of DAAs with peginterferon and ribavirin has improved treatment efficacy. Furthermore, the combination of different orally administered DAAs has enabled interferon-free therapy with much higher efficacy and safety. In particular, sofosbuvir, a nucleotide-based NS5B inhibitor, prevents HCV RNA synthesis by acting as a "chain terminator". Treatment with sofosbuvir has attained an extremely high rate of sustained virologic response. The current review summarizes the efficacy and safety of sofosbuvir therapy. PMID:26839641

  2. Sofosbuvir treatment and hepatitis C virus infection

    PubMed Central

    Nakamura, Masato; Kanda, Tatsuo; Haga, Yuki; Sasaki, Reina; Wu, Shuang; Nakamoto, Shingo; Yasui, Shin; Arai, Makoto; Imazeki, Fumio; Yokosuka, Osamu

    2016-01-01

    Hepatitis C virus (HCV) infection is a serious problem worldwide. The use of interferon-based therapy has made HCV eradication challenging. The recent appearance of direct-acting antiviral agents (DAAs) has changed HCV therapy. Combining the use of DAAs with peginterferon and ribavirin has improved treatment efficacy. Furthermore, the combination of different orally administered DAAs has enabled interferon-free therapy with much higher efficacy and safety. In particular, sofosbuvir, a nucleotide-based NS5B inhibitor, prevents HCV RNA synthesis by acting as a “chain terminator”. Treatment with sofosbuvir has attained an extremely high rate of sustained virologic response. The current review summarizes the efficacy and safety of sofosbuvir therapy. PMID:26839641

  3. Glucose abnormalities in hepatitis C virus infection.

    PubMed

    Huang, Jee-Fu; Yu, Ming-Lung; Dai, Chia-Yen; Chuang, Wan-Long

    2013-02-01

    Hepatitis C virus (HCV) infection is one of the most important causes of cirrhosis and hepatocellular carcinoma and has a tremendous impact on public health worldwide. HCV is both hepatotropic and lymphotropic. Replication of HCV in diseased extrahepatic organs and tissues may either trigger latent autoimmunity or induce autoimmune disorders. In addition to established liver injury, type 2 diabetes mellitus (T2DM) is an important feature of extrahepatic metabolic disorders which is attributed to HCV infection. It also has some impact on the disease activity, disease course, clinical outcomes, and treatment efficacy of antiviral therapy. Previous experimental and clinical findings have highly suggested that HCV per se is diabetogenic. The cause-effect interaction between a common endocrine disorder and an infectious disease is an important issue to elucidate. Although the precise mechanisms whereby HCV infection leads to insulin resistance (IR) and glucose abnormalities are not entirely clear, it differs from the usual pathogenesis of T2DM in those with non-HCV liver diseases. This review initially highlights epidemiological and pathophysiological studies addressing the mutual link between chronic HCV infection (CHC) and T2DM. The characteristics of glucose abnormalities in this special population are depicted from the current evidence. The mutual roles of IR and CHC with respect to the prediction of treatment efficacy, how treatment response affects IR, and the role of pancreatic beta cell function in the entire suite are discussed. With the rapid progression of antiviral therapy for CHC in the past decade, we have also listed some points of future perspective in this issue. PMID:23347806

  4. Susceptibility of mouse macrophage J774 to dengue virus infection.

    PubMed

    Moreno-Altamirano, María M B; Sánchez-García, F Javier; Legorreta-Herrera, Martha; Aguilar-Carmona, Israel

    2007-01-01

    The aim of this study was to investigate whether the J774 mouse macrophage cell line could be used as an in vitro model for dengue virus infection (DENV). After 3 days, infection in J774 cells was assessed by detecting dengue virus non-structural protein 1 (NSP-1) production either by dot blot or indirect immunofluorescence assay (IFA) of saponine-permeabilized J774 cells and then confirmed by RT-PCR (171 bp product, corresponding to the DENV-2 core). Based on the presence of NSP-1 in infected but not in non-infected cells by both IFA and dot blot, as well as the amplification of a 171-bp DENV-2-specific RT-PCR product exclusively in the infected cells, the J774 cell line was found to be permissive for dengue virus infection. As far as we know, this is the first report that the J774 mouse macrophage cell line is infected with dengue virus and, thus, that it can be used as an alternative in vitro model for dengue virus infection studies. This finding could help to further elucidate the mechanisms involved in dengue virus infection and pathogenesis. PMID:17356302

  5. Unfolded protein response in hepatitis C virus infection

    PubMed Central

    Chan, Shiu-Wan

    2014-01-01

    Hepatitis C virus (HCV) is a single-stranded, positive-sense RNA virus of clinical importance. The virus establishes a chronic infection and can progress from chronic hepatitis, steatosis to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). The mechanisms of viral persistence and pathogenesis are poorly understood. Recently the unfolded protein response (UPR), a cellular homeostatic response to endoplasmic reticulum (ER) stress, has emerged to be a major contributing factor in many human diseases. It is also evident that viruses interact with the host UPR in many different ways and the outcome could be pro-viral, anti-viral or pathogenic, depending on the particular type of infection. Here we present evidence for the elicitation of chronic ER stress in HCV infection. We analyze the UPR signaling pathways involved in HCV infection, the various levels of UPR regulation by different viral proteins and finally, we propose several mechanisms by which the virus provokes the UPR. PMID:24904547

  6. Antibody dependent enhancement of frog virus 3 infection

    PubMed Central

    2010-01-01

    Background Viruses included in the family Iridoviridae are large, icosahedral, dsDNA viruses that are subdivided into 5 genera. Frog virus 3 (FV3) is the type species of the genus Ranavirus and the best studied iridovirus at the molecular level. Typically, antibodies directed against a virus act to neutralize the virus and limit infection. Antibody dependent enhancement occurs when viral antibodies enhance infectivity of the virus rather than neutralize it. Results Here we show that anti-FV3 serum present at the time of FV3 infection enhances infectivity of the virus in two non-immune teleost cell lines. We found that antibody dependent enhancement of FV3 was dependent on the Fc portion of anti-FV3 antibodies but not related to complement. Furthermore, the presence of anti-FV3 serum during an FV3 infection in a non-immune mammalian cell line resulted in neutralization of the virus. Our results suggest that a cell surface receptor specific to teleost cell lines is responsible for the enhancement. Conclusions This report represents the first evidence of antibody dependent enhancement in iridoviruses. The data suggests that anti-FV3 serum can either neutralize or enhance viral infection and that enhancement is related to a novel antibody dependent enhancement pathway found in teleosts that is Fc dependent. PMID:20167100

  7. Hepatitis E virus infection in the HIV-positive patient.

    PubMed

    Debes, Jose D; Pisano, Maria Belen; Lotto, Martin; Re, Viviana

    2016-07-01

    Hepatitis E virus (HEV) is a RNA virus that can cause hepatitis. In immunocompetent individuals, infection with HEV usually leads to asymptomatic seroconversion. However, in immunosuppressed patients, such as transplant recipients, HEV can develop into a chronic infection. Studies regarding the seroprevalence and clinical implications of HEV in patients infected with the human immunodeficiency virus (HIV) are conflicting. Levels of CD4 count in blood seem to be the most widely associated risk factor, while other factors such as meat consumption or proximity to animals are less clearly associated with HEV infection. Progression to chronicity, as well as extrahepatic manifestations of HEV seem rare in HIV, and the implications of HEV in liver disease progression are poorly understood in the HIV-infected. In this review we describe the epidemiology, risk factors, and clinical implications of HEV infection in individuals infected with HIV. PMID:27243210

  8. Analysis of in vivo dynamics of influenza virus infection in mice using a GFP reporter virus

    PubMed Central

    Manicassamy, Balaji; Manicassamy, Santhakumar; Belicha-Villanueva, Alan; Pisanelli, Giuseppe; Pulendran, Bali; García-Sastre, Adolfo

    2010-01-01

    Influenza A virus is being extensively studied because of its major impact on human and animal health. However, the dynamics of influenza virus infection and the cell types infected in vivo are poorly understood. These characteristics are challenging to determine, partly because there is no efficient replication-competent virus expressing an easily traceable reporter gene. Here, we report the generation of a recombinant influenza virus carrying a GFP reporter gene in the NS segment (NS1-GFP virus). Although attenuated when compared with wild-type virus, the NS1-GFP virus replicates efficiently in murine lungs and shows pathogenicity in mice. Using whole-organ imaging and flow cytometry, we have tracked the dynamics of influenza virus infection progression in mice. Imaging of murine lungs shows that infection starts in the respiratory tract in areas close to large conducting airways and later spreads to deeper sections of the lungs. In addition to epithelial cells, we found GFP-positive antigen-presenting cells, such as CD11b+CD11c−, CD11b−CD11c+, and CD11b+CD11c+, as early as 24 h after intranasal infection. In addition, a significant proportion of NK and B cells were GFP positive, suggesting active infection of these cells. We next tested the effects of the influenza virus inhibitors oseltamivir and amantadine on the kinetics of in vivo infection progression. Treatment with oseltamivir dramatically reduced influenza infection in all cell types, whereas, surprisingly, amantadine treatment more efficiently blocked infection in B and NK cells. Our results demonstrate high levels of immune cells harboring influenza virus antigen during viral infection and cell-type–specific effects upon treatment with antiviral agents, opening additional avenues of research in the influenza virus field. PMID:20534532

  9. Absence of Active Hepatitis C Virus Infection in Human Immunodeficiency Virus Clinics in Zambia and Mozambique

    PubMed Central

    Wandeler, Gilles; Mulenga, Lloyd; Hobbins, Michael; Joao, Candido; Sinkala, Edford; Hector, Jonas; Aly, Musa; Chi, Benjamin H.; Egger, Matthias; Vinikoor, Michael J.

    2016-01-01

    Few studies have evaluated the prevalence of replicating hepatitis C virus (HCV) infection in sub-Saharan Africa. Among 1812 individuals infected with human immunodeficiency virus, no patient in rural Mozambique and 4 patients in urban Zambia were positive for anti-HCV antibodies. Of these, none had confirmed HCV replication. PMID:27047986

  10. Hemophagocytic lymphohistiocytosis associated with SFTS virus infection

    PubMed Central

    Oh, Hong Sang; Kim, Moonsuk; Lee, Jeong-Ok; Kim, Haeryoung; Kim, Eu Suk; Park, Kyoung Un; Kim, Hong Bin; Song, Kyoung-Ho

    2016-01-01

    Abstract Background: Severe fever with thrombocytopenia syndrome (SFTS) is a new emerging zoonosis. Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome caused by hyperinflammation. Here, we report the case of SFTS-associated HLH. Case summary: A 62-year-old man was admitted to local hospital with 8 days of fever and chill. He had leukopenia, thrombocytopenia, and developed seizure. An attending physician examined bone marrow to rule out hematologic malignancy. He was transferred to tertiary referral hospital for suspicious HLH. We decided to confirm its histologic feature for sure. Bone marrow and liver biopsy showed hemophagocyotic histiocytes. Serological tests for other infections were all negative except SFTS virus polymerase chain reactions (PCRs) as positive from serum, bone marrow, bronchoalveolar lavage fluid, and liver biopsy specimen. A definitive diagnosis was SFTS-associated HLH. During 2 weeks of conservative treatment, he succeeded in recovery from multiple organ failure. Conclusion: SFTS should be considered one of differential diagnosis of HLH. In certain endemic areas, SFTS infection deserves clinicians’ attention because it can be presented hematologic diseases as HLH. PMID:27495089

  11. Development of vaccines for prevention of Ebola virus infection.

    PubMed

    Ye, Ling; Yang, Chinglai

    2015-02-01

    Ebola virus infection causes severe hemorrhagic fevers with high fatality rates up to 90% in humans, for which no effective treatment is currently available. The ongoing Ebola outbreak in West Africa that has caused over 14,000 human infections and over 5000 deaths underscores its serious threat to the public health. While licensed vaccines against Ebola virus infection are still not available, a number of vaccine approaches have been developed and shown to protect against lethal Ebola virus infection in animal models. This review aims to summarize the advancement of different strategies for Ebola vaccine development with a focus on the discussion of their protective efficacies and possible limitations. In addition, the development of animal models for efficacy evaluation of Ebola vaccines and the mechanism of immune protection against Ebola virus infection are also discussed. PMID:25526819

  12. Nontyphoidal Salmonellosis, Human Immunodeficiency Virus Infection, and Ischemic Stroke

    PubMed Central

    Piggott, Damani A.; Carroll, Karen C.; Lim, Michael; Melia, Michael T.

    2016-01-01

    Nontyphoidal Salmonella infection and stroke are major causes of morbidity and mortality worldwide, with increased risk in the human immunodeficiency virus (HIV)-infected population. We report a rare case of ischemic stroke associated with Salmonella enteritidis subdural empyema in an older HIV-infected patient with multimorbidity, despite surgery and treatment with susceptible antimicrobial drugs. PMID:27419176

  13. Nontyphoidal Salmonellosis, Human Immunodeficiency Virus Infection, and Ischemic Stroke.

    PubMed

    Piggott, Damani A; Carroll, Karen C; Lim, Michael; Melia, Michael T

    2016-04-01

    Nontyphoidal Salmonella infection and stroke are major causes of morbidity and mortality worldwide, with increased risk in the human immunodeficiency virus (HIV)-infected population. We report a rare case of ischemic stroke associated with Salmonella enteritidis subdural empyema in an older HIV-infected patient with multimorbidity, despite surgery and treatment with susceptible antimicrobial drugs. PMID:27419176

  14. Influenza Illness in Pregnant Indian Women: A Cross-Sectional Study

    PubMed Central

    Koul, Parvaiz A.; Bali, Nargis K.; Mir, Hyder; Jabeen, Farhat; Ahmad, Abida

    2016-01-01

    Data about burden of influenza in pregnancy in India are scant. In order to assess the contribution of influenza to acute respiratory illness (ARI) in pregnancy, 266 north Indian pregnant females with febrile ARI were studied from December 2014 to May 2015. Twin nasopharyngeal/oropharyngeal swabs were obtained and tested for influenza viruses by RT-PCR. Fifty (18.8%) patients tested positive for influenza (A/H1N1pdm09 in 41, A/H3N2 in 8, and influenza B Yamagata in 1). Rigors, headache, and a family history of ARI were significantly more frequent in influenza positive patients. Oseltamivir and supportive therapy were administered to all confirmed cases. Nine influenza positive cases needed hospitalization for their respiratory illness, and 5 developed respiratory failure. Of these, 4 (3 in third trimester) succumbed to their illness. We conclude that influenza viruses are a cause of significant morbidity and mortality among pregnant females with ARI in north India. As such, appropriate preventive strategies of influenza vaccination and early initiation of antiviral therapy during illness are stressed. PMID:26903762

  15. Role of oxidative stress in rabies virus infection.

    PubMed

    Jackson, Alan C; Kammouni, Wafa; Fernyhough, Paul

    2011-01-01

    Recent studies in an experimental model of rabies indicated that there are major structural changes in the brain involving neuronal processes that are associated with severe clinical disease. Cultured adult mouse dorsal root ganglion (DRG) neurons are a good in vitro model for studying the mechanisms involved in rabies virus-induced degeneration of neurites (axons) because, unlike other neuronal cell types, these neurons are fairly permissive to rabies virus infection. DRG neurons infected with the challenge virus standard-11 (CVS) strain of rabies virus show axonal swellings and immunostaining for 4-hydroxy-2-nonenal (4-HNE), indicating evidence of lipid peroxidation associated with oxidative stress, and also reduced axonal growth in comparison with mock-infected DRG neurons. Treatment with the antioxidant N-acetyl cysteine prevented the reduction in axonal outgrowth that occurred with CVS infection. The axonal swellings with 4-HNE-labeled puncta were found to be associated with aggregations of actively respiring mitochondria. We postulate that rabies virus infection likely induces mitochondrial dysfunction resulting in oxidative stress and degenerative changes involving neuronal processes. This mitochondrial dysfunction may be the result of either direct or indirect effects of the virus on the mitochondrial electron-transport chain or it may occur through other mechanisms. Further investigations are needed to gain a better understanding of the basic mechanisms involved in the oxidative damage associated with rabies virus infection. This information may prove helpful in the design of future therapeutic effects for this dreaded ancient disease. PMID:21601046

  16. Prevalence of Hepatitis Virus Infections in an Institution for Persons with Developmental Disabilities.

    ERIC Educational Resources Information Center

    Woodruff, Bradley A.; Vazquez, Elizabeth

    2002-01-01

    A study involving 1,235 residents of Sonoma Developmental Center found 3 residents had hepatitis C virus infections, and 633 had past or current hepatitis B virus infections. The prevalence of hepatitis B virus infection rose rapidly with longer residence in institutions. Hepatitis A virus infection had occurred in 494 residents. (Contains…

  17. Border disease in sheep caused by transmission of virus from cattle persistently infected with bovine virus diarrhoea virus.

    PubMed

    Carlsson, U

    1991-02-16

    Two outbreaks of border disease occurred on farms with sheep flocks and breeding cattle. The infection of the pregnant sheep was probably caused by transmission of virus from calves persistently infected with non-cytopathic bovine virus diarrhoea virus (BVDV) which were kept in close confinement with the ewes during mid-pregnancy. Border disease was also induced experimentally in eight lambs by exposing their dams at 38 to 78 days of gestation to a heifer persistently infected with BVDV. Both the natural and the experimental infections were characterised by typical signs such as 'hairy-shaker' lambs and high lamb mortality. The diagnosis was confirmed by virus isolations from live-born lambs, seroconversion and pathology. The study supports the assertion that cattle persistently infected with BVDV and in close contact with pregnant sheep, are an important source of strains of virus capable of causing border disease. PMID:1851350

  18. 78 FR 33848 - Draft Guidance for Industry on Human Immunodeficiency Virus-1 Infection: Developing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-05

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry on Human Immunodeficiency Virus... availability of a draft guidance for industry entitled ``Human Immunodeficiency Virus-1 Infection: Developing... guidance for industry entitled ``Human Immunodeficiency Virus-1 Infection: Developing Antiretroviral...

  19. Modeling multiple infection of cells by viruses: challenges and insights

    PubMed Central

    Phan, Dustin; Wodarz, Dominik

    2015-01-01

    The multiple infection of cells with several copies of a given virus has been demonstrated in experimental systems, and has been subject to previous mathematical modeling approaches. Such models, especially those based on ordinary differential equations, can be characterized by difficulties and pitfalls. One such difficulty arises from what we refer to as multiple infection cascades. That is, such models subdivide the infected cell population into sub-populations that are carry i viruses, and each sub-population can in principle always be further infected to contain i+1 viruses. In order to study the model with numerical simulations, the infection cascade needs to be cut artificially, and this can influence the results. This is shown here in the context of the simplest setting that involves a single, homogeneous virus population. If the viral replication rate is sufficiently fast, then most infected cells will accumulate in the last member of the infection cascade, leading to incorrect numerical results. This can be observed even with relatively long infection cascades, and in this case computational costs associated with a sufficiently long infection cascade can render this approach impractical. We subsequently examine a more complex scenario where two virus types / strains with different fitness are allowed to compete. Again, we find that the length of the infection cascade can have a crucial influence on the results. Competitive exclusion can be observed for shorter infection cascades, while coexistence can be observed for longer infection cascades. More subtly, the length of the infection cascade can influence the equilibrium level of the populations in numerical simulations. Studying the model in a parameter regime where an increase in the infection cascade length does not influence the results, we examine the effect of multiple infection on the outcome of competition. We find that multiple infection can promote coexistence of virus types if there is a degree

  20. Zika virus productively infects primary human placenta-specific macrophages

    PubMed Central

    Jurado, Kellie Ann; Simoni, Michael K.; Tang, Zhonghua; Uraki, Ryuta; Hwang, Jesse; Householder, Sarah; Wu, Mingjie; Lindenbach, Brett D.; Abrahams, Vikki M.; Guller, Seth; Fikrig, Erol

    2016-01-01

    The strong association of Zika virus infection with congenital defects has led to questions of how a flavivirus is capable of crossing the placental barrier to reach the fetal brain. Here, we demonstrate permissive Zika virus infection of primary human placental macrophages, commonly referred to as Hofbauer cells, and placental villous fibroblasts. We also demonstrate Zika virus infection of Hofbauer cells within the context of the tissue ex vivo using term placental villous explants. In addition to amplifying infectious virus within a usually inaccessible area, the putative migratory activities of Hofbauer cells may aid in dissemination of Zika virus to the fetal brain. Understanding the susceptibility of placenta-specific cell types will aid future work around and understanding of Zika virus–associated pregnancy complications. PMID:27595140

  1. Immune responses of infants to infection with respiratory viruses and live attenuated respiratory virus candidate vaccines.

    PubMed

    Crowe, J E

    1998-01-01

    Respiratory viruses such as respiratory syncytial virus (RSV), the parainfluenza viruses (PIV), and the influenza viruses cause severe lower respiratory tract diseases in infants and children throughout the world. Experimental live attenuated vaccines for each of these viruses are being developed for intranasal administration in the first weeks or months of life. A variety of promising RSV, PIV-3, and influenza virus vaccine strains have been developed by classical biological methods, evaluated extensively in preclinical and clinical studies, and shown to be attenuated and genetically stable. The ongoing clinical evaluation of these vaccine candidates, coupled with recent major advances in the ability to develop genetically engineered viruses with specified mutations, may allow the rapid development of respiratory virus strains that possess ideal levels of replicative capacity and genetic stability in vivo. A major remaining obstacle to successful immunization of infants against respiratory virus associated disease may be the relatively poor immune response of very young infants to primary virus infection. This paper reviews the immune correlates of protection against disease caused by these viruses, immune responses of infants to naturally-acquired infection, and immune responses of infants to experimental infection with candidate vaccine viruses. PMID:9711783

  2. Edible bird's nest extract inhibits influenza virus infection.

    PubMed

    Guo, Chao-Tan; Takahashi, Tadanobu; Bukawa, Wakoto; Takahashi, Noriko; Yagi, Hirokazu; Kato, Koichi; Hidari, Kazuya I-P Jwa; Miyamoto, Daisei; Suzuki, Takashi; Suzuki, Yasuo

    2006-07-01

    Edible bird's nest (EBN) is the nest of the swift that is made from its saliva. Although EBN has been widely used for enhancing immunocompetence, its antiviral efficacy has not been studied in detail. We found that EBN extract could strongly inhibit infection with influenza viruses in a host range-independent manner when it was hydrolyzed with Pancreatin F. Western blotting assay showed that the EBN extract bound to influenza virus. Furthermore, EBN extract could neutralize the infection of MDCK cells with influenza viruses and inhibit hemagglutination of influenza viruses to erythrocytes, but it could not inhibit the activity of influenza virus sialidase. Fluorometric HPLC indicated that the major molecular species of sialic acid in EBN is N-acetylneuraminic acid. The results suggest that EBN is a safe and valid natural source for the prevention of influenza viruses. PMID:16581142

  3. The Impact of Wolbachia on Virus Infection in Mosquitoes

    PubMed Central

    Johnson, Karyn N.

    2015-01-01

    Mosquito-borne viruses such as dengue, West Nile and chikungunya viruses cause significant morbidity and mortality in human populations. Since current methods are not sufficient to control disease occurrence, novel methods to control transmission of arboviruses would be beneficial. Recent studies have shown that virus infection and transmission in insects can be impeded by co-infection with the bacterium Wolbachia pipientis. Wolbachia is a maternally inherited endosymbiont that is commonly found in insects, including a number of mosquito vector species. In Drosophila, Wolbachia mediates antiviral protection against a broad range of RNA viruses. This discovery pointed to a potential strategy to interfere with mosquito transmission of arboviruses by artificially infecting mosquitoes with Wolbachia. This review outlines research on the prevalence of Wolbachia in mosquito vector species and the impact of antiviral effects in both naturally and artificially Wolbachia-infected mosquitoes. PMID:26556361

  4. Update on Human Immunodeficiency Virus (HIV)-2 Infection

    PubMed Central

    Campbell-Yesufu, Omobolaji T.

    2011-01-01

    Infection with human immunodeficiency virus type 2 (HIV-2) occurs mainly in West Africa, but an increasing number of cases have been recognized in Europe, India, and the United States. In this era of global integration, clinicians must be aware of when to consider the diagnosis of HIV-2 infection and how to test for this virus. Although there is debate regarding when therapy should be initiated and which regimen should be chosen, recent trials have provided important information on treatment options for HIV-2 infection. In this review, we present information on recent clinical advances in our understanding of HIV-2 infection and highlight remaining diagnostic and therapeutic challenges. PMID:21367732

  5. Ultrastructural studies on dengue virus infection of human lymphoblasts.

    PubMed Central

    Sriurairatna, S; Bhamarapravati, N; Diwan, A R; Halstead, S B

    1978-01-01

    Ultrastructural studies of dengue-2 virus-infected lymphoblastoid Raji cells showed that the virus induced an increase in the size of the rough endoplasmic reticula (RER) and that the replication of the virus was confined to the cisternae of these RER. The proliferating RER formed cytoplasmic inclusions that could be seen by light microscopy. This observation could be used as evidence of a cytopathogenic effect of dengue virus on infected Rajii cells in routine cultures. Accumulation of virions in the infected cells was minimal in comparison with other cell systems, however. Sporadic clusters of mature virions were often seen on the plasma membrane. These extracellular virions were distributed adjacent to the virus-bearing RER and were presumably released virions. Vertical transmission of the virus was evident in mitotic lymphoblasts. The replication pattern of dengue virus in lymphoblastoid cells suggests that efforts should be made to determine whether blast-transformed lymphocytes, numerous in secondary dengue infections, support dengue virus replication in vivo. Images PMID:669791

  6. The naming of Potato virus Y strains infecting potato

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Potato virus Y (PVY) strain groups are based on host-response and resistance-gene interactions. The strain groups PVYO, PVYC and PVYN are well-established for the isolates infecting potato in the field. A switch in the emphasis from host response to nucleotide sequence differences in the virus genom...

  7. EFFECT OF CHLORINE TREATMENT ON INFECTIVITY OF HEPATITIS A VIRUS

    EPA Science Inventory

    This study examined the effect of chlorine treatment on the infectivity of hepatitis A virus (HAV). Prodromal chimpanzee feces, shown to induce hepatitis in marmosets (Saguinus sp.), was clarified, and the virus was precipitated with 7% polyethylene glycol 6000, harvested and res...

  8. Swine as a model for influenza A virus infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Influenza A viruses (IAV) infect a variety of hosts, including humans, swine, and various avian species. The annual influenza disease burden in the human population remains significant even with current vaccine usage and much about the pathogenesis and transmission of influenza viruses in human rema...

  9. Zucchini tigre mosaic virus infection of cucurbits in Florida

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Zucchini tigre mosaic virus (ZTMV) was identified infecting cucurbits in Florida in 2002 and again in 2015. This is the first report of ZTMV in the U.S. This report provides an overview of this emerging virus for growers, extension workers, crop consultants, and research and regulatory scientists....

  10. Whitefly Transmission of a New Virus Infecting Cucurbits in Florida

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A virus isolated from squash collected in Hillsborough County, FL in 2003, which was subsequently determined to be an ipomovirus, was transmitted by the silverleaf whitefly, Bemisia tabaci B strain in laboratory experiments. The virus was acquired by whiteflies after a 3-h access period on infected ...

  11. The Human Immunodeficiency Virus: Infectivity and Mechanisms of Pathogenesis.

    ERIC Educational Resources Information Center

    Fauci, Anthony S.

    1988-01-01

    Discusses how the infection of the human immunodeficiency virus (HIV) results in a profound immunosuppression due predominantly to a selective depletion of helper/inducer T lymphocytes that express the receptor for the virus, as well as neuropsychiatric abnormalities in the brain. (TW)

  12. Ocular syphilis in patients with Human Immunodeficiency Virus infection.

    PubMed

    Mitchell, John P; Huang, Lynn L; Rosberger, Daniel F

    2015-06-01

    As Acquired Immunodeficiency Disease (AIDS) turns thirty-years old, much progress has been made. 56,000 new cases of the Human Immunodeficiency Virus (HIV) infection are expected in Americans this year. At least half or more will be in African Americans. Reports of the association between syphilis and HIV infection are well documented. We present a case of bilateral optic neuritis and panuveitis as the initial presentation in a previously undiagnosed patient with human immunodeficiency virus (HIV) and syphilis. PMID:27269502

  13. A recombinant rabies virus expressing vesicular stomatitis virus glycoprotein fails to protect against rabies virus infection

    PubMed Central

    Foley, Heather D.; McGettigan, James P.; Siler, Catherine A.; Dietzschold, Bernhard; Schnell, Matthias J.

    2000-01-01

    To investigate the importance of the rabies virus (RV) glycoprotein (G) in protection against rabies, we constructed a recombinant RV (rRV) in which the RV G ecto- and transmembrane domains were replaced with the corresponding regions of vesicular stomatitis virus (VSV) glycoprotein (rRV-VSV-G). We were able to recover rRV-VSV-G and found that particle production was equal to rRV. However, the budding of the chimeric virus was delayed and infectious titers were reduced 10-fold compared with the parental rRV strain containing RV G. Biochemical analysis showed equal replication rates of both viruses, and similar amounts of wild-type and chimeric G were present in the respective viral particles. Additional studies were performed to determine whether the immune response against rRV-VSV-G was sufficient to protect against rabies. Mice were primed with rRV or rRV-VSV-G and challenged with a pathogenic strain of RV 12 days later. Similar immune responses against the internal viral proteins of both viruses indicated successful infection. All mice receiving the rRV vaccine survived the challenge, whereas immunization with rRV-VSV-G did not induce protection. The results confirm the crucial role of RV G in an RV vaccine. PMID:11114165

  14. Epidemiology of prolonged testicular infections with bovine viral diarrhea virus.

    PubMed

    Givens, M Daniel; Riddell, Kay P; Edmondson, Misty A; Walz, Paul H; Gard, Julie A; Zhang, Yijing; Galik, Patricia K; Brodersen, Bruce W; Carson, Robert L; Stringfellow, David A

    2009-10-20

    Previously, bovine viral diarrhea virus (BVDV) had been found in prolonged testicular infections following acute infection of immunocompetent bulls. The primary purpose of this research was to evaluate the production and maintenance of prolonged testicular infections after exposure to BVDV of seronegative bulls in varying circumstances. The secondary objective was to initiate assessment of the potential for transmission of BVDV via semen of bulls exhibiting a prolonged testicular infection. In total, 10 research trials were conducted. The first trial examined the duration of detectable virus in semen after intranasal inoculation of peri-pubertal bulls. The second to fifth trials examined the potential for prolonged testicular infections resulting from natural exposure of seronegative bulls to persistently infected heifers. In the last five trials, the potential for viral transmission from bulls exhibiting prolonged testicular infections to a small number of exposed animals (n=28) was evaluated. Results of this research demonstrated that prolonged testicular infections could result in detection of viral RNA in semen for 2.75 years with infectious virus grown from testicular tissue 12.5 months after viral exposure. A type 1b strain of BVDV caused prolonged testicular infection after natural exposure of seronegative bulls to a persistently infected heifer. However, transmission of BVDV to susceptible animals was not detected in the final five trials of this research. In conclusion, BVDV can persist in testicular tissue after acute infection for several years, but the potential for viral transmission from these prolonged testicular infections appears to be low. PMID:19473788

  15. Analysis of resistance and tolerance to virus infection in Drosophila.

    PubMed

    Merkling, Sarah H; van Rij, Ronald P

    2015-07-01

    Host defense to virus infection involves both resistance mechanisms that reduce viral burden and tolerance mechanisms that limit detrimental effects of infection. The fruit fly, Drosophila melanogaster, has emerged as a model for identifying and characterizing the genetic basis of resistance and tolerance. This protocol describes how to analyze host responses to virus infection in Drosophila, and it covers the preparation of virus stocks, experimental inoculation of flies and assessment of host survival and virus production, which are indicative of resistance or tolerance. It also provides guidance on how to account for recently identified confounding factors, including natural genetic variation in the pastrel locus and contamination of fly stocks with persistent viruses and the symbiotic bacterium Wolbachia. Our protocol aims to be accessible to newcomers to the field and, although optimized for virus research using Drosophila, some of the techniques could be adapted to other host organisms and/or other microbial pathogens. Preparation of fly stocks requires ∼1 month, virus stock preparation requires 17-20 d, virus injection and survival assays require 10-15 d and virus titration requires 14 d. PMID:26110714

  16. Correlation between Virus Replication and Antibody Responses in Macaques following Infection with Pandemic Influenza A Virus

    PubMed Central

    Koopman, Gerrit; Dekking, Liesbeth; Mortier, Daniëlla; Nieuwenhuis, Ivonne G.; van Heteren, Melanie; Kuipers, Harmjan; Remarque, Edmond J.; Radošević, Katarina; Bogers, Willy M. J. M.

    2015-01-01

    ABSTRACT Influenza virus infection of nonhuman primates is a well-established animal model for studying pathogenesis and for evaluating prophylactic and therapeutic intervention strategies. However, usually a standard dose is used for the infection, and there is no information on the relation between challenge dose and virus replication or the induction of immune responses. Such information is also very scarce for humans and largely confined to evaluation of attenuated virus strains. Here, we have compared the effect of a commonly used dose (4 × 106 50% tissue culture infective doses) versus a 100-fold-higher dose, administered by intrabronchial installation, to two groups of 6 cynomolgus macaques. Animals infected with the high virus dose showed more fever and had higher peak levels of gamma interferon in the blood. However, virus replication in the trachea was not significantly different between the groups, although in 2 out of 6 animals from the high-dose group it was present at higher levels and for a longer duration. The virus-specific antibody response was not significantly different between the groups. However, antibody enzyme-linked immunosorbent assay, virus neutralization, and hemagglutination inhibition antibody titers correlated with cumulative virus production in the trachea. In conclusion, using influenza virus infection in cynomolgus macaques as a model, we demonstrated a relationship between the level of virus production upon infection and induction of functional antibody responses against the virus. IMPORTANCE There is only very limited information on the effect of virus inoculation dose on the level of virus production and the induction of adaptive immune responses in humans or nonhuman primates. We found only a marginal and variable effect of virus dose on virus production in the trachea but a significant effect on body temperature. The induction of functional antibody responses, including virus neutralization titer, hemagglutination inhibition

  17. Cognitive dysfunction and hepatitis C virus infection

    PubMed Central

    Solinas, Antonio; Piras, Maria Rita; Deplano, Angelo

    2015-01-01

    Cognitive dysfunction in patients with chronic hepatitis C virus (HCV) infection is a distinct form of minimal hepatic encephalopathy (MHE). In fact, the majority of HCV-positive patients, irrespective of the grading of liver fibrosis, display alterations of verbal learning, attention, executive function, and memory when they are evaluated by suitable neuropsychological tests. Similarities between the cognitive dysfunction of HCV patients and MHE of patients with different etiologies are unclear. It is also unknown how the metabolic alterations of advanced liver diseases interact with the HCV-induced cognitive dysfunction, and whether these alterations are reversed by antiviral therapies. HCV replication in the brain may play a role in the pathogenesis of neuroinflammation. HCV-related brain dysfunction may be associated with white matter neuronal loss, alterations of association tracts and perfusion. It is unclear to what extent, in patients with cirrhosis, HCV triggers an irreversible neurodegenerative brain damage. New insights on this issue will be provided by longitudinal studies using the protocols established by the diagnostic and statistical manual of mental disorders fifth edition for cognitive disorders. The domains to be evaluated are complex attention; executive functions; learning and memory; perceptual motor functions; social cognition. These evaluations should be associated with fluorodeoxyglucose positron emission tomography and magnetic resonance imaging (MRI) protocols for major cognitive disorders including magnetic resonance spectroscopy, diffusion tensor imaging, magnetic resonance perfusion, and functional MRI. Also, the characteristics of portal hypertension, including the extent of liver blood flow and the type of portal shunts, should be evaluated. PMID:25954475

  18. Monoclonal antibody therapy for Junin virus infection.

    PubMed

    Zeitlin, Larry; Geisbert, Joan B; Deer, Daniel J; Fenton, Karla A; Bohorov, Ognian; Bohorova, Natasha; Goodman, Charles; Kim, Do; Hiatt, Andrew; Pauly, Michael H; Velasco, Jesus; Whaley, Kevin J; Altmann, Friedrich; Gruber, Clemens; Steinkellner, Herta; Honko, Anna N; Kuehne, Ana I; Aman, M Javad; Sahandi, Sara; Enterlein, Sven; Zhan, Xiaoguo; Enria, Delia; Geisbert, Thomas W

    2016-04-19

    Countermeasures against potential biothreat agents remain important to US Homeland Security, and many of these pharmaceuticals could have dual use in the improvement of global public health. Junin virus, the causative agent of Argentine hemorrhagic fever (AHF), is an arenavirus identified as a category A high-priority agent. There are no Food and Drug Administration (FDA) approved drugs available for preventing or treating AHF, and the current treatment option is limited to administration of immune plasma. Whereas immune plasma demonstrates the feasibility of passive immunotherapy, it is limited in quantity, variable in quality, and poses safety risks such as transmission of transfusion-borne diseases. In an effort to develop a monoclonal antibody (mAb)-based alternative to plasma, three previously described neutralizing murine mAbs were expressed as mouse-human chimeric antibodies and evaluated in the guinea pig model of AHF. These mAbs provided 100% protection against lethal challenge when administered 2 d after infection (dpi), and one of them (J199) was capable of providing 100% protection when treatment was initiated 6 dpi and 92% protection when initiated 7 dpi. The efficacy of J199 is superior to that previously described for all other evaluated drugs, and its high potency suggests that mAbs like J199 offer an economical alternative to immune plasma and an effective dual use (bioterrorism/public health) therapeutic. PMID:27044104

  19. Monoclonal antibody therapy for Junin virus infection

    PubMed Central

    Zeitlin, Larry; Geisbert, Joan B.; Deer, Daniel J.; Fenton, Karla A.; Bohorov, Ognian; Bohorova, Natasha; Goodman, Charles; Kim, Do; Hiatt, Andrew; Pauly, Michael H.; Velasco, Jesus; Whaley, Kevin J.; Altmann, Friedrich; Gruber, Clemens; Steinkellner, Herta; Honko, Anna N.; Kuehne, Ana I.; Aman, M. Javad; Sahandi, Sara; Enterlein, Sven; Zhan, Xiaoguo; Enria, Delia; Geisbert, Thomas W.

    2016-01-01

    Countermeasures against potential biothreat agents remain important to US Homeland Security, and many of these pharmaceuticals could have dual use in the improvement of global public health. Junin virus, the causative agent of Argentine hemorrhagic fever (AHF), is an arenavirus identified as a category A high-priority agent. There are no Food and Drug Administration (FDA) approved drugs available for preventing or treating AHF, and the current treatment option is limited to administration of immune plasma. Whereas immune plasma demonstrates the feasibility of passive immunotherapy, it is limited in quantity, variable in quality, and poses safety risks such as transmission of transfusion-borne diseases. In an effort to develop a monoclonal antibody (mAb)-based alternative to plasma, three previously described neutralizing murine mAbs were expressed as mouse-human chimeric antibodies and evaluated in the guinea pig model of AHF. These mAbs provided 100% protection against lethal challenge when administered 2 d after infection (dpi), and one of them (J199) was capable of providing 100% protection when treatment was initiated 6 dpi and 92% protection when initiated 7 dpi. The efficacy of J199 is superior to that previously described for all other evaluated drugs, and its high potency suggests that mAbs like J199 offer an economical alternative to immune plasma and an effective dual use (bioterrorism/public health) therapeutic. PMID:27044104

  20. Infectious salmon anaemia virus (ISAV) mucosal infection in Atlantic salmon.

    PubMed

    Aamelfot, Maria; McBeath, Alastair; Christiansen, Debes H; Matejusova, Iveta; Falk, Knut

    2015-01-01

    All viruses infecting fish must cross the surface mucosal barrier to successfully enter a host. Infectious salmon anaemia virus (ISAV), the causative agent of the economically important infectious salmon anaemia (ISA) in Atlantic salmon, Salmo salar L., has been shown to use the gills as its entry point. However, other entry ports have not been investigated despite the expression of virus receptors on the surface of epithelial cells in the skin, the gastrointestinal (GI) tract and the conjunctiva. Here we investigate the ISAV mucosal infection in Atlantic salmon after experimental immersion (bath) challenge and in farmed fish collected from a confirmed outbreak of ISA in Norway. We show for the first time evidence of early replication in several mucosal surfaces in addition to the gills, including the pectoral fin, skin and GI tract suggesting several potential entry points for the virus. Initially, the infection is localized and primarily infecting epithelial cells, however at later stages it becomes systemic, infecting the endothelial cells lining the circulatory system. Viruses of low and high virulence used in the challenge revealed possible variation in virus progression during infection at the mucosal surfaces. PMID:26490835

  1. Concordance of interim and final estimates of influenza vaccine effectiveness: a systematic review.

    PubMed

    Leung, Vivian K; Cowling, Benjamin J; Feng, Shuo; Sullivan, Sheena G

    2016-04-21

    The World Health Organization's Global Influenza Surveillance and Response System meets twice a year to generate a recommendation for the composition of the seasonal influenza vaccine. Interim vaccine effectiveness (VE) estimates provide a preliminary indication of influenza vaccine performance during the season and may be useful for decision making. We reviewed 17 pairs of studies reporting 33 pairs of interim and final estimates using the test-negative design to evaluate whether interim estimates can reliably predict final estimates. We examined features of the study design that may be correlated with interim estimates being substantially different from their final estimates and identified differences related to change in study period and concomitant changes in sample size, proportion vaccinated and proportion of cases. An absolute difference of no more than 10% between interim and final estimates was found for 18 of 33 reported pairs of estimates, including six of 12 pairs reporting VE against any influenza, six of 10 for influenza A(H1N1)pdm09, four of seven for influenza A(H3N2) and two of four for influenza B. While we identified inconsistencies in the methods, the similarities between interim and final estimates support the utility of generating and disseminating preliminary estimates of VE while virus circulation is ongoing. PMID:27124573

  2. Zika virus infections imported from Brazil to Portugal, 2015.

    PubMed

    Zé-Zé, L; Prata, M B; Teixeira, T; Marques, N; Mondragão, A; Fernandes, R; Saraiva da Cunha, J; Alves, M J

    2016-01-01

    Zika virus is an emerging arbovirus transmitted by Aedes sp. mosquitoes like the Dengue and Chikungunya viruses. Zika virus was until recently considered a mild pathogenic mosquito-borne flavivirus with very few reported benign human infections. In 2007, an epidemic in Micronesia initiated the turnover in the epidemiological history of Zika virus and more recently, the potential association with congenital microcephaly cases in Brazil 2015, still under investigation, led the World Health Organization (WHO) to declare a Public Health Emergency of International Concern on February 1, 2016. Here, we present the clinical and laboratory aspects related to the first four imported human cases of Zika virus in Portugal from Brazil, and alert, regarding the high level of traveling between Portugal and Brazil, and the ongoing expansion of this virus in the Americas, for the threat for Zika virus introduction in Europe and the possible introduction to Madeira Island where Aedes aegypti is present. PMID:27134823

  3. Zika virus infections imported from Brazil to Portugal, 2015

    PubMed Central

    Zé-Zé, L.; Prata, M.B.; Teixeira, T.; Marques, N.; Mondragão, A.; Fernandes, R.; Saraiva da Cunha, J.; Alves, M.J.

    2016-01-01

    Zika virus is an emerging arbovirus transmitted by Aedes sp. mosquitoes like the Dengue and Chikungunya viruses. Zika virus was until recently considered a mild pathogenic mosquito-borne flavivirus with very few reported benign human infections. In 2007, an epidemic in Micronesia initiated the turnover in the epidemiological history of Zika virus and more recently, the potential association with congenital microcephaly cases in Brazil 2015, still under investigation, led the World Health Organization (WHO) to declare a Public Health Emergency of International Concern on February 1, 2016. Here, we present the clinical and laboratory aspects related to the first four imported human cases of Zika virus in Portugal from Brazil, and alert, regarding the high level of traveling between Portugal and Brazil, and the ongoing expansion of this virus in the Americas, for the threat for Zika virus introduction in Europe and the possible introduction to Madeira Island where Aedes aegypti is present. PMID:27134823

  4. First case of imported Zika virus infection in Spain.

    PubMed

    Bachiller-Luque, Pablo; Domínguez-Gil González, Marta; Álvarez-Manzanares, Jesús; Vázquez, Ana; De Ory, Fernando; Sánchez-Seco Fariñas, M Paz

    2016-04-01

    We report a case of Zika virus (ZIKV) infection in a patient with diarrhea, fever, synovitis, non-purulent conjunctivitis, and with discreet retro-orbital pain, after returning from Colombia in January 2016. The patient referred several mosquito bites. Presence of ZIKV was detected by PCR (polymerase chain reaction) in plasma. Rapid microbiological diagnosis of ZIKV infection is needed in European countries with circulation of its vector, in order to avoid autochthonous circulation. The recent association of ZIKV infection with abortion and microcephaly, and a Guillain-Barré syndrome highlights the need for laboratory differentiation of ZIKV from other virus infection. Women with potential risk for Zika virus infection who are pregnant or planning to become pregnant must mention that fact during prenatal visits in order to be evaluated and properly monitored. PMID:26994814

  5. Infection of Mosquito Cells (C6/36) by Dengue-2 Virus Interferes with Subsequent Infection by Yellow Fever Virus.

    PubMed

    Abrao, Emiliana Pereira; da Fonseca, Benedito Antônio Lopes

    2016-02-01

    Dengue is one of the most important diseases caused by arboviruses in the world. Yellow fever is another arthropod-borne disease of great importance to public health that is endemic to tropical regions of Africa and the Americas. Both yellow fever and dengue viruses are flaviviruses transmitted by Aedes aegypti mosquitoes, and then, it is reasonable to consider that in a given moment, mosquito cells could be coinfected by both viruses. Therefore, we decided to evaluate if sequential infections of dengue and yellow fever viruses (and vice-versa) in mosquito cells could affect the virus replication patterns. Using immunofluorescence and real-time PCR-based replication assays in Aedes albopictus C6/36 cells with single or sequential infections with both viruses, we demonstrated the occurrence of viral interference, also called superinfection exclusion, between these two viruses. Our results show that this interference pattern is particularly evident when cells were first infected with dengue virus and subsequently with yellow fever virus (YFV). Reduction in dengue virus replication, although to a lower extent, was also observed when C6/36 cells were initially infected with YFV followed by dengue virus infection. Although the importance that these findings have on nature is unknown, this study provides evidence, at the cellular level, of the occurrence of replication interference between dengue and yellow fever viruses and raises the question if superinfection exclusion could be a possible explanation, at least partially, for the reported lack of urban yellow fever occurrence in regions where a high level of dengue transmission occurs. PMID:26808727

  6. Effect of Cell Physiological State on Infection by Rat Virus

    PubMed Central

    Tennant, Raymond W.; Layman, Kenneth R.; Hand, Russell E.

    1969-01-01

    Infection by rat virus has been studied in cultures of rat embryo cells to evaluate the Margolis-Kilham hypothesis that the virus preferentially infects tissues with actively dividing cells. An enhancement of infection was seen in cultures infected 10 hr after fresh medium was added as compared to infection of stationary cultures (infected before addition of fresh medium). Since addition of fresh medium stimulates deoxyribonucleic acid (DNA) synthesis, the number of cells per culture synthesizing DNA at the time of infection was compared with the proportion of cells which synthesized viral protein. Cells were infected before the medium change and 10 or 24 hr after the medium change and were pulse-labeled with 3H-thymidine at the time virus was added. The cells were allowed to initiate viral protein synthesis before they were fixed and stained with fluorescein-conjugated anti-rat virus serum. Fluorescence microscopy permitted both labels to be counted simultaneouly and showed that the greatest proportion of cells synthesizing viral protein were those which had incorporated 3H-thymidine at the time of infection. Images PMID:16789120

  7. Experimental co-infection studies with avian influenza viruses and Newcastle Disease viruses in chickens, turkeys and domestic ducks

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Co-infections of poultry with Newcastle Disease viruses (NDVs) and Avian Influenza viruses (AIVs) present a problem both from the clinical point of view and the diagnosis of these viruses. Little has been done to understand the interactions between these two viruses when infecting poultry. Exposur...

  8. Co-infection and disease severity of Ohio Maize dwarf mosaic virus and Maize chlorotic dwarf virus strains

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Two major maize viruses have been reported in the United States: Maize dwarf mosaic virus (MDMV) and Maize chlorotic dwarf virus (MCDV). These viruses co-occur in regions where maize is grown such that co-infections are likely. Co-infection of different strains of MCDV is also observed frequently...

  9. Senescence affects endothelial cells susceptibility to dengue virus infection.

    PubMed

    AbuBakar, Sazaly; Shu, Meng-Hooi; Johari, Jefree; Wong, Pooi-Fong

    2014-01-01

    Alteration in the endothelium leading to increased vascular permeability contributes to plasma leakage seen in dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). An earlier study showed that senescent endothelial cells (ECs) altered the ECs permeability. Here we investigated the susceptibility of senescing human umbilical vein endothelial cells (HUVECs) to dengue virus infection and determined if dengue virus infection induces HUVECs senescence. Our results suggest that DENV type-2 (DENV-2) foci forming unit (FFU) and extracellular virus RNA copy number were reduced by at least 35% and 85% in infection of the intermediate young and early senescent HUVECs, respectively, in comparison to infection of young HUVECs. No to low infectivity was recovered from infection of late senescent HUVECs. DENV infection also increases the percentage of HUVECs expressing senescence-associated (SA)-β-gal, cells arrested at the G2/M phase or 4N DNA content stage and cells with enlarged morphology, indicative of senescing cells. Alteration of HUVECs morphology was recorded using impedance-based real-time cell analysis system following DENV-2 infection. These results suggest that senescing HUVECs do not support DENV infection and DENV infection induces HUVECs senescence. The finding highlights the possible role of induction of senescence in DENV infection of the endothelial cells. PMID:24782642

  10. Reduced Risk of Disease During Postsecondary Dengue Virus Infections

    PubMed Central

    Olkowski, Sandra; Forshey, Brett M.; Morrison, Amy C.; Rocha, Claudio; Vilcarromero, Stalin; Halsey, Eric S.; Kochel, Tadeusz J.; Scott, Thomas W.; Stoddard, Steven T.

    2013-01-01

    Background. Antibodies induced by infection with any 1 of 4 dengue virus (DENV) serotypes (DENV-1–4) may influence the clinical outcome of subsequent heterologous infections. To quantify potential cross-protective effects, we estimated disease risk as a function of DENV infection, using data from longitudinal studies performed from September 2006 through February 2011 in Iquitos, Peru, during periods of DENV-3 and DENV-4 transmission. Methods. DENV infections before and during the study period were determined by analysis of serial serum samples with virus neutralization tests. Third and fourth infections were classified as postsecondary infections. Dengue fever cases were detected by door-to-door surveillance for acute febrile illness. Results. Among susceptible participants, 39% (420/1077) and 53% (1595/2997) seroconverted to DENV-3 and DENV-4, respectively. Disease was detected in 7% of DENV-3 infections and 10% of DENV-4 infections. Disease during postsecondary infections was reduced by 93% for DENV-3 and 64% for DENV-4, compared with primary and secondary infections. Despite lower disease rates, postsecondary infections constituted a significant proportion of apparent infections (14% [for DENV-3 infections], 45% [for DENV-4 infections]). Conclusions. Preexisting heterotypic antibodies markedly reduced but did not eliminate the risk of disease in this study population. These results improve understanding of how preinfection history can be associated with dengue outcomes and DENV transmission dynamics. PMID:23776195

  11. Drosophila C Virus Systemic Infection Leads to Intestinal Obstruction

    PubMed Central

    Chtarbanova, Stanislava; Lamiable, Olivier; Lee, Kwang-Zin; Galiana, Delphine; Troxler, Laurent; Meignin, Carine; Hetru, Charles; Hoffmann, Jules A.; Daeffler, Laurent

    2014-01-01

    ABSTRACT Drosophila C virus (DCV) is a positive-sense RNA virus belonging to the Dicistroviridae family. This natural pathogen of the model organism Drosophila melanogaster is commonly used to investigate antiviral host defense in flies, which involves both RNA interference and inducible responses. Although lethality is used routinely as a readout for the efficiency of the antiviral immune response in these studies, virus-induced pathologies in flies still are poorly understood. Here, we characterize the pathogenesis associated with systemic DCV infection. Comparison of the transcriptome of flies infected with DCV or two other positive-sense RNA viruses, Flock House virus and Sindbis virus, reveals that DCV infection, unlike those of the other two viruses, represses the expression of a large number of genes. Several of these genes are expressed specifically in the midgut and also are repressed by starvation. We show that systemic DCV infection triggers a nutritional stress in Drosophila which results from intestinal obstruction with the accumulation of peritrophic matrix at the entry of the midgut and the accumulation of the food ingested in the crop, a blind muscular food storage organ. The related virus cricket paralysis virus (CrPV), which efficiently grows in Drosophila, does not trigger this pathology. We show that DCV, but not CrPV, infects the smooth muscles surrounding the crop, causing extensive cytopathology and strongly reducing the rate of contractions. We conclude that the pathogenesis associated with systemic DCV infection results from the tropism of the virus for an important organ within the foregut of dipteran insects, the crop. IMPORTANCE DCV is one of the few identified natural viral pathogens affecting the model organism Drosophila melanogaster. As such, it is an important virus for the deciphering of host-virus interactions in insects. We characterize here the pathogenesis associated with DCV infection in flies and show that it results from the

  12. Chronic West Nile virus infection in kea (Nestor notabilis).

    PubMed

    Bakonyi, Tamás; Gajdon, Gyula K; Schwing, Raoul; Vogl, Wolfgang; Häbich, Annett-Carolin; Thaller, Denise; Weissenböck, Herbert; Rudolf, Ivo; Hubálek, Zdenek; Nowotny, Norbert

    2016-02-01

    Six kea (Nestor notabilis) in human care, naturally infected with West Nile virus (WNV) lineage 2 in Vienna, Austria, in 2008, developed mild to fatal neurological signs. WNV RNA persisted and the virus evolved in the birds' brains, as demonstrated by (phylo)genetic analyses of the complete viral genomes detected in kea euthanized between 2009 and 2014. WNV antibodies persisted in the birds, too. Chronic WNV infection in the brain might contribute to the circulation of the virus through oral transmission to predatory birds. PMID:26790946

  13. Natural infection of turkeys by infectious laryngotracheitis virus.

    PubMed

    Portz, Cristiana; Beltrão, Nilzane; Furian, Thales Quedi; Júnior, Alfredo Bianco; Macagnan, Marisa; Griebeler, Josiane; Lima Rosa, Carlos André Veiga; Colodel, Edson Moleta; Driemeier, David; Back, Alberto; Barth Schatzmayr, Ortrud Monika; Canal, Cláudio Wageck

    2008-09-18

    The infectious laryngotracheitis virus (ILTV) is an important respiratory pathogen of chickens that also infects pheasants and peafowl. Epidemiologically non-related commercial turkey flocks with clinical signs such as tracheitis, swollen sinuses, conjunctivitis and expectoration of bloody mucus were examined for the presence of the virus. Laboratory ILTV detection was performed by virus isolation in embryonated eggs and cell cultures, PCR and sequencing of amplification products, histopathology, indirect immunofluorescence and electron microscopy. One ILTV turkey isolate was also experimentally inoculated into susceptible chickens and turkeys, reproducing a mild respiratory disease. This is the first description of natural infections with ILTV in turkeys. PMID:18436397

  14. Characteristics of mild dengue virus infection in Thai children.

    PubMed

    Yoon, In-Kyu; Srikiatkhachorn, Anon; Hermann, Laura; Buddhari, Darunee; Scott, Thomas W; Jarman, Richard G; Aldstadt, Jared; Nisalak, Ananda; Thammapalo, Suwich; Bhoomiboonchoo, Piraya; Mammen, Mammen P; Green, Sharone; Gibbons, Robert V; Endy, Timothy P; Rothman, Alan L

    2013-12-01

    A four-year longitudinal cohort and geographic cluster study in rural Thailand was conducted to characterize the clinical spectrum of dengue virus (DENV) infection. Symptomatic DENV infections in the cohort were detected by active school absence-based surveillance that triggered cluster investigations around ill cohort children. Data from 189 cohort children with symptomatic DENV infection and 126 contact children in the clusters with DENV infection were analyzed. Of infected contacts, only 19% were asymptomatic; 81% were symptomatic, but only 65.9% reported fever. Symptom-based case definitions were unreliable for diagnosis. Symptomatic infections in contacts were milder with lower DENV RNA levels than the cohort. Infections in contacts with fever history were more likely to have detectable DENV RNA than infections without fever history. Mild infections identified by cluster investigations account for a major proportion of all DENV infections. These findings are relevant for disease burden assessments, transmission modeling, and determination of vaccine impact. PMID:24127167

  15. The Aedes aegypti Toll Pathway Controls Dengue Virus Infection

    PubMed Central

    Xi, Zhiyong; Ramirez, Jose L.; Dimopoulos, George

    2008-01-01

    Aedes aegypti, the mosquito vector of dengue viruses, utilizes its innate immune system to ward off a variety of pathogens, some of which can cause disease in humans. To date, the features of insects' innate immune defenses against viruses have mainly been studied in the fruit fly Drosophila melanogaster, which appears to utilize different immune pathways against different types of viruses, in addition to an RNA interference–based defense system. We have used the recently released whole-genome sequence of the Ae. aegypti mosquito, in combination with high-throughput gene expression and RNA interference (RNAi)-based reverse genetic analyses, to characterize its response to dengue virus infection in different body compartments. We have further addressed the impact of the mosquito's endogenous microbial flora on virus infection. Our findings indicate a significant role for the Toll pathway in regulating resistance to dengue virus, as indicated by an infection-responsive regulation and functional assessment of several Toll pathway–associated genes. We have also shown that the mosquito's natural microbiota play a role in modulating the dengue virus infection, possibly through basal-level stimulation of the Toll immune pathway. PMID:18604274

  16. Ethnicity, deprivation and mortality due to 2009 pandemic influenza A(H1N1) in England during the 2009/2010 pandemic and the first post-pandemic season.

    PubMed

    Zhao, H; Harris, R J; Ellis, J; Pebody, R G

    2015-12-01

    The relationship between risk of death following influenza A(H1N1)pdm09 infection and ethnicity and deprivation during the 2009/2010 pandemic period and the first post-pandemic season of 2010/2011 in England was examined. Poisson regression models were used to estimate the mortality risk, adjusted for age, gender, and place of residence. Those of non-White ethnicity experienced an increased mortality risk compared to White populations during the 2009/2010 pandemic [10·5/1000 vs. 6·0/1000 general population; adjusted risk ratio (RR) 1·84, 95% confidence interval (CI) 1·39-2·54] with the highest risk in those of Pakistani ethnicity. However, no significant difference between ethnicities was observed during the following 2010/2011 season. Persons living in areas with the highest level of deprivation had a significantly higher risk of death (RR 2·08, 95% CI 1·49-2·91) compared to the lowest level for both periods. These results highlight the importance of rapid identification of groups at higher risk of severe disease in the early stages of future pandemics to enable the implementation of optimal prevention and control measures for vulnerable populations. PMID:25850904

  17. [Border disease: a persistent virus infection in sheep (author's transl)].

    PubMed

    Terpstra, C

    1980-08-15

    Border disease (BD) is a congenital infection of sheep characterised by still-birth, abortion and the birth of weak lambs with nervous symptoms and sometimes an abnormally hairy birthcoat. The lambs are almost constantly trembling or shaking, they often have an erratic gait and in severe cases are unable to rise. The nervous signs are due to a defective myelinogensis of the central nervous system and tend to disappear at a later age. Many affected lambs die shortly after birth and those which survive usually show retarded growth. The disease is caused by a virus which is closely related to the virus of bovine virus diarrhoea (BVD). The virus may be isolated from every organ and is excreted with saliva, nasal discharge, urine and faeces. Clinically the diagnosis can be made with high probability when nervous signs and hairy birthcoat are both present. Laboratory diagnosis is based on the detection of antigen by immunofluorescence or virus isolation. In addition ewes of BD-affected lambs usually possess antibodies against BVD-virus. In some lambs, an immune response starts during prenatal life, others show a transient or lasting low level response at a later age, whereas still others remained serologically negative for at least 2 1/2 years. Asymptomatic virus carriers occur among lambs as well as among adult sheep. The persistently infected animals are continously shedding virus and thus maintain the infection in the flock. PMID:6252652

  18. Respiratory Syncytial Virus Infection (RSV): Infection and Incidence

    MedlinePlus

    ... Links Unexplained Respiratory Disease Outbreaks Red Book® Online Infection and Incidence Recommend on Facebook Tweet Share Compartir RSV can cause upper respiratory infections (such as colds) and lower respiratory tract infections ( ...

  19. Occurrence of viruses infecting pea in Iran.

    PubMed

    Esfandiari, N; Kohi-Habibi, M; Mosahebi, Gh

    2006-01-01

    A survey was conducted to determine the incidence of Alfalfa mosaic virus (AMV), Bean yellow mosaic virus (BYMV), Broad bean wilt virus-1 (BBWV), Pea leafroll virus (PLRV), Pea enation mosaic virus (PEMV), Pea seed borne mosaic virus (PSbMV), Potato virus x(PVX), Tomato mosaic virus (ToMV), Tomato spotted wilt virus (TSWV) on pea (Pisum sativum) in Iran. A Total of 1276 random and 684 symptomatic pea samples were collected during the spring and summer of 2002-2004 in Tehran province of Iran, where pea is grown, and tested by enzyme-linked immunosorbent assay (ELISA) using specific polyclonal antibodies. Serological diagnoses were confirmed by electron microscopy and host range studies. Incidence of viruses in decreasing order was PVX (69%), ToMV (59%), PSbMV (36.6%), BBWV-1 (26.1%), BYMV (20.3%), AMV (17.77%), TSWV (12.6%), PEMV (10.9%), PLRV (6.78%). In this survey, natural occurrence of AMV, BBWV-1, PSbMV, TSWV, PVX and ToMV was reported for the first time on the pea in Iran. PMID:17390891

  20. Immunity to Polyomavirus Infection: The Polyoma Virus-Mouse Model

    PubMed Central

    Swanson, Phillip A.; Lukacher, Aron E.; Szomolanyi-Tsuda, Eva

    2009-01-01

    A ubiquitous clinically silent murine pathogen, polyoma virus has enjoyed long-term co-evolution with the mouse, a highly tractable and genetically and immunologically informative small animal model. Thus, polyoma virus has provided a valuable experimental construct to decipher the host immune mechanisms that come into play to control systemic low-level persistent viral infections. Impaired immunosurveillance for infected cells puts the murine host at risk both to injury resulting from excessive direct virus cytolysis and development of virus-induced tumors. In this review, we present our current understanding of the multifaceted immune response invoked by the mouse to maintain détente with this potentially deleterious persistent natural pathogen, and discuss implications of these studies for therapeutic interventions for human polyomavirus infection. PMID:19505652

  1. Zika Virus Infection and Development of a Murine Model.

    PubMed

    Shah, Ankit; Kumar, Anil

    2016-08-01

    In view of the recent outbreak of Zika virus (ZIKV), there is an urgent need to investigate the pathogenesis of the symptoms associated with ZIKV infection. Since the first identification of the virus in 1947, the pathologies associated with ZIKV infection were thought to be limited with mild illness that presented fever, rashes, muscle aches, and weakness. However, ZIKV infection has been shown to cause Guillain-Barré Syndrome, and numerous cases of congenital microcephaly in children have been reported when pregnant females were exposed to the virus. The severity and the rate of spread of ZIKV in the last year has drawn alarming interest among researchers to investigate murine models to study viral pathogenesis and develop candidate vaccines. A recent study by Lazear and colleagues, in the May 2016 issue of cell host and microbe, is an effort to study the pathogenesis of contemporary and historical virus strains in various mouse models. PMID:27260223

  2. Intrauterine herpes simplex virus infection presenting with hypopigmented lesions.

    PubMed

    Low, Lynette C M; Carton, James; Walker, Marjorie; Tudor-Williams, Gareth; Hardman, Catherine

    2012-01-01

    Genital herpes simplex virus (HSV) is a sexually transmitted infection that can be transmitted from mother to child in utero, perinatally, or postnatally. Cutaneous infection with HSV commonly presents as vesicles affecting the skin, eyes, or mouth. In our case, we report a well child with cutaneous hypopigmented patches at birth that preceded typical blistering. PMID:22010816

  3. Heart and Skeletal Muscle Are Targets of Dengue Virus Infection

    PubMed Central

    Salgado, Doris Martha; Eltit, José Miguel; Mansfield, Keith; Panqueba, César; Castro, Dolly; Vega, Martha Rocio; Xhaja, Kris; Schmidt, Diane; Martin, Katherine J.; Allen, Paul D.; Rodriguez, Jairo Antonio; Dinsmore, Jonathan H.; López, José Rafael; Bosch, Irene

    2010-01-01

    Background Dengue fever is one of the most significant re-emerging tropical diseases, despite our expanding knowledge of the disease, viral tropism is still not known to target heart tissues or muscle. Methods A prospective pediatric clinical cohort of 102 dengue hemorrhagic fever patients from Colombia, South America, was followed for 1 year. Clinical diagnosis of myocarditis was routinely performed. Electrocardiograph and echocardiograph analysis were performed to confirm those cases. Immunohistochemistry for detection of dengue virus and inflammatory markers was performed on autopsied heart tissue. In vitro studies of human striated skeletal fibers (myotubes) infected with dengue virus were used as a model for myocyte infection. Measurements of intracellular Ca2+ concentration as well as immunodetection of dengue virus and inflammation markers in infected myotubes were performed. Results Eleven children with dengue hemorrhagic fever presented with symptoms of myocarditis. Widespread viral infection of the heart, myocardial endothelium, and cardiomyocytes, accompanied by inflammation was observed in 1 fatal case. Immunofluorescence confocal microscopy showed that myotubes were infected by dengue virus and had increased expression of the inflammatory genes and protein IP-10. The infected myotubes also had increases in intracellular Ca2+ concentration. Conclusions Vigorous infection of heart tissues in vivo and striated skeletal cells in vitro are demonstrated. Derangements of Ca2+ storage in the infected cells may directly contribute to the presentation of myocarditis in pediatric patients. PMID:20032806

  4. Clinical bovine viral diarrhoea virus infection in Jordan.

    PubMed

    Abutarbush, S M; Alqawasmeh, D M

    2010-12-01

    A 1-year-old Holstein Friesian heifer was presented for anorexia and acute diarrhoea. The heifer was born and raised at the farm. Bovine viral diarrhoea virus (BVDV) infection was diagnosed using clinical signs and RT-PCR. Clinical BVDV infection has never been reported in Jordan. PMID:21117287

  5. Evidence of Apis cerana sacbrood virus infection in Apis mellifera

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sacbrood virus (SBV) is one of the most serious threats to Apis cerana but is much less destructive to Apis mellifera. In previous studies, SBV isolates infecting A. cerana and A. mellifera were identified as different serotypes, suggesting a species-barrier of SBV infection. In order to clarify whe...

  6. ZIKA VIRUS INFECTION; VERTICAL TRANSMISSION AND FOETAL CONGENITAL ANOMALIES.

    PubMed

    Abbasi, Aziz-un-Nisa

    2016-01-01

    Zika virus (ZIKV) is an arbovirus belonging to flaviviridae family that includes Dengue, West Nile, and Yellow Fever among others. Zika virus was first discovered in 1947 in Zika forest of Uganda. It is a vector borne disease, which has been sporadically reported mostly from Africa, Pacific islands and Southeast Asia since its discovery. ZIKV infection presents as a mild illness with symptoms lasting for several days to a week after the bite of an infected mosquito. Majority of the patients have low grade fever, rash, headaches, joints pain, myalgia, and flu like symptoms. Pregnant women are more vulnerable to ZIKV infection and serious congenital anomalies can occur in foetus through trans-placental transmission. The gestation at which infection is acquired is important. Zika virus infection acquired in early pregnancy poses greater risk. There is no evidence so far about transmission through breast milk. Foetal microcephaly, Gillian Barre syndrome and other neurological and autoimmune syndromes have been reported in areas where Zika outbreaks have occurred. As infection is usually very mild no specific treatment is required. Pregnant women may be advised to take rest, get plenty of fluids. For fever and pain they can take antipyretics like paracetamol. So far no specific drugs or vaccines are available against Zika Virus Infection so prevention is the mainstay against this diseases. As ZIKV infection is a vector borne disease, prevention can be a multi-pronged strategy. These entail vector control interventions, personal protection, environmental sanitation and health education among others. PMID:27323550

  7. [Dementia and human inmmunodeficiency virus infection].

    PubMed

    Gray, F

    1998-01-01

    HIV-associated neurological manifestations: dementia, myelopathy, and neuropathy, have become one of the commonest causes of neurological disorders in young people. Cognitive impairment develops in about 30 p. 100 of patients with AIDS and frank dementia in 15 to 20 p. 100 with an annual incidence after AIDS of approximatively 7 p. 100. Typically, the onset of dementia is relatively abrupt over a few weeks or months. The clinical manifestations of the encephalopathy now termed "HIV-dementia", suggest predominant subcortical or frontal involvement. Typical presentation includes apathy and inertia, memory loss and cognitive slowing, minor depressive symptoms and withdrawal from usual activities. Neurological examination may show hypertonia of lower limbs, tremor, clonus, frontal release signs and hyperactive reflexes. Terminally, the patient is bedbound, incontinent, abulic or mute with decorticate posturing leading to death over 3 to 6 months. However, a stabilisation and even a regression of the cognitive disorders have been observed following antiretroviral treatment. Radiological features of HIV dementia include both central and cortical atrophy and white matter rarefaction. However they are neither invariable nor specific. Together with CSF examination, they are more important to exclude opportunistic infections. Indeed, although a completely normal CSF profile may reasonably exclude the diagnosis; at present, no single test or combination of tests can reliably diagnose HIV dementia. Although the clinical characteristics of HIV-dementia are now clearly established, its pathogenesis is unclear and its pathological counterpart remains a matter of debate. A number of "HIV-induced" lesions may be found in the brain of AIDS patients and their causative role in HIV-dementia has been considered. They include HIV encephalitis due to productive CNS infection by the virus, diffuse white matter pallor "HIV-leukoencephalopathy" reflecting an abnormality of the blood brain

  8. Chemokine antagonism in chronic hepatitis C virus infection.

    PubMed

    Charles, Edgar D; Dustin, Lynn B

    2011-01-01

    Immune responses to hepatitis C virus (HCV) fail to clear the virus in most individuals. Why patients who are less likely to clear HCV infection have high plasma levels of CXCL10 (also known as IP-10), a chemokine that directs T cells to sites of infection, has long been unclear. In this issue of the JCI, Casrouge and colleagues shed light on this paradox by showing that CXCL10 in the plasma of many HCV patients is enzymatically processed to produce a CXCL10 receptor antagonist. These findings introduce a role for chemokine antagonism during HCV infection and unveil new avenues for improved HCV diagnosis and therapy. PMID:21183783

  9. Autophagy Stimulation Abrogates Herpes simplex Virus-1 Infection

    PubMed Central

    Yakoub, Abraam M.; Shukla, Deepak

    2015-01-01

    Herpes simplex virus-1 (HSV-1) is a double-stranded DNA virus that causes life-long infections. HSV-1 infections may lead to herpetic stromal keratitis that may advance to corneal blindness. HSV-1 infections can also cause fatal conditions, such as herpes encephalitis, or neonatal disease. A major virulence mechanism of HSV-1 is the control of autophagy, an innate immune defense strategy that could otherwise degrade viral particles. Here, to investigate a new mechanism for antiviral therapy, we tested the effect of various autophagy inducers (physiological and pharmacological) on infection. Autophagy stimulation was confirmed to significantly suppress HSV-1 infection in various cell types, without affecting cell viability. This study establishes the importance of autophagy for regulating HSV-1 infection, and provides a proof-of-principle evidence for a novel antiviral mechanism. PMID:25856282

  10. Virus enrichment for single virus infection by using 3D insulator based dielectrophoresis.

    PubMed

    Masuda, Taisuke; Maruyama, Hisataka; Honda, Ayae; Arai, Fumihito

    2014-01-01

    We developed an active virus filter (AVF) that enables virus enrichment for single virus infection, by using insulator-based dielectrophoresis (iDEP). A 3D-constricted flow channel design enabled the production of an iDEP force in the microfluidic chip. iDEP using a chip with multiple active virus filters (AVFs) was more accurate and faster than using a chip with a single AVF, and improved the efficiency of virus trapping. We utilized maskless photolithography to achieve the precise 3D gray-scale exposure required for fabrication of constricted flow channel. Influenza virus (A PR/8) was enriched by a negative DEP force when sinusoidal wave was applied to the electrodes within an amplitude range of 20 Vp-p and a frequency of 10 MHz. AVF-mediated virus enrichment can be repeated simply by turning the current ON or OFF. Furthermore, the negative AVF can inhibit virus adhesion onto the glass substrate. We then trapped and transported one of the enriched viruses by using optical tweezers. This microfluidic chip facilitated the effective transport of a single virus from AVFs towards the cell-containing chamber without crossing an electrode. We successfully transported the virus to the cell chamber (v = 10 µm/s) and brought it infected with a selected single H292 cell. PMID:24918921

  11. Interleukin-3 protects mice from acute herpes simplex virus infection.

    PubMed Central

    Chan, W L; Ziltener, H J; Liew, F Y

    1990-01-01

    Evidence presented here from kinetic studies of interleukin-3 (IL-3) production by spleen cells from adult mice infected subcutaneously with HSV-1 and stimulated with virus antigen in vitro shows that high levels of IL-3 were produced at the onset of the animal's recovery from the disease state. Injections of anti-IL-3 antibody into HSV-1-infected mice resulted in exacerbation of the disease. Primary mouse embryonic head cells grown in the presence of murine IL-3, when infected with HSV-1, showed a 1000-fold decrease in virus titre compared with untreated control cells. This inhibiting effect was reversed by anti-IL-3 and anti-IFN-alpha, beta and gamma antibodies. These data suggest that IL-3 plays a host-protective role against HSV infection and it does so probably by inducing brain cells to produce interferons which then inhibit virus replication. PMID:2176641

  12. Immunofluorescence studies of disseminated Hantaan virus infection of suckling mice.

    PubMed Central

    Kurata, T; Tsai, T F; Bauer, S P; McCormick, J B

    1983-01-01

    Hantaan virus, the etiological agent of Korean hemorrhagic fever, was inoculated intracerebrally or intraperitoneally into suckling mice, and the course of the infection was followed by infectivity titration and immunofluorescence studies. Mice became ill and were moribund by 13 to 14 days postinfection. In mice inoculated either intracerebrally or intraperitoneally, virus antigen was present in brain, heart, lungs, liver, and kidney. Less consistently, specific fluorescence was observed in spleen, pituitary gland, thymus, lymph nodes, adrenal, pancreas, salivary glands, trigeminal ganglia, adipose tissue, intestine, and muscle. In all of these tissues, the primary target of infection was the capillary endothelium. In mice inoculated intracerebrally, virus antigen was present mainly in choroid plexus, hippocampal nuclei, and meninges, but in mice inoculated intraperitoneally, central nervous system infection was marked by antigen accumulation in cortical nuclei and thalamus. Images PMID:6134678

  13. Domestic Pigs Are Susceptible to Infection with Influenza B Viruses

    PubMed Central

    Ran, Zhiguang; Shen, Huigang; Lang, Yuekun; Kolb, Elizabeth A.; Turan, Nuri; Zhu, Laihua; Ma, Jingjiao; Bawa, Bhupinder; Liu, Qinfang; Liu, Haixia; Quast, Megan; Sexton, Gabriel; Krammer, Florian; Hause, Ben M.; Christopher-Hennings, Jane; Nelson, Eric A.; Richt, Juergen

    2015-01-01

    ABSTRACT Influenza B virus (IBV) causes seasonal epidemics in humans. Although IBV has been isolated from seals, humans are considered the primary host and reservoir of this important pathogen. It is unclear whether other animal species can support the replication of IBV and serve as a reservoir. Swine are naturally infected with both influenza A and C viruses. To determine the susceptibility of pigs to IBV infection, we conducted a serological survey for U.S. Midwest domestic swine herds from 2010 to 2012. Results of this study showed that antibodies to IBVs were detected in 38.5% (20/52) of sampled farms, and 7.3% (41/560) of tested swine serum samples were positive for IBV antibodies. Furthermore, swine herds infected with porcine reproductive and respiratory syndrome virus (PRRSV) showed a higher prevalence of IBV antibodies in our 2014 survey. In addition, IBV was detected in 3 nasal swabs collected from PRRSV-seropositive pigs by real-time RT-PCR and sequencing. Finally, an experimental infection in pigs, via intranasal and intratracheal routes, was performed using one representative virus from each of the two genetically and antigenically distinct lineages of IBVs: B/Brisbane/60/2008 (Victoria lineage) and B/Yamagata/16/1988 (Yamagata lineage). Pigs developed influenza-like symptoms and lung lesions, and they seroconverted after virus inoculation. Pigs infected with B/Brisbane/60/2008 virus successfully transmitted the virus to sentinel animals. Taken together, our data demonstrate that pigs are susceptible to IBV infection; therefore, they warrant further surveillance and investigation of swine as a potential host for human IBV. IMPORTANCE IBV is an important human pathogen, but its ability to infect other species, for example, pigs, is not well understood. We showed serological evidence that antibodies to two genetically and antigenically distinct lineages of IBVs were present among domestic pigs, especially in swine herds previously infected with PRRSV

  14. Multiple Epstein-Barr virus infections in healthy individuals

    NASA Technical Reports Server (NTRS)

    Walling, Dennis M.; Brown, Abigail L.; Etienne, Wiguins; Keitel, Wendy A.; Ling, Paul D.; Butel, J. S. (Principal Investigator)

    2003-01-01

    We employed a newly developed genotyping technique with direct representational detection of LMP-1 gene sequences to study the molecular epidemiology of Epstein-Barr virus (EBV) infection in healthy individuals. Infections with up to five different EBV genotypes were found in two of nine individuals studied. These results support the hypothesis that multiple EBV infections of healthy individuals are common. The implications for the development of an EBV vaccine are discussed.

  15. Vaccination of chimpanzees against infection by the hepatitis C virus.

    PubMed Central

    Choo, Q L; Kuo, G; Ralston, R; Weiner, A; Chien, D; Van Nest, G; Han, J; Berger, K; Thudium, K; Kuo, C

    1994-01-01

    A high incidence of community-acquired hepatitis C virus infection that can lead to the progressive development of chronic active hepatitis, liver cirrhosis, and primary hepatocellular carcinoma occurs throughout the world. A vaccine to control the spread of this agent that represents a major cause of chronic liver disease is therefore needed. Seven chimpanzees (Pan troglodytes) have been immunized with both putative envelope glycoproteins [E1 (gp33) and E2 (gp72)] that were copurified from HeLa cells infected with a recombinant vaccinia virus expression vector. Despite the induction of a weak humoral immune response to these viral glycoproteins in experimentally infected chimpanzees, a strong humoral immune response was obtained in all vaccines. The five highest responders showed complete protection against an i.v. challenge with homologous hepatitis C virus 1. The remaining two vaccines became infected, but both infection and disease may have been ameliorated in comparison with four similarly challenged control chimpanzees, all of which developed acute hepatitis and chronic infections. These results provide considerable encouragement for the eventual control of hepatitis C virus infection by vaccination. PMID:7509068

  16. Vaccination of chimpanzees against infection by the hepatitis C virus.

    PubMed

    Choo, Q L; Kuo, G; Ralston, R; Weiner, A; Chien, D; Van Nest, G; Han, J; Berger, K; Thudium, K; Kuo, C

    1994-02-15

    A high incidence of community-acquired hepatitis C virus infection that can lead to the progressive development of chronic active hepatitis, liver cirrhosis, and primary hepatocellular carcinoma occurs throughout the world. A vaccine to control the spread of this agent that represents a major cause of chronic liver disease is therefore needed. Seven chimpanzees (Pan troglodytes) have been immunized with both putative envelope glycoproteins [E1 (gp33) and E2 (gp72)] that were copurified from HeLa cells infected with a recombinant vaccinia virus expression vector. Despite the induction of a weak humoral immune response to these viral glycoproteins in experimentally infected chimpanzees, a strong humoral immune response was obtained in all vaccines. The five highest responders showed complete protection against an i.v. challenge with homologous hepatitis C virus 1. The remaining two vaccines became infected, but both infection and disease may have been ameliorated in comparison with four similarly challenged control chimpanzees, all of which developed acute hepatitis and chronic infections. These results provide considerable encouragement for the eventual control of hepatitis C virus infection by vaccination. PMID:7509068

  17. Why Zika virus infection has become a public health concern?

    PubMed

    Chen, Hui-Lan; Tang, Ren-Bin

    2016-04-01

    Prior to 2015, Zika Virus (ZIKV) outbreaks had occurred in areas of Africa, Southeast Asia, and the Pacific Islands. Although a causal relationship between Zika infection during pregnancy and microcephaly is strongly suspected, such a connection has not yet been scientifically proven. In May 2015, the outbreak of ZIKV infection in Brazil led to reports of syndrome and pregnant women giving birth to babies with birth defects and poor pregnancy outcomes; the Pan American Health Organization (PAHO) issued an alert regarding the first confirmed ZIKV infection in Brazil. Currently, ZIKV outbreaks are ongoing and it will be difficult to predict how the virus will spread over time. ZIKV is transmitted to humans primarily through the bite of infected mosquitos, Aedes aegypti and Aedes albopictus. These mosquitoes are the principle vectors of dengue, and ZIKV disease generally is reported to include symptoms associated with acute febrile illnesses that clinically resembles dengue fever. The laboratory diagnosis can be performed by using reverse-transcriptase polymerase chain reaction (RT-PCR) on serum, viral nucleic acid and virus-specific immunoglobulin M. There is currently no vaccine and antiviral treatment available for ZIKV infection, and the only way to prevent congenital ZIKV infection is to prevent maternal infection. In February 2016, the Taiwan Centers for Disease Control (Taiwan CDC) activated ZIKV as a Category V Notifiable Infectious Disease similar to Ebola virus disease and MERS. PMID:27052792

  18. Metabolic stress in infected cells may represent a therapeutic target for human immunodeficiency virus infection.

    PubMed

    Alonso-Villaverde, Carlos; Menéndez, Javier A; Joven, Jorge

    2013-07-01

    Worldwide, there are thousands of new cases of human immunodeficiency virus-1 (HIV-1) infection per day. The effectiveness of current combination antiretroviral therapy (ART) is relative; to prioritize finding vaccines and/or cure-oriented initiatives should be reinforced because there is little room, if any, for procrastination. Basic and clinical findings on HIV-1 reservoirs suggest that disruption of virus latency is feasible. Because the goal is curing HIV-1 infection, we should be aware that the challenge is to eradicate the viruses of every single infected cell and consequently acting upon virus latency is necessary but not sufficient. The large majority of the virus reservoir, CD4(+) T lymphocytes, is readily accessible but other minor reservoirs, where ART does not diffuse, require innovative strategies. The situation closely resembles that currently faced in the treatment of cancer. Exploiting the fact that histone deacetylase inhibitors, mainly vorinostat, may disrupt the latency of HIV-1, we propose to supplement this effect with a programmed interference in the metabolic stress of infected cells. Metformin and chloroquine are cheap and accessible modulators of pro-survival mechanisms to which viruses are constantly confronted to generate alternative energy sources and maximize virus production. Metformin restrains the use of the usurped cellular biosynthetic machinery by viral genes and chloroquine contributes to death of infected cells. We suggest that the combination of vorinostat, chloroquine and metformin should be combined with ART to pursue viral eradication in infected cells. PMID:23639282

  19. Diversity of Viruses Infecting the Green Microalga Ostreococcus lucimarinus

    PubMed Central

    Derelle, Evelyne; Monier, Adam; Cooke, Richard; Worden, Alexandra Z.

    2015-01-01

    ABSTRACT The functional diversity of eukaryotic viruses infecting a single host strain from seawater samples originating from distant marine locations is unknown. To estimate this diversity, we used lysis plaque assays to detect viruses that infect the widespread species Ostreococcus lucimarinus, which is found in coastal and mesotrophic systems, and O. tauri, which was isolated from coastal and lagoon sites from the northwest Mediterranean Sea. Detection of viral lytic activities against O. tauri was not observed using seawater from most sites, except those close to the area where the host strain was isolated. In contrast, the more cosmopolitan O. lucimarinus species recovered viruses from locations in the Atlantic and Pacific Oceans and the Mediterranean Sea. Six new O. lucimarinus viruses (OlVs) then were characterized and their genomes sequenced. Two subgroups of OlVs were distinguished based on their genetic distances and on the inversion of a central 32-kb-long DNA fragment, but overall their genomes displayed a high level of synteny. The two groups did not correspond to proximity of isolation sites, and the phylogenetic distance between these subgroups was higher than the distances observed among viruses infecting O. tauri. Our study demonstrates that viruses originating from very distant sites are able to infect the same algal host strain and can be more diverse than those infecting different species of the same genus. Finally, distinctive features and evolutionary distances between these different viral subgroups does not appear to be linked to biogeography of the viral isolates. IMPORTANCE Marine eukaryotic phytoplankton virus diversity has yet to be addressed, and more specifically, it is unclear whether diversity is connected to geographical distance and whether differential infection and lysis patterns exist among such viruses that infect the same host strain. Here, we assessed the genetic distance of geographically segregated viruses that infect the

  20. Viruses infecting Passiflora species in Florida

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This report documents multiple viruses in Passiflora spp. in Florida. It also reiterates the risk of movement of vegetatively-propagated plant material. This report provides an overview of this virus for growers, extension workers, crop consultants and research and regulatory scientists....

  1. Characterisation of three novel giant viruses reveals huge diversity among viruses infecting Prymnesiales (Haptophyta).

    PubMed

    Johannessen, Torill Vik; Bratbak, Gunnar; Larsen, Aud; Ogata, Hiroyuki; Egge, Elianne S; Edvardsen, Bente; Eikrem, Wenche; Sandaa, Ruth-Anne

    2015-02-01

    We have isolated three novel lytic dsDNA-viruses from Raunefjorden (Norway) that are putative members of the Mimiviridae family, namely Haptolina ericina virus RF02 (HeV RF02), Prymnesium kappa virus RF01 (PkV RF01), and Prymnesium kappa virus RF02 (PkV RF02). Each of the novel haptophyte viruses challenges the common conceptions of algal viruses with respect to host range, phylogenetic affiliation and size. PkV RF01 has a capsid of ~310 nm and is the largest algal virus particle ever reported while PkV RF01 and HeV RF02 were able to infect different species, even belonging to different genera. Moreover, PkV RF01 and HeV RF02 infected the same hosts, but phylogenetic analysis placed them in different groups. Our results reveal large variation among viruses infecting closely related microalgae, and challenge the common conception that algal viruses have narrow host range, and phylogeny reflecting their host affiliation. PMID:25546253

  2. Neuraminidase inhibitors for influenza B virus infection: efficacy and resistance

    PubMed Central

    Burnham, Andrew J.; Baranovich, Tatiana; Govorkova, Elena A.

    2013-01-01

    Many aspects of the biology and epidemiology of influenza B viruses are far less studied than for influenza A viruses, and one of these aspects is effectiveness and resistance to the clinically available antiviral drugs, the neuraminidase (NA) inhibitors (NAIs). Acute respiratory infections are one of the leading causes of death in children and adults, and influenza is among the few respiratory infections that can be prevented and treated by vaccination and antiviral treatment. Recent data has suggested that influenza B virus infections are of specific concern to pediatric patients because of the increased risk of severe disease. Treatment of influenza B is a challenging task for the following reasons: NAIs (e.g., oseltamivir and zanamivir) are the only FDA-approved class of antivirals available for treatment;the data suggest that oseltamivir is less effective than zanamivir in pediatric patients;zanamivir is not prescribed to patients younger than 7;influenza B viruses are less susceptible than influenza A viruses to NAIs in vitro;although the level of resistance to NAIs is low, the number of different molecular markers of resistance is higher than for influenza A viruses, and they are not well defined;the relationship between levels of NAI phenotypic resistance and known molecular markers, frequency of emergence, transmissibility, and fitness of NAI-resistant variants are not well established. This review presents current knowledge of the effectiveness of NAIs for influenza B virus and antiviral resistance in clinical, surveillance, and experimental studies. PMID:24013000

  3. Infection of cells by Sindbis virus at low temperature

    SciTech Connect

    Wang Gongbo; Hernandez, Raquel; Weninger, Keith; Brown, Dennis T. . E-mail: dennis_brown@ncsu.edu

    2007-06-05

    Sindbis virus, which belongs to the family Togaviridae genus Alphavirus infects a variety of vertebrate and invertebrate cells. The initial steps of Sindbis virus infection involve attachment, penetration and uncoating. Two different pathways of infection have been proposed for Alphaviruses. One proposed mechanism involves receptor mediated virion endocytosis followed by membrane fusion triggered by endosome acidification. This virus-host membrane fusion model, well established by influenza virus, has been applied to other unrelated membrane-containing viruses including Alphaviruses. The other mechanism proposes direct penetration of the cell plasma membrane by the virus glycoproteins in the absence of membrane fusion. This alternate model is supported by both ultrastructural [Paredes, A.M., Ferreira, D., Horton, M., Saad, A., Tsuruta, H., Johnston, R., Klimstra, W., Ryman, K., Hernandez, R., Chiu, W., Brown, D.T., 2004. Conformational changes in Sindbis virions resulting from exposure to low pH and interactions with cells suggest that cell penetration may occur at the cell surface in the absence of membrane fusion. Virology 324(2), 373-386] and biochemical [Koschinski, A., Wengler, G., Wengler, G., and Repp, H., 2005. Rare earth ions block the ion pores generated by the class II fusion proteins of alphaviruses and allow analysis of the biological functions of these pores. J. Gen. Virol. 86(Pt. 12), 3311-3320] studies. We have examined the ability of Sindbis virus to infect Baby Hamster Kidney (BHK) cells at temperatures which block endocytosis. We have found that under these conditions Sindbis virus infects cells in a temperature- and time-dependent fashion.

  4. Infection of cells by Sindbis virus at low temperature.

    PubMed

    Wang, Gongbo; Hernandez, Raquel; Weninger, Keith; Brown, Dennis T

    2007-06-01

    Sindbis virus, which belongs to the family Togaviridae genus Alphavirus infects a variety of vertebrate and invertebrate cells. The initial steps of Sindbis virus infection involve attachment, penetration and uncoating. Two different pathways of infection have been proposed for Alphaviruses. One proposed mechanism involves receptor mediated virion endocytosis followed by membrane fusion triggered by endosome acidification. This virus-host membrane fusion model, well established by influenza virus, has been applied to other unrelated membrane-containing viruses including Alphaviruses. The other mechanism proposes direct penetration of the cell plasma membrane by the virus glycoproteins in the absence of membrane fusion. This alternate model is supported by both ultrastructural [Paredes, A.M., Ferreira, D., Horton, M., Saad, A., Tsuruta, H., Johnston, R., Klimstra, W., Ryman, K., Hernandez, R., Chiu, W., Brown, D.T., 2004. Conformational changes in Sindbis virions resulting from exposure to low pH and interactions with cells suggest that cell penetration may occur at the cell surface in the absence of membrane fusion. Virology 324(2), 373-386] and biochemical [Koschinski, A., Wengler, G., Wengler, G., and Repp, H., 2005. Rare earth ions block the ion pores generated by the class II fusion proteins of alphaviruses and allow analysis of the biological functions of these pores. J. Gen. Virol. 86(Pt. 12), 3311-3320] studies. We have examined the ability of Sindbis virus to infect Baby Hamster Kidney (BHK) cells at temperatures which block endocytosis. We have found that under these conditions Sindbis virus infects cells in a temperature- and time-dependent fashion. PMID:17289103

  5. Avian Influenza A Viruses: Evolution and Zoonotic Infection.

    PubMed

    Kim, Se Mi; Kim, Young-Il; Pascua, Philippe Noriel Q; Choi, Young Ki

    2016-08-01

    Although efficient human-to-human transmission of avian influenza virus has yet to be seen, in the past two decades avian-to-human transmission of influenza A viruses has been reported. Influenza A/H5N1, in particular, has repeatedly caused human infections associated with high mortality, and since 1998 the virus has evolved into many clades of variants with significant antigenic diversity. In 2013, three (A/H7N9, A/H6N1, and A/H10N8) novel avian influenza viruses (AIVs) breached the animal-human host species barrier in Asia. In humans, roughly 35% of A/H7N9-infected patients succumbed to the zoonotic infection, and two of three A/H10N8 human infections were also lethal; however, neither of these viruses cause influenza-like symptoms in poultry. While most of these cases were associated with direct contact with infected poultry, some involved sustained human-to-human transmission. Thus, these events elicited concern regarding potential AIV pandemics. This article reviews the human incursions associated with AIV variants and the potential role of pigs as an intermediate host that may hasten AIV evolution. In addition, we discuss the known influenza A virus virulence and transmission factors and their evaluation in animal models. With the growing number of human AIV infections, constant vigilance for the emergence of novel viruses is of utmost importance. In addition, careful characterization and pathobiological assessment of these novel variants will help to identify strains of particular concern for future pandemics. PMID:27486732

  6. Hepatitis E Virus Infection among Solid Organ Transplant Recipients, the Netherlands

    PubMed Central

    Pas, Suzan D.; de Man, Rob A.; Mulders, Claudia; Balk, Aggie H.M.M.; van Hal, Peter T.W.; Weimar, Willem; Koopmans, Marion P.G.; Osterhaus, Albert D.M.E.

    2012-01-01

    We screened 1,200 living heart, lung, liver, and kidney transplant recipients for hepatitis E virus infection by reverse transcription PCR. In 12 (1%) patients, hepatitis E virus infection was identified; in 11 patients, chronic infection developed. This immunocompromised population is at risk for hepatitis E virus infection. PMID:22516170

  7. Pathogenesis of Lassa Fever Virus Infection: I. Susceptibility of Mice to Recombinant Lassa Gp/LCMV Chimeric Virus

    PubMed Central

    Lee, Andrew M.; Cruite, Justin; Welch, Megan J.; Sullivan, Brian; Oldstone, Michael B.A.

    2013-01-01

    Lassa virus (LASV) is a BSL-4 restricted agent. To allow study of infection by LASV under BSL-2 conditions, we generated a recombinant virus in which the LASV glycoprotein (Gp) was placed on the backbone of lymphocytic choriomeningitis virus (LCMV) Cl13 nucleoprotein, Z and polymerase genes (rLCMV Cl13/LASV Gp). The recombinant virus displayed high tropism for dendritic cells following in vitro or in vivo infection. Inoculation of immunocompetent adults resulted in an acute infection, generation of virus-specific CD8+ T cells and clearance of the infection. Inoculation of newborn mice with rLCMV Cl13/LASV Gp resulted in a life-long persistent infection. Interestingly, adoptive transfer of rLCMV Cl13/LASV Gp immune memory cells into such persistently infected mice failed to purge virus but, in contrast, cleared virus from mice persistently infected with wt LCMV Cl13. PMID:23684417

  8. Pathogenesis of Lassa fever virus infection: I. Susceptibility of mice to recombinant Lassa Gp/LCMV chimeric virus.

    PubMed

    Lee, Andrew M; Cruite, Justin; Welch, Megan J; Sullivan, Brian; Oldstone, Michael B A

    2013-08-01

    Lassa virus (LASV) is a BSL-4 restricted agent. To allow study of infection by LASV under BSL-2 conditions, we generated a recombinant virus in which the LASV glycoprotein (Gp) was placed on the backbone of lymphocytic choriomeningitis virus (LCMV) Cl13 nucleoprotein, Z and polymerase genes (rLCMV Cl13/LASV Gp). The recombinant virus displayed high tropism for dendritic cells following in vitro or in vivo infection. Inoculation of immunocompetent adults resulted in an acute infection, generation of virus-specific CD8(+) T cells and clearance of the infection. Inoculation of newborn mice with rLCMV Cl13/LASV Gp resulted in a life-long persistent infection. Interestingly, adoptive transfer of rLCMV Cl13/LASV Gp immune memory cells into such persistently infected mice failed to purge virus but, in contrast, cleared virus from mice persistently infected with wt LCMV Cl13. PMID:23684417

  9. Pseudorabies Virus Infection Alters Neuronal Activity and Connectivity In Vitro

    PubMed Central

    McCarthy, Kelly M.; Tank, David W.; Enquist, Lynn W.

    2009-01-01

    Alpha-herpesviruses, including human herpes simplex virus 1 & 2, varicella zoster virus and the swine pseudorabies virus (PRV), infect the peripheral nervous system of their hosts. Symptoms of infection often include itching, numbness, or pain indicative of altered neurological function. To determine if there is an in vitro electrophysiological correlate to these characteristic in vivo symptoms, we infected cultured rat sympathetic neurons with well-characterized strains of PRV known to produce virulent or attenuated symptoms in animals. Whole-cell patch clamp recordings were made at various times after infection. By 8 hours of infection with virulent PRV, action potential (AP) firing rates increased substantially and were accompanied by hyperpolarized resting membrane potentials and spikelet-like events. Coincident with the increase in AP firing rate, adjacent neurons exhibited coupled firing events, first with AP-spikelets and later with near identical resting membrane potentials and AP firing. Small fusion pores between adjacent cell bodies formed early after infection as demonstrated by transfer of the low molecular weight dye, Lucifer Yellow. Later, larger pores formed as demonstrated by transfer of high molecular weight Texas red-dextran conjugates between infected cells. Further evidence for viral-induced fusion pores was obtained by infecting neurons with a viral mutant defective for glycoprotein B, a component of the viral membrane fusion complex. These infected neurons were essentially identical to mock infected neurons: no increased AP firing, no spikelet-like events, and no electrical or dye transfer. Infection with PRV Bartha, an attenuated circuit-tracing strain delayed, but did not eliminate the increased neuronal activity and coupling events. We suggest that formation of fusion pores between infected neurons results in electrical coupling and elevated firing rates, and that these processes may contribute to the altered neural function seen in PRV-infected

  10. Suppression of influenza virus infection by the orf virus isolated in Taiwan

    PubMed Central

    LIN, Fong-Yuan; TSENG, Yeu-Yang; CHAN, Kun-Wei; KUO, Shu-Ting; YANG, Cheng-Hsiung; WANG, Chi-Young; TAKASU, Masaki; HSU, Wei-Li; WONG, Min-Liang

    2015-01-01

    Orf virus (ORFV), a member of parapoxvirus, is an enveloped virus with genome of double-stranded DNA. ORFV causes contagious pustular dermatitis or contagious ecthyma in sheep and goats worldwide. In general, detection of viral DNA and observing ORFV virion in tissues of afflicted animals are two methods commonly used for diagnosis of orf infection; however, isolation of the ORFV in cell culture using virus-containing tissue as inoculum is known to be difficult. In this work, the ORFV (Hoping strain) isolated in central Taiwan was successfully grown in cell culture. We further examined the biochemical characteristic of our isolate, including viral genotyping, viral mRNA and protein expression. By electron microscopy, one unique form of viral particle from ORFV infected cellular lysate was demonstrated in the negative-stained field. Moreover, immunomodulating and anti-influenza virus properties of this ORFV were investigated. ORFV stimulated human monocytes (THP-1) secreting proinflammatory cytokines IL-8 and TNF-α. And, pre-treatment of ORFV-infected cell medium prevents A549 cells from subsequent type A influenza virus (IAV) infection. Similarly, mice infected with ORFV via both intramuscular and subcutaneous routes at two days prior to IAV infection significantly decreased the replication of IAV. In summary, the results of a current study indicated our Hoping strain harbors the immune modulator property; with such a bio-adjuvanticity, we further proved that pre-exposure of ORFV protects animals from subsequent IAV infection. PMID:25855509

  11. Eastern Equine Encephalomyelitis Virus Infection in a Horse from California

    PubMed Central

    Kinde, Hailu; Jay, Michele T.; Kramer, Laura D.; Green, Emily-Gene N.; Chiles, Robert E.; Ostlund, Eileen; Husted, Stan; Smith, Jonathan; Parker, Michael D.

    2002-01-01

    A yearling quarter horse, which was raised in southern California, received routine vaccinations for prevention of infection by Eastern equine encephalomyelitis virus (EEEV). One week later, severe neurologic signs developed, and the horse was humanely destroyed because vaccine-related encephalomyelitis was suspected. A final diagnosis of EEEV infection was established on the basis of acute onset of the neurologic signs, histopathologic and serologic testing, and isolation and molecular characterization of EEEV from brain tissue. The vaccine was extensively tested for viral inactivation. Nucleotide sequences from the vaccine and the virus isolated in the affected horse were also compared. In California, arboviral encephalomyelitides are rarely reported, and EEEV infection has not previously been documented. This report describes the occurrence of EEEV infection in the horse and the investigation to determine the source of infection, which was not definitively identified. PMID:11927026

  12. Quantitation of Productively Infected Monocytes and Macrophages of Simian Immunodeficiency Virus-Infected Macaques

    PubMed Central

    Avalos, Claudia R.; Price, Sarah L.; Forsyth, Ellen R.; Pin, Julia N.; Shirk, Erin N.; Bullock, Brandon T.; Queen, Suzanne E.; Li, Ming; Gellerup, Dane; O'Connor, Shelby L.; Zink, M. Christine; Mankowski, Joseph L.; Gama, Lucio

    2016-01-01

    ABSTRACT Despite the success of combined antiretroviral therapy (ART), human immunodeficiency virus (HIV) infection remains a lifelong infection because of latent viral reservoirs in infected patients. The contribution of CD4+ T cells to infection and disease progression has been extensively studied. However, during early HIV infection, macrophages in brain and other tissues are infected and contribute to tissue-specific diseases, such as encephalitis and dementia in brain and pneumonia in lung. The extent of infection of monocytes and macrophages has not been rigorously assessed with assays comparable to those used to study infection of CD4+ T cells and to evaluate the number of CD4+ T cells that harbor infectious viral genomes. To assess the contribution of productively infected monocytes and macrophages to HIV- and simian immunodeficiency virus (SIV)-infected cells in vivo, we developed a quantitative virus outgrowth assay (QVOA) based on similar assays used to quantitate CD4+ T cell latent reservoirs in HIV- and SIV-infected individuals in whom the infection is suppressed by ART. Myeloid cells expressing CD11b were serially diluted and cocultured with susceptible cells to amplify virus. T cell receptor β RNA was measured as a control to assess the potential contribution of CD4+ T cells in the assay. Virus production in the supernatant was quantitated by quantitative reverse transcription-PCR. Productively infected myeloid cells were detected in blood, bronchoalveolar lavage fluid, lungs, spleen, and brain, demonstrating that these cells persist throughout SIV infection and have the potential to contribute to the viral reservoir during ART. IMPORTANCE Infection of CD4+ T cells and their role as latent reservoirs have been rigorously assessed; however, the frequency of productively infected monocytes and macrophages in vivo has not been similarly studied. Myeloid cells, unlike lymphocytes, are resistant to the cytopathic effects of HIV. Moreover, tissue

  13. Occult hepatitis B virus infection among Mexican human immunodeficiency virus-1-infected patients

    PubMed Central

    Alvarez-Muñoz, Ma Teresa; Maldonado-Rodriguez, Angelica; Rojas-Montes, Othon; Torres-Ibarra, Rocio; Gutierrez-Escolano, Fernanda; Vazquez-Rosales, Guillermo; Gomez, Alejandro; Muñoz, Onofre; Torres, Javier; Lira, Rosalia

    2014-01-01

    AIM: To determine the frequency of occult hepatitis B infection (OHBI) in a group of human immunodeficiency virus (HIV)-1+/ hepatitis B surface antigen negative (HBsAg)- patients from Mexico. METHODS: We investigated the presence of OHBI in 49 HIV-1+/HBsAg- patients. Hepatitis B virus (HBV) DNA was analyzed using nested PCR to amplify the Core (C) region and by real-time PCR to amplify a region of the S and X genes. The possible associations between the variables and OHBI were investigated using Pearson’s χ2 and/or Fisher’s exact test. RESULTS: We found that the frequency of OHBI was 49% among the group of 49 HIV-1+/HBsAg- patients studied. The presence of OHBI was significantly associated with the HIV-1 RNA viral load [odds ratio (OR) = 8.75; P = 0.001; 95%CI: 2.26-33.79] and with HIV-antiretroviral treatment with drugs that interfere with HBV replication (lamivudine, tenofovir or emtricitabine) (OR = 0.25; P = 0.05; 95%CI: 0.08-1.05). CONCLUSION: The OHBI frequency is high among 49 Mexican HIV-1+/HBsAg- patients and it was more frequent in patients with detectable HIV RNA, and less frequent in patients who are undergoing HIV-ARV treatment with drugs active against HBV. PMID:25309083

  14. Zika virus infections: An overview of current scenario.

    PubMed

    Dasti, Javid Iqbal

    2016-07-01

    Zika virus (ZIKV) was discovered more than half a century ago, recently it has gained unprecedented attention by the global health community. Until 2007, only 14 cases of human ZIKV infections were reported around the globe, while during the current outbreak, estimated cases mounted to approximately 1.5 million in Brazil alone, the virus was disseminated to wider South-American territories and travel-associated ZIKV infections were reported in USA, Europe and recently in China. ZIKV infections remain asymptomatic in approximately 80% of the individuals, and no anti-viral treatments were recommended. Yet, neurological complications associated with the infections, such as infant microcephaly and Guillain-Barré syndrome are major cause of the concern. Although, based on small numbers of cases, existing evidence strongly supports an exclusive link of viral infection and observed neurological complications. However, much work remains to assign exact numbers of complications caused by ZIKV. Regarding its structural attributes ZIKV shows remarkable resemblance with dengue virus and West-Nile virus. Despite, genomes of different ZIKV strains have already been decoded; role of the viral components in infection process and particularly pathogenesis of the disease remain widely unclear. In vulnerable areas, most viable strategy to ensure public health safety is vector control and enhanced public awareness about the transmission of the disease. PMID:27393087

  15. Innate immune targets of hepatitis B virus infection

    PubMed Central

    Zou, Zhi-Qiang; Wang, Li; Wang, Kai; Yu, Ji-Guang

    2016-01-01

    Approximately 400 million people are chronically infected with hepatitis B virus (HBV) globally despite the widespread immunization of HBV vaccine and the development of antiviral therapies. The immunopathogenesis of HBV infection is initiated and driven by complexed interactions between the host immune system and the virus. Host immune responses to viral particles and proteins are regarded as the main determinants of viral clearance or persistent infection and hepatocyte injury. Innate immune system is the first defending line of host preventing from virus invasion. It is acknowledged that HBV has developed active tactics to escape innate immune recognition or actively interfere with innate immune signaling pathways and induce immunosuppression, which favor their replication. HBV reduces the expression of pattern-recognition receptors in the innate immune cells in humans. Also, HBV may interrupt different parts of antiviral signaling pathways, leading to the reduced production of antiviral cytokines such as interferons that contribute to HBV immunopathogenesis. A full comprehension of the mechanisms as to how HBV inactivates various elements of the innate immune response to initiate and maintain a persistent infection can be helpful in designing new immunotherapeutic methods for preventing and eradicating the virus. In this review, we aimed to summarize different branches the innate immune targeted by HBV infection. The review paper provides evidence that multiple components of immune responses should be activated in combination with antiviral therapy to disrupt the tolerance to HBV for eliminating HBV infection. PMID:27330680

  16. Innate immune targets of hepatitis B virus infection.

    PubMed

    Zou, Zhi-Qiang; Wang, Li; Wang, Kai; Yu, Ji-Guang

    2016-06-18

    Approximately 400 million people are chronically infected with hepatitis B virus (HBV) globally despite the widespread immunization of HBV vaccine and the development of antiviral therapies. The immunopathogenesis of HBV infection is initiated and driven by complexed interactions between the host immune system and the virus. Host immune responses to viral particles and proteins are regarded as the main determinants of viral clearance or persistent infection and hepatocyte injury. Innate immune system is the first defending line of host preventing from virus invasion. It is acknowledged that HBV has developed active tactics to escape innate immune recognition or actively interfere with innate immune signaling pathways and induce immunosuppression, which favor their replication. HBV reduces the expression of pattern-recognition receptors in the innate immune cells in humans. Also, HBV may interrupt different parts of antiviral signaling pathways, leading to the reduced production of antiviral cytokines such as interferons that contribute to HBV immunopathogenesis. A full comprehension of the mechanisms as to how HBV inactivates various elements of the innate immune response to initiate and maintain a persistent infection can be helpful in designing new immunotherapeutic methods for preventing and eradicating the virus. In this review, we aimed to summarize different branches the innate immune targeted by HBV infection. The review paper provides evidence that multiple components of immune responses should be activated in combination with antiviral therapy to disrupt the tolerance to HBV for eliminating HBV infection. PMID:27330680

  17. Finding balance: Virus populations reach equilibrium during the infection process.

    PubMed

    Harper, S J; Cowell, S J; Dawson, W O

    2015-11-01

    Virus populations, mixtures of viral strains or species, are a common feature of viral infection, and influence many viral processes including infection, transmission, and the induction of disease. Yet, little is known of the rules that define the composition and structure of these populations. In this study, we used three distinct strains of Citrus tristeza virus (CTV) to examine the effect of inoculum composition, titer, and order, on the virus population. We found that CTV populations stabilized at the same equilibrium irrespective of how that population was introduced into a host. In addition, both field and experimental observations showed that these equilibria were relatively uniform between individual hosts of the same species and under the same conditions. We observed that the structure of the equilibria reached is determined primarily by the host, with the same inoculum reaching different equilibria in different species, and by the fitness of individual virus variants. PMID:26291064

  18. Neutralizing antibodies in Borna disease virus-infected rats.

    PubMed Central

    Hatalski, C G; Kliche, S; Stitz, L; Lipkin, W I

    1995-01-01

    Borna disease is a neurologic syndrome caused by infection with a nonsegmented, negative-strand RNA virus, Borna disease virus. Infected animals have antibodies to two soluble viral proteins, p40 and p23, and a membrane-associated viral glycoprotein, gp18. We examined the time course for the development of neutralization activity and the expression of antibodies to individual viral proteins in sera of infected rats. The appearance of neutralizing activity correlated with the development of immunoreactivity to gp18, but not p40 or p23. Monospecific and monoclonal antibodies to native gp18 and recombinant nonglycosylated gp18 were also found to have neutralizing activity and to immunoprecipitate viral particles or subparticles. These findings suggest that gp18 is likely to be present on the surface of the viral particles and is likely to contain epitopes important for virus neutralization. PMID:7815538

  19. Cohabitation reaction-diffusion model for virus focal infections

    NASA Astrophysics Data System (ADS)

    Amor, Daniel R.; Fort, Joaquim

    2014-12-01

    The propagation of virus infection fronts has been typically modeled using a set of classical (noncohabitation) reaction-diffusion equations for interacting species. However, for some single-species systems it has been recently shown that noncohabitation reaction-diffusion equations may lead to unrealistic descriptions. We argue that previous virus infection models also have this limitation, because they assume that a virion can simultaneously reproduce inside a cell and diffuse away from it. For this reason, we build a several-species cohabitation model that does not have this limitation. Furthermore, we perform a sensitivity analysis for the most relevant parameters of the model, and we compare the predicted infection speed with observed data for two different strains of the T7 virus.

  20. The First Imported Case Infected with Chikungunya Virus in Korea

    PubMed Central

    2015-01-01

    Chikungunya is caused by an arbovirus transmitted by Aedes mosquito vector. With the increase of habitat of mosquito by global warming and frequent international travel and interchange, chikungunya reemerged and showed global distribution recently. Until now there has not been reported any case infected with chikungunya virus in Korea. A 23-year-old man has been the Republic of the Philippines for 1 week, and visited our emergency center due to fever and back pain. Chikungunya viral infection was diagnosed by specific IgM for chickungunya virus by enzyme-linked immunosorbent assayin Korea Centers for Disease Control and Prevention. His clinical course was self limited. We introduce the first imported case infected with chikungunya virus in Korea. PMID:25844264

  1. Targeting Viral Proteostasis Limits Influenza Virus, HIV, and Dengue Virus Infection.

    PubMed

    Heaton, Nicholas S; Moshkina, Natasha; Fenouil, Romain; Gardner, Thomas J; Aguirre, Sebastian; Shah, Priya S; Zhao, Nan; Manganaro, Lara; Hultquist, Judd F; Noel, Justine; Sachs, David; Sachs, David H; Hamilton, Jennifer; Leon, Paul E; Chawdury, Amit; Tripathi, Shashank; Melegari, Camilla; Campisi, Laura; Hai, Rong; Metreveli, Giorgi; Gamarnik, Andrea V; García-Sastre, Adolfo; Greenbaum, Benjamin; Simon, Viviana; Fernandez-Sesma, Ana; Krogan, Nevan J; Mulder, Lubbertus C F; van Bakel, Harm; Tortorella, Domenico; Taunton, Jack; Palese, Peter; Marazzi, Ivan

    2016-01-19

    Viruses are obligate parasites and thus require the machinery of the host cell to replicate. Inhibition of host factors co-opted during active infection is a strategy hosts use to suppress viral replication and a potential pan-antiviral therapy. To define the cellular proteins and processes required for a virus during infection is thus crucial to understanding the mechanisms of virally induced disease. In this report, we generated fully infectious tagged influenza viruses and used infection-based proteomics to identify pivotal arms of cellular signaling required for influenza virus growth and infectivity. Using mathematical modeling and genetic and pharmacologic approaches, we revealed that modulation of Sec61-mediated cotranslational translocation selectively impaired glycoprotein proteostasis of influenza as well as HIV and dengue viruses and led to inhibition of viral growth and infectivity. Thus, by studying virus-human protein-protein interactions in the context of active replication, we have identified targetable host factors for broad-spectrum antiviral therapies. PMID:26789921

  2. Mitochondrial dysfunction in rabies virus infection of neurons.

    PubMed

    Alandijany, Thamir; Kammouni, Wafa; Roy Chowdhury, Subir K; Fernyhough, Paul; Jackson, Alan C

    2013-12-01

    Infection with the challenge virus standard-11 (CVS) strain of fixed rabies virus induces neuronal process degeneration in adult mice after hindlimb footpad inoculation. CVS-induced axonal swellings of primary rodent dorsal root ganglion neurons are associated with 4-hydroxy-2-nonenal protein adduct staining, indicating a critical role of oxidative stress. Mitochondrial dysfunction is the major cause of oxidative stress. We hypothesized that CVS infection induces mitochondrial dysfunction leading to oxidative stress. We investigated the effects of CVS infection on several mitochondrial parameters in different cell types. CVS infection significantly increased maximal uncoupled respiration and complex IV respiration and complex I and complex IV activities, but did not affect complex II-III or citrate synthase activities. Increases in complex I activity, but not complex IV activity, correlated with susceptibility of the cells to CVS infection. CVS infection maintained coupled respiration and rate of proton leak, indicating a tight mitochondrial coupling. Possibly as a result of enhanced complex activity and efficient coupling, a high mitochondrial membrane potential was generated. CVS infection reduced the intracellular ATP level and altered the cellular redox state as indicated by a high NADH/NAD+ ratio. The basal production of reactive oxygen species (ROS) was not affected in CVS-infected neurons. However, a higher rate of ROS generation occurred in CVS-infected neurons in the presence of mitochondrial substrates and inhibitors. We conclude that CVS infection induces mitochondrial dysfunction leading to ROS overgeneration and oxidative stress. PMID:24277436

  3. Background review for diagnostic test development for Zika virus infection

    PubMed Central

    Charrel, Rémi N; Leparc-Goffart, Isabelle; Pas, Suzan; de Lamballerie, Xavier; Koopmans, Marion; Reusken, Chantal

    2016-01-01

    Abstract Objective To review the state of knowledge about diagnostic testing for Zika virus infection and identify areas of research needed to address the current gaps in knowledge. Methods We made a non-systematic review of the published literature about Zika virus and supplemented this with information from commercial diagnostic test kits and personal communications with researchers in European preparedness networks. The review covered current knowledge about the geographical spread, pathogen characteristics, life cycle and infection kinetics of the virus. The available molecular and serological tests and biosafety issues are described and discussed in the context of the current outbreak strain. Findings We identified the following areas of research to address current knowledge gaps: (i) an urgent assessment of the laboratory capacity and capability of countries to detect Zika virus; (ii) rapid and extensive field validation of the available molecular and serological tests in areas with and without Zika virus transmission, with a focus on pregnant women; (iii) monitoring the genomic diversity of circulating Zika virus strains; (iv) prospective studies into the virus infection kinetics, focusing on diagnostic sampling (specimen types, combinations and timings); and (v) developing external quality assessments for molecular and serological testing, including differential diagnosis for similar viruses and symptom clusters. The availability of reagents for diagnostic development (virus strains and antigens, quantified viral ribonucleic acid) needs to be facilitated. Conclusion An international laboratory response is needed, including preparation of protocols for prospective studies to address the most pressing information needs. PMID:27516635

  4. Permissive and restricted virus infection of murine embryonic stem cells.

    PubMed

    Wash, Rachael; Calabressi, Sabrina; Franz, Stephanie; Griffiths, Samantha J; Goulding, David; Tan, E-Pien; Wise, Helen; Digard, Paul; Haas, Jürgen; Efstathiou, Stacey; Kellam, Paul

    2012-10-01

    Recent RNA interference (RNAi) studies have identified many host proteins that modulate virus infection, but small interfering RNA 'off-target' effects and the use of transformed cell lines limit their conclusiveness. As murine embryonic stem (mES) cells can be genetically modified and resources exist where many and eventually all known mouse genes are insertionally inactivated, it was reasoned that mES cells would provide a useful alternative to RNAi screens. Beyond allowing investigation of host-pathogen interactions in vitro, mES cells have the potential to differentiate into other primary cell types, as well as being used to generate knockout mice for in vivo studies. However, mES cells are poorly characterized for virus infection. To investigate whether ES cells can be used to explore host-virus interactions, this study characterized the responses of mES cells following infection by herpes simplex virus type 1 (HSV-1) and influenza A virus. HSV-1 replicated lytically in mES cells, although mES cells were less permissive than most other cell types tested. Influenza virus was able to enter mES cells and express some viral proteins, but the replication cycle was incomplete and no infectious virus was produced. Knockdown of the host protein AHCYL1 in mES cells reduced HSV-1 replication, showing the potential for using mES cells to study host-virus interactions. Transcriptional profiling, however, indicated the lack of an efficient innate immune response in these cells. mES cells may thus be useful to identify host proteins that play a role in virus replication, but they are not suitable to determine factors that are involved in innate host defence. PMID:22815272

  5. Permissive and restricted virus infection of murine embryonic stem cells

    PubMed Central

    Wash, Rachael; Calabressi, Sabrina; Franz, Stephanie; Griffiths, Samantha J.; Goulding, David; Tan, E-Pien; Wise, Helen; Digard, Paul; Haas, Jürgen; Efstathiou, Stacey

    2012-01-01

    Recent RNA interference (RNAi) studies have identified many host proteins that modulate virus infection, but small interfering RNA ‘off-target’ effects and the use of transformed cell lines limit their conclusiveness. As murine embryonic stem (mES) cells can be genetically modified and resources exist where many and eventually all known mouse genes are insertionally inactivated, it was reasoned that mES cells would provide a useful alternative to RNAi screens. Beyond allowing investigation of host–pathogen interactions in vitro, mES cells have the potential to differentiate into other primary cell types, as well as being used to generate knockout mice for in vivo studies. However, mES cells are poorly characterized for virus infection. To investigate whether ES cells can be used to explore host–virus interactions, this study characterized the responses of mES cells following infection by herpes simplex virus type 1 (HSV-1) and influenza A virus. HSV-1 replicated lytically in mES cells, although mES cells were less permissive than most other cell types tested. Influenza virus was able to enter mES cells and express some viral proteins, but the replication cycle was incomplete and no infectious virus was produced. Knockdown of the host protein AHCYL1 in mES cells reduced HSV-1 replication, showing the potential for using mES cells to study host–virus interactions. Transcriptional profiling, however, indicated the lack of an efficient innate immune response in these cells. mES cells may thus be useful to identify host proteins that play a role in virus replication, but they are not suitable to determine factors that are involved in innate host defence. PMID:22815272

  6. Seroepidemiology of Asymptomatic Dengue Virus Infection in Jeddah, Saudi Arabia

    PubMed Central

    Jamjoom, Ghazi A.; Azhar, Esam I.; Kao, Moujahid A.; Radadi, Raja M.

    2016-01-01

    BACKGROUND Although virologically confirmed dengue fever has been recognized in Jeddah, Saudi Arabia, since 1994, causing yearly outbreaks, no proper seroepidemiologic studies on dengue virus have been conducted in this region. Such studies can define the extent of infection by this virus and estimate the proportion that may result in disease. The aim of this study was to measure the seroprevalence of past dengue virus infection in healthy Saudi nationals from different areas in the city of Jeddah and to investigate demographic and environmental factors that may increase exposure to infection. METHODS Sera were collected from 1984 Saudi subjects attending primary health care centers in six districts of Jeddah. These included general patients of various ages seeking routine vaccinations, antenatal care or treatment of different illnesses excluding fever or suspected dengue. A number of blood donors were also tested. Serum samples were tested by enzyme immunoassay (EIA) for IgG antibodies to dengue viruses 1, 2, 3, 4. A questionnaire was completed for each patient recording various anthropometric data and factors that may indicate possible risk of exposure to mosquito bites and dengue infection. Patients with missing data and those who reported a history of dengue fever were excluded from analysis, resulting in a sample of 1939 patients to be analyzed. RESULTS The overall prevalence of dengue virus infection as measured by anti-dengue IgG antibodies from asymptomatic residents in Jeddah was 47.8% (927/1939) and 37% (68/184) in blood donors. Infection mostly did not result in recognizable disease, as only 19 of 1956 subjects with complete information (0.1%) reported having dengue fever in the past. Anti dengue seropositivity increased with age and was higher in males than females and in residents of communal housing and multistory buildings than in villas. One of the six districts showed significant increase in exposure rate as compared to the others. Availability of

  7. Japanese encephalitis virus tropism in experimentally infected pigs.

    PubMed

    Ricklin, Meret E; Garcìa-Nicolàs, Obdulio; Brechbühl, Daniel; Python, Sylvie; Zumkehr, Beatrice; Posthaus, Horst; Oevermann, Anna; Summerfield, Artur

    2016-01-01

    Pigs are considered to be the main amplifying host for Japanese encephalitis virus (JEV), and their infection can correlate with human cases of disease. Despite their importance in the ecology of the virus as it relates to human cases of encephalitis, the pathogenesis of JEV in pigs remains obscure. In the present study, the localization and kinetics of virus replication were investigated in various tissues after experimental intravenous infection of pigs. The data demonstrate a rapid and broad spreading of the virus to the central nervous system (CNS) and various other organs. A particular tropism of JEV in pigs not only to the CNS but also for secondary lymphoid tissue, in particular the tonsils with the overall highest viral loads, was observed. In this organ, even 11 days post infection, the latest time point of the experiment, no apparent decrease in viral RNA loads and live virus was found despite the presence of a neutralizing antibody response. This was also well beyond the clinical and viremic phase. These results are of significance for the pathogenesis of JEV, and call for further experimental studies focusing on the cellular source and duration of virus replication in pigs. PMID:26911997

  8. Possible Association Between Zika Virus Infection and Microcephaly - Brazil, 2015.

    PubMed

    Schuler-Faccini, Lavinia; Ribeiro, Erlane M; Feitosa, Ian M L; Horovitz, Dafne D G; Cavalcanti, Denise P; Pessoa, André; Doriqui, Maria Juliana R; Neri, Joao Ivanildo; Neto, Joao Monteiro de Pina; Wanderley, Hector Y C; Cernach, Mirlene; El-Husny, Antonette S; Pone, Marcos V S; Serao, Cassio L C; Sanseverino, Maria Teresa V

    2016-01-01

    In early 2015, an outbreak of Zika virus, a flavivirus transmitted by Aedes mosquitoes, was identified in northeast Brazil, an area where dengue virus was also circulating. By September, reports of an increase in the number of infants born with microcephaly in Zika virus-affected areas began to emerge, and Zika virus RNA was identified in the amniotic fluid of two women whose fetuses had been found to have microcephaly by prenatal ultrasound. The Brazil Ministry of Health (MoH) established a task force to investigate the possible association of microcephaly with Zika virus infection during pregnancy and a registry for incident microcephaly cases (head circumference ≥2 standard deviations [SD] below the mean for sex and gestational age at birth) and pregnancy outcomes among women suspected to have had Zika virus infection during pregnancy. Among a cohort of 35 infants with microcephaly born during August-October 2015 in eight of Brazil's 26 states and reported to the registry, the mothers of all 35 had lived in or visited Zika virus-affected areas during pregnancy, 25 (71%) infants had severe microcephaly (head circumference >3 SD below the mean for sex and gestational age), 17 (49%) had at least one neurologic abnormality, and among 27 infants who had neuroimaging studies, all had abnormalities. Tests for other congenital infections were negative. All infants had a lumbar puncture as part of the evaluation and cerebrospinal fluid (CSF) samples were sent to a reference laboratory in Brazil for Zika virus testing; results are not yet available. Further studies are needed to confirm the association of microcephaly with Zika virus infection during pregnancy and to understand any other adverse pregnancy outcomes associated with Zika virus infection. Pregnant women in Zika virus-affected areas should protect themselves from mosquito bites by using air conditioning, screens, or nets when indoors, wearing long sleeves and pants, using permethrin-treated clothing and gear

  9. Insights into human immunodeficiency virus-hepatitis B virus co-infection in India

    PubMed Central

    Chakravarty, Runu; Pal, Ananya

    2015-01-01

    Shared routes of transmission lead to frequent human immunodeficiency virus (HIV)-hepatitis B virus (HBV) co-infection in a host which results in about 10% of HIV positive individuals to have chronic hepatitis B infection worldwide. In post-antiretroviral therapy era, liver diseases have emerged as the leading cause of morbidity and mortality in HIV-infected individuals and HBV co-infection have become the major health issue among this population particularly from the regions with endemic HBV infection. In setting of HIV-HBV co-infection, HIV significantly impacts the natural history of HBV infection, its disease profile and the treatment outcome in negative manner. Moreover, the epidemiological pattern of HBV infection and the diversity in HBV genome (genotypic and phenotypic) are also varied in HIV co-infected subjects as compared to HBV mono-infected individuals. Several reports on the abovementioned issues are available from developed parts of the world as well as from sub-Saharan African countries. In contrast, most of these research areas remained unexplored in India despite having considerable burden of HIV and HBV infections. This review discusses present knowledge from the studies on HIV-HBV co-infection in India and relevant reports from different parts of the world. Issues needed for the future research relevant to HIV-HBV co-infection in India are also highlighted here, including a call for further investigations on this field of study. PMID:26279986

  10. First study of different insect cells to triatoma virus infection.

    PubMed

    Susevich, María Laura; Marti, Gerardo Aníbal; Metz, Germán Ernesto; Echeverría, María Gabriela

    2015-04-01

    The use of viruses for biological control is a new option to be considered. The family Dicistroviridae, which affects only invertebrates, is one of the families that have been proposed for this purpose. The Triatoma virus (TrV), a member of this family, affects triatomine transmitters of Chagas disease, which is endemic in Latin America but also expanding its worldwide distribution. To this end, we attempted virus replication in Diptera, Aedes albopictus (clone C6/36) and Lepidoptera Spodoptera frugiperda (SF9, SF21) and High Five (H5) cell lines. The methodologies used were transfection process, direct inoculation (purified virus), and inoculation of purified virus with trypsin. Results were confirmed by SDS-PAGE, Western blotting, RT-PCR, electron microscopy, and immunofluorescence. According to the results obtained, further analysis of susceptibility/infection of H5 cells to TrV required to be studied. PMID:25481388

  11. Protective and Pathogenic Responses to Chikungunya Virus Infection

    PubMed Central

    Long, Kristin M.; Heise, Mark T.

    2015-01-01

    Chikungunya virus (CHIKV) is an arbovirus responsible for causing epidemic outbreaks of human disease characterized by painful and often debilitating arthralgia. Recently CHIKV has moved into the Caribbean and the Americas resulting in massive outbreaks in naïve human populations. Given the importance of CHIKV as an emerging disease, a significant amount of effort has gone into interpreting the virus-host interactions that contribute to protection or virus-induced pathology following CHIKV infection, with the long term goal of using this information to develop new therapies or safe and effective anti-CHIKV vaccines. This work has made it clear that numerous distinct host responses are involved in the response to CHIKV infection, where some aspects of the host innate and adaptive immune response protect from or limit virus-induced disease, while other pathways actually exacerbate the virus-induced disease process. This review will discuss mechanisms that have been identified as playing a role in the host response to CHIKV infection and illustrate the importance of carefully evaluating these responses to determine whether they play a protective or pathologic role during CHIKV infection. PMID:26366337

  12. Persistent infection of chimpanzees with human immunodeficiency virus: serological responses and properties of reisolated viruses.

    PubMed Central

    Nara, P L; Robey, W G; Arthur, L O; Asher, D M; Wolff, A V; Gibbs, C J; Gajdusek, D C; Fischinger, P J

    1987-01-01

    Persistent infection by human immunodeficiency virus (HIV-1) in the chimpanzee may be valuable for immunopathologic and potential vaccine evaluation. Two HIV strains, the tissue culture-derived human T-cell lymphotropic virus type IIIB (HTLV-IIIB) and in vivo serially passaged lymphadenopathy-associated virus type 1 (LAV-1), were injected intravenously into chimpanzees. Two animals received HTLV-IIIB as either virus-infected H9 cells or cell-free virus. A third animal received chimpanzee-passaged LAV-1. Evaluation of their sera for virus-specific serologic changes, including neutralizations, was done during a 2-year period. During this period all animals had persistently high titers of antibodies to viral core and envelope antigens. All three animals developed a progressively increasing type-specific neutralizing LAV-1 versus HTLV-IIIB antibody titer during the 2-year observation period which broadened in specificity to include HTLV-HIRF, HTLV-IIIMN, and HTLV-IIICC after 6 to 12 months. The antibody titers against both viruses were still increasing by 2 years after experimental virus inoculation. Sera from all animals were capable of neutralizing both homologously and heterologously reisolated virus from chimpanzees. A slightly more rapid type-specific neutralizing response was noted for the animal receiving HTLV-IIIB-infected cells compared with that for cell-free HTLV-IIIB. Sera from all persistently infected chimpanzees were capable of mediating group-specific antibody-mediated complement-dependent cytolysis of HIV-infected cells derived from all isolates tested. Viruses reisolated from all three animals at 20 months after inoculation revealed very similar peptide maps of their respective envelope gp120s, as determined by two-dimensional chymotrypsin oligopeptide analysis. One peptide, however, from the original HTLV-IIIB-inoculated virus was deleted in viruses from all three animals, and in addition, we noted the appearance of a new or modified peptide which

  13. Persistent infection of chimpanzees with human immunodeficiency virus: serological responses and properties of reisolated viruses.

    PubMed

    Nara, P L; Robey, W G; Arthur, L O; Asher, D M; Wolff, A V; Gibbs, C J; Gajdusek, D C; Fischinger, P J

    1987-10-01

    Persistent infection by human immunodeficiency virus (HIV-1) in the chimpanzee may be valuable for immunopathologic and potential vaccine evaluation. Two HIV strains, the tissue culture-derived human T-cell lymphotropic virus type IIIB (HTLV-IIIB) and in vivo serially passaged lymphadenopathy-associated virus type 1 (LAV-1), were injected intravenously into chimpanzees. Two animals received HTLV-IIIB as either virus-infected H9 cells or cell-free virus. A third animal received chimpanzee-passaged LAV-1. Evaluation of their sera for virus-specific serologic changes, including neutralizations, was done during a 2-year period. During this period all animals had persistently high titers of antibodies to viral core and envelope antigens. All three animals developed a progressively increasing type-specific neutralizing LAV-1 versus HTLV-IIIB antibody titer during the 2-year observation period which broadened in specificity to include HTLV-HIRF, HTLV-IIIMN, and HTLV-IIICC after 6 to 12 months. The antibody titers against both viruses were still increasing by 2 years after experimental virus inoculation. Sera from all animals were capable of neutralizing both homologously and heterologously reisolated virus from chimpanzees. A slightly more rapid type-specific neutralizing response was noted for the animal receiving HTLV-IIIB-infected cells compared with that for cell-free HTLV-IIIB. Sera from all persistently infected chimpanzees were capable of mediating group-specific antibody-mediated complement-dependent cytolysis of HIV-infected cells derived from all isolates tested. Viruses reisolated from all three animals at 20 months after inoculation revealed very similar peptide maps of their respective envelope gp120s, as determined by two-dimensional chymotrypsin oligopeptide analysis. One peptide, however, from the original HTLV-IIIB-inoculated virus was deleted in viruses from all three animals, and in addition, we noted the appearance of a new or modified peptide which

  14. The Human Immunodeficiency Virus: Infectivity and Mechanisms of Pathogenesis

    NASA Astrophysics Data System (ADS)

    Fauci, Anthony S.

    1988-02-01

    Infection with the human immunodeficiency virus (HIV) results in a profound immunosuppression due predominantly to a selective depletion of helper/inducer T lymphocytes that express the receptor for the virus (the CD4 molecule). HIV also has tropism for the brain leading to neuropsychiatric abnormalities. Besides inducing cell death, HIV can interfere with T4 cell function by various mechanisms. The monocyte serves as a reservoir for HIV and is relatively refractory to its cytopathic effects. HIV can exist in a latent or chronic form which can be converted to a productive infection by a variety of inductive signals.

  15. Beet western yellows virus infects the carnivorous plant Nepenthes mirabilis.

    PubMed

    Miguel, Sissi; Biteau, Flore; Mignard, Benoit; Marais, Armelle; Candresse, Thierry; Theil, Sébastien; Bourgaud, Frédéric; Hehn, Alain

    2016-08-01

    Although poleroviruses are known to infect a broad range of higher plants, carnivorous plants have not yet been reported as hosts. Here, we describe the first polerovirus naturally infecting the pitcher plant Nepenthes mirabilis. The virus was identified through bioinformatic analysis of NGS transcriptome data. The complete viral genome sequence was assembled from overlapping PCR fragments and shown to share 91.1 % nucleotide sequence identity with the US isolate of beet western yellows virus (BWYV). Further analysis of other N. mirabilis plants revealed the presence of additional BWYV isolates differing by several insertion/deletion mutations in ORF5. PMID:27180098

  16. Herpes Simplex Virus Products in Productive and Abortive Infection

    PubMed Central

    Spring, Susan B.; Roizman, Bernard; Schwartz, Jerome

    1968-01-01

    Herpes simplex virus strain MPdk− multiplies in HEp-2 cells, but not in dog kidney (DK) cells. Strain MPdk+sp, a multistep mutant of MPdk−, multiplies in both HEp-2 and DK cells. Stabilized lysates of productively infected cells yield three macromolecular aggregates of viral deoxyribonucleic acid and protein banding in CsCl gradients at densities of 1.285 g/cm3 (α), 1.325 g/cm3 (β), and 1.37 to 1.45 g/cm3 (γ). Similar lysates from abortively infected cells yield only the β and γ bands. Electron microscopic examination revealed that (i) the α band contained enveloped nucleocapsids, whereas the β band contained naked nucleocapsids and particles tentatively identified as internal components of the nucleocapsids, and that (ii) the enveloped virions and reduplication of cellular membranes observed in thin sections of productively infected cells were absent from abortively infected cells. Studies of the surface antigens of infected cells in a cytolytic system described previously revealed that abortively infected cells contained approximately 10-fold less virus-induced surface antigen than did productively infected cells. From these and other data published previously, we concluded that infectious MPdk− virions are not made in DK cells because (i) functional viral products necessary for the envelopment of the nucleocapsid are not made, and (ii) capsid proteins and some nonstructural products specified by the virus malfunction. Images PMID:4316018

  17. Co-infection of mallards with low virulence Newcastle disease virus and low pathogenic avian influenza virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Waterfowl are considered the natural reservoirs of low pathogenic avian influenza viruses (LPAIV) and low virulence Newcastle disease viruses (loNDV). The objective of this study was to investigate the effect of co-infections with loNDV and LPAIV on the infectivity and excretion of these viruses in ...

  18. Experimental evidence of hepatitis A virus infection in pigs.

    PubMed

    Song, Young-Jo; Park, Woo-Jung; Park, Byung-Joo; Kwak, Sang-Woo; Kim, Yong-Hyeon; Lee, Joong-Bok; Park, Seung-Yong; Song, Chang-Seon; Lee, Sang-Won; Seo, Kun-Ho; Kang, Young-Sun; Park, Choi-Kyu; Song, Jae-Young; Choi, In-Soo

    2016-04-01

    Hepatitis A virus (HAV) is the leading cause of acute viral hepatitis worldwide, with HAV infection being restricted to humans and nonhuman primates. In this study, HAV infection status was serologically determined in domestic pigs and experimental infections of HAV were attempted to verify HAV infectivity in pigs. Antibodies specific to HAV or HAV-like agents were detected in 3.5% of serum samples collected from pigs in swine farms. When the pigs were infected intravenously with 2 × 10(5) 50% tissue culture infectious dose (TCID50 ) of HAV, shedding of the virus in feces, viremia, and seroconversion were detected. In pigs orally infected with the same quantity of HAV, viral shedding was detected only in feces. HAV genomic RNA was detected in the liver and bile of intravenously infected pigs, but only in the bile of orally infected pigs. In further experiments, pigs were intravenously infected with 6 × 10(5) TCID50 of HAV. Shedding of HAV in feces, along with viremia and seroconversion, were confirmed in infected pigs but not in sentinel pigs. HAV genomic RNA was detected in the liver, bile, spleen, lymph node, and kidney of the infected pigs. HAV antigenomic RNA was detected in the spleen of one HAV-infected pig, suggesting HAV replication in splenic cells. Infiltration of inflammatory cells was observed in the livers of infected pigs but not in controls. This is the first experimental evidence to demonstrate that human HAV strains can infect pigs. PMID:26381440

  19. Adaptive immune response during hepatitis C virus infection

    PubMed Central

    Larrubia, Juan Ramón; Moreno-Cubero, Elia; Lokhande, Megha Uttam; García-Garzón, Silvia; Lázaro, Alicia; Miquel, Joaquín; Perna, Cristian; Sanz-de-Villalobos, Eduardo

    2014-01-01

    Hepatitis C virus (HCV) infection affects about 170 million people worldwide and it is a major cause of liver cirrhosis and hepatocellular carcinoma. HCV is a hepatotropic non-cytopathic virus able to persist in a great percentage of infected hosts due to its ability to escape from the immune control. Liver damage and disease progression during HCV infection are driven by both viral and host factors. Specifically, adaptive immune response carries out an essential task in controlling non-cytopathic viruses because of its ability to recognize infected cells and to destroy them by cytopathic mechanisms and to eliminate the virus by non-cytolytic machinery. HCV is able to impair this response by several means such as developing escape mutations in neutralizing antibodies and in T cell receptor viral epitope recognition sites and inducing HCV-specific cytotoxic T cell anergy and deletion. To impair HCV-specific T cell reactivity, HCV affects effector T cell regulation by modulating T helper and Treg response and by impairing the balance between positive and negative co-stimulatory molecules and between pro- and anti-apoptotic proteins. In this review, the role of adaptive immune response in controlling HCV infection and the HCV mechanisms to evade this response are reviewed. PMID:24707125

  20. Inhibition of apoptosis in human immunodeficiency virus-infected cells enhances virus production and facilitates persistent infection.

    PubMed Central

    Antoni, B A; Sabbatini, P; Rabson, A B; White, E

    1995-01-01

    Apoptosis is one of several mechanisms by which human immunodeficiency virus type 1 (HIV-1) exerts its cytopathic effects. CD4+ Jurkat T-cell lines overexpressing the adenovirus E1B 19K protein, a potent inhibitor of apoptosis, were used to examine the consequences of inhibition of apoptosis during acute and chronic HIV-1 infections. E1B 19K protein expression inhibited HIV-induced apoptosis, enhanced virus production, and established high levels of persistent viral infection. One E1B 19K-expressing line appeared to undergo HIV-induced death via a nonapoptotic mechanism, illustrating that HIV infection results in lymphocyte depletion through multiple pathways. Increased virus production associated with sustained cell viability suggests that therapeutic approaches involving inhibition of HIV-induced programmed cell death may be problematic. PMID:7884884

  1. Experimental Infection of Horses with West Nile virus

    PubMed Central

    Bowen, Richard A.; Cropp, Bruce C.; Sullivan, Kevin G.; Davis, Brent S.; Komar, Nieholas; Godsey, Marvin; Baker, Dale; Hettler, Danielle L.; Holmes, Derek A.; Biggerstaff, Brad J.; Mitchell, Carl J.

    2002-01-01

    A total of 12 horses of different breeds and ages were infected with West Nile virus (WNV) via the bites of infected Aedes albopictus mosquitoes. Half the horses were infected with a viral isolate from the brain of a horse (BC787), and half were infected with an isolate from crow brain (NY99-6625); both were NY99 isolates. Postinfection, uninfected female Ae. albopictus fed on eight of the infected horses. In the first trial, Nt antibody titers reached >1:320, 1:20, 1:160, and 1:80 for horses 1 to 4, respectively. In the second trial, the seven horses with subclinical infections developed Nt antibody titers >1:10 between days 7 and 11 post infection. The highest viremia level in horses fed upon by the recipient mosquitoes was approximately 460 Vero cell PFU/mL. All mosquitoes that fed upon viremic horses were negative for the virus. Horses infected with the NY99 strain of WNV develop low viremia levels of short duration; therefore, infected horses are unlikely to serve as important amplifying hosts for WNV in nature. PMID:11971771

  2. Microglial activation induces neuronal death in Chandipura virus infection

    PubMed Central

    Verma, Abhishek Kumar; Ghosh, Sourish; Pradhan, Sreeparna; Basu, Anirban

    2016-01-01

    Neurotropic viruses induce neurodegeneration either directly by activating host death domains or indirectly through host immune response pathways. Chandipura Virus (CHPV) belonging to family Rhabdoviridae is ranked among the emerging pathogens of the Indian subcontinent. Previously we have reported that CHPV induces neurodegeneration albeit the root cause of this degeneration is still an open question. In this study we explored the role of microglia following CHPV infection. Phenotypic analysis of microglia through lectin and Iba-1 staining indicated cells were in an activated state post CHPV infection in cortical region of the infected mouse brain. Cytokine Bead Array (CBA) analysis revealed comparatively higher cytokine and chemokine levels in the same region. Increased level of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), Nitric Oxide (NO) and Reactive Oxygen species (ROS) in CHPV infected mouse brain indicated a strong inflammatory response to CHPV infection. Hence it was hypothesized through our analyses that this inflammatory response may stimulate the neuronal death following CHPV infection. In order to validate our hypothesis supernatant from CHPV infected microglial culture was used to infect neuronal cell line and primary neurons. This study confirmed the bystander killing of neurons due to activation of microglia post CHPV infection. PMID:26931456

  3. New perspectives for preventing hepatitis C virus liver graft infection.

    PubMed

    Felmlee, Daniel J; Coilly, Audrey; Chung, Raymond T; Samuel, Didier; Baumert, Thomas F

    2016-06-01

    Hepatitis C virus (HCV) infection is a leading cause of end-stage liver disease that necessitates liver transplantation. The incidence of virus-induced cirrhosis and hepatocellular carcinoma continues to increase, making liver transplantation increasingly common. Infection of the engrafted liver is universal and accelerates progression to advanced liver disease, with 20-30% of patients having cirrhosis within 5 years of transplantation. Treatments of chronic HCV infection have improved dramatically, albeit with remaining challenges of failure and access, and therapeutic options to prevent graft infection during liver transplantation are emerging. Developments in directed use of new direct-acting antiviral agents (DAAs) to eliminate circulating HCV before or after transplantation in the past 5 years provide renewed hope for prevention and treatment of liver graft infection. Identification of the ideal regimen and use of DAAs reveals new ways to treat this specific population of patients. Complementing DAAs, viral entry inhibitors have been shown to prevent liver graft infection in animal models and delay graft infection in clinical trials, which shows their potential for use concomitant to transplantation. We review the challenges and pathology associated with HCV liver graft infection, highlight current and future strategies of DAA treatment timing, and discuss the potential role of entry inhibitors that might be used synergistically with DAAs to prevent or treat graft infection. PMID:27301929

  4. Natural History of Primary Epstein-Barr Virus Infection in Children of Mothers Infected with Human Immunodeficiency Virus Type 1

    PubMed Central

    Jenson, Hal; McIntosh, Kenneth; Pitt, Jane; Husak, Scott; Tan, Ming; Bryson, Yvonne; Easley, Kirk

    2015-01-01

    The natural history of Epstein-Barr virus (EBV) infection in 556 infants born to 517 human immunodeficiency virus (HIV) type 1–infected mothers was studied in a prospective, multicenter, cohort study. HIV-1–infected children had a cumulative EBV infection rate similar to HIV-1–uninfected children at age 3 years (77.8% vs. 84.9%) but had more frequent oropharyngeal EBV shedding (50.4% vs. 28.2%; P < .001). The probability of shedding decreased with longer time from EBV seroconversion and was similar to that of HIV-1–uninfected children 3 years after seroconversion. HIV-1–infected children identified as rapid progressors shed EBV more frequently than nonrapid progressors (69.4% vs.41.0%; P = .01). HIV-1–infected children with EBV infection had higher mean CD8 cell counts. EBV infection did not have an independent effect on mean CD4 cell counts, percent CD4, IgG levels, HIV-1 RNA levels, lymphadenopathy, hepatomegaly, or splenomegaly. Early EBV infection is common in children born to HIV-1–infected mothers. Children with rapidly progressive HIV-1 disease have more frequent EBV shedding. PMID:10228060

  5. Chromatin assembly on herpes simplex virus genomes during lytic infection

    PubMed Central

    Lu, Xu; Triezenberg, Steven J

    2009-01-01

    The human herpes simplex viruses HSV-1 and HSV-2 infect a significant portion of the human population. Both viruses can undergo lytic infection in epithelial cells and establish lifelong latency in neuronal cells. The large HSV-1 DNA genomes have long been considered to be devoid of histones both inside the virion particle and inside the cell during lytic infection, but to be packaged in repressive chromatin during latency. However, recent reports indicate that many histone and non-histone chromosomal proteins can associate with viral DNA during lytic infection and may influence important events during the HSV-1 lytic cycle. In this article, we summarize recent developments in this field and their implications. PMID:19682614

  6. [HIV infection and parenteral virus hepatitis in the Krasnodar territory].

    PubMed

    Larin, F I; Lebedev, V V; Red'ko, A N

    2005-01-01

    The analysis of the morbidity dynamics of HIV infection, hepatitis B and C in the Krasnodar territory for 1996-2003 is presented. The tendency of strengthening direct correlation between age-dependent rates in these groups of diseases has been established. The correlation coefficient (rxy) is at present +0.851 (HIV infection-virus hepatitis B) and +0.892 (HIV infection-virus hepatitis C). The highest levels of primary morbidity are registered in persons aged 20-39 years. The established epidemiological parallels between HIV infection and parenteral hepatitis require the development of the unified strategy of the prophylaxis of these diseases on the federal and regional levels. PMID:16028521

  7. Influenza A Virus Infection, Innate Immunity, and Childhood

    PubMed Central

    Coates, Bria M.; Staricha, Kelly L.; Wiese, Kristin M.; Ridge, Karen M.

    2016-01-01

    Infection with influenza A virus is responsible for considerable morbidity and mortality in children worldwide. While it is apparent that adequate activation of the innate immune system is essential for pathogen clearance and host survival, an excessive inflammatory response to infection is detrimental to the young host. A review of the literature indicates that innate immune responses change throughout childhood. Whether these changes are genetically programmed or triggered by environmental cues is unknown. The objectives of this review are to summarize the role of innate immunity in influenza A virus infection in the young child and to highlight possible differences between children and adults that may make children more susceptible to severe influenza A infection. A better understanding of age-related differences in innate immune signaling will be essential to improve care for this high-risk population. PMID:26237589

  8. Transcriptome analysis of feline infectious peritonitis virus infection.

    PubMed

    Mehrbod, Parvaneh; Harun, Mohammad Syamsul Reza; Shuid, Ahmad Naqib; Omar, Abdul Rahman

    2015-01-01

    Feline infectious peritonitis (FIP) is a lethal systemic disease caused by FIP virus (FIPV). There are no effective vaccines or treatment available, and the virus virulence determinants and pathogenesis are not fully understood. Here, we describe the sequencing of RNA extracted from Crandell Rees Feline Kidney (CRFK) cells infected with FIPV using the Illumina next-generation sequencing approach. Bioinformatics analysis, based on Felis catus 2X annotated shotgun reference genome, using CLC bio Genome Workbench is used to map both control and infected cells. Kal's Z test statistical analysis is used to analyze the differentially expressed genes from the infected CRFK cells. In addition, RT-qPCR analysis is used for further transcriptional profiling of selected genes in infected CRFK cells and Peripheral Blood Mononuclear Cells (PBMCs) from healthy and FIP-diagnosed cats. PMID:25720485

  9. Fatal Cowpox Virus Infection in an Aborted Foal.

    PubMed

    Franke, Annika; Kershaw, Olivia; Jenckel, Maria; König, Lydia; Beer, Martin; Hoffmann, Bernd; Hoffmann, Donata

    2016-06-01

    The article describes the isolation of a cowpox virus (CPXV) isolate originating from a horse. The skin of a foal, aborted in the third trimester, displayed numerous cutaneous papules. The histological examination showed A-type inclusion bodies within the lesion, typical for CPXV infections. This suspicion was confirmed by real-time PCR where various organs were analyzed. From skin samples, virus isolation was successfully performed. Afterwards, the whole genome of this new isolate "CPXV Amadeus" was sequenced by next-generation technology. Phylogenetic analysis clearly showed that "CPXV Amadeus" belongs to the "CPXV-like 1" clade. To our opinion, the study provides important additional information on rare accidental CPXV infections. From the natural hosts, the voles, species such as rats, cats, or different zoo animals are occasionally infected, but until now only two horse cases are described. In addition, there are new insights toward congenital CPXV infections. PMID:27159333

  10. PRRSV receptors and their roles in virus infection.

    PubMed

    Shi, Chongxu; Liu, Yali; Ding, Yaozhong; Zhang, Yongguang; Zhang, Jie

    2015-05-01

    Porcine reproductive and respiratory syndrome virus (PRRSV) has a restricted cell tropism and prefers to invade well-differentiated cells of the monocyte/macrophage lineage, such as pulmonary alveolar macrophages and African green monkey kidney cell line MA-104 and its derivatives, such as Marc-145, Vero and CL-2621. PRRSV infection of the host cells actually is a receptor-mediated endocytosis and replication process. The presence and absence of the cellular receptors decide whether the cell lines are permissive or non-permissive to PRRSV infection. Several PRRSV non-permissive cell lines, such as BHK-21, PK-15 and CHO-K1, have been shown to become sensitive to the virus infection upon expression of the recombinant receptor proteins. Up to now, heparin sulfate, sialoadhesin, CD163, CD151 and vimentin have been identified as the important PRRSV receptors via their involvement in virus attachment, internalization or uncoating. Each receptor is characterized by the distribution in different cells, the function in virus different infection stages and the interaction model with the viral proteins or genes. Joint forces of the receptors recently attract attentions due to the specific function. PRRSV receptors have become the targets for designing the new anti-viral reagents or the recombinant cell lines used for isolating the viruses or developing more effective vaccines due to their more conserved sequences compared with the genetic variation of the virus. In this paper, the role of PRRSV receptors and the molecular mechanism of the interaction between the virus and the receptors are reviewed. PMID:25666932

  11. Macrophages in Progressive Human Immunodeficiency Virus/Simian Immunodeficiency Virus Infections.

    PubMed

    DiNapoli, Sarah R; Hirsch, Vanessa M; Brenchley, Jason M

    2016-09-01

    The cells that are targeted by primate lentiviruses (HIV and simian immunodeficiency virus [SIV]) are of intense interest given the renewed effort to identify potential cures for HIV. These viruses have been reported to infect multiple cell lineages of hematopoietic origin, including all phenotypic and functional CD4 T cell subsets. The two most commonly reported cell types that become infected in vivo are memory CD4 T cells and tissue-resident macrophages. Though viral infection of CD4 T cells is routinely detected in both HIV-infected humans and SIV-infected Asian macaques, significant viral infection of macrophages is only routinely observed in animal models wherein CD4 T cells are almost entirely depleted. Here we review the roles of macrophages in lentiviral disease progression, the evidence that macrophages support viral replication in vivo, the animal models where macrophage-mediated replication of SIV is thought to occur, how the virus can interact with macrophages in vivo, pathologies thought to be attributed to viral replication within macrophages, how viral replication in macrophages might contribute to the asymptomatic phase of HIV/SIV infection, and whether macrophages represent a long-lived reservoir for the virus. PMID:27307568

  12. Neuromuscular complications of human immunodeficiency virus infection and antiretroviral therapy.

    PubMed Central

    Miller, R G

    1994-01-01

    At least 4 distinct peripheral neuropathy syndromes occur in patients infected with the human immunodeficiency virus. The most common, painful sensory neuropathy, may be related to the viral infection or may be medication induced and is treated symptomatically. The other 3, chronic inflammatory demyelinating polyradiculoneuropathy, mononeuropathy multiplex (some patients), and the progressive polyradiculopathies related to the acquired immunodeficiency syndrome, may all respond to appropriate therapy. Both inflammatory myopathy and zidovudine myopathy also abate with early diagnosis and treatment. PMID:8048229

  13. Previous infection with a mesogenic strain of newcastle disease virus prevents infection with a highly pathogenic avian influenza virus in chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Avian influenza virus (AIV) and Newcastle disease virus (NDV) are two of the most important viruses affecting poultry worldwide. Co-infections of poultry with AIV and NDV are a problem from both the clinical point of view and the diagnosis of these viruses, but little is known on the interactions b...

  14. Experimental infection of vertebrates of the Pocomoke Cypress Swamp, Maryland with Keystone and Jamestown Canyon viruses.

    PubMed

    Watts, D M; Tammariello, R F; Dalrymple, J M; Eldridge, B F; Russell, P K; Top, F H

    1979-03-01

    Experimental studies were conducted to assess the susceptibility of white-tailed deer (Odocoileus virginianus), gray squirrels (Sciurus carolinensis), and cottontail rabbits (Sylvilagus floridanus) to Jamestown Canyon (JC) and/or Keystone (KEY) virus infection. Viremia occurred in 5 of 6 deer inoculated with JC virus; however, all deer developed KEY virus neutralizing antibody. Based on the observation that antibody elicited by primary infection of deer with either KEY or JC virus exhibited partial heterologous neutralization in vitro, cross-challenge experiments were performed in these animals. Keystone virus failed to infect deer 30 days post primary JC virus infection; however, deer became infected when challenged with KEY virus 80 days after the initial JC virus infection as indicated by a substantial increase in antibody titer. Similarly, JC virus failed to produce viremia in immune animals infected with KEY virus 80 days previously, although 2 of the 3 animals challenged had serological evidence of infection. Three field-collected cottontail rabbits with no evidence of KEY antibody were readily susceptible to KEY virus infection and developed viremias of 1-4 days' duration; rabbits with KEY virus antibody did not develop viremia upon KEY virus challenge. Eight antibody-negative field-collected gray squirrels became viremic following injection with KEY virus; however, a comparable group of squirrels did not become viremic when injected with JC virus. PMID:453437

  15. The role of IKKβ in Venezuelan equine encephalitis virus infection.

    PubMed

    Amaya, Moushimi; Voss, Kelsey; Sampey, Gavin; Senina, Svetlana; de la Fuente, Cynthia; Mueller, Claudius; Calvert, Valerie; Kehn-Hall, Kylene; Carpenter, Calvin; Kashanchi, Fatah; Bailey, Charles; Mogelsvang, Soren; Petricoin, Emanuel; Narayanan, Aarthi

    2014-01-01

    Venezuelan equine encephalitis virus (VEEV) belongs to the genus Alphavirus, family Togaviridae. VEEV infection is characterized by extensive inflammation and studies from other laboratories implicated an involvement of the NF-κB cascade in the in vivo pathology. Initial studies indicated that at early time points of VEEV infection, the NF-κB complex was activated in cells infected with the TC-83 strain of VEEV. One upstream kinase that contributes to the phosphorylation of p65 is the IKKβ component of the IKK complex. Our previous studies with Rift valley fever virus, which exhibited early activation of the NF-κB cascade in infected cells, had indicated that the IKKβ component underwent macromolecular reorganization to form a novel low molecular weight form unique to infected cells. This prompted us to investigate if the IKK complex undergoes a comparable macromolecular reorganization in VEEV infection. Size-fractionated VEEV infected cell extracts indicated a macromolecular reorganization of IKKβ in VEEV infected cells that resulted in formation of lower molecular weight complexes. Well-documented inhibitors of IKKβ function, BAY-11-7082, BAY-11-7085 and IKK2 compound IV, were employed to determine whether IKKβ function was required for the production of infectious progeny virus. A decrease in infectious viral particles and viral RNA copies was observed with inhibitor treatment in the attenuated and virulent strains of VEEV infection. In order to further validate the requirement of IKKβ for VEEV replication, we over-expressed IKKβ in cells and observed an increase in viral titers. In contrast, studies carried out using IKKβ(-/-) cells demonstrated a decrease in VEEV replication. In vivo studies demonstrated that inhibitor treatment of TC-83 infected mice increased their survival. Finally, proteomics studies have revealed that IKKβ may interact with the viral protein nsP3. In conclusion, our studies have revealed that the host IKKβ protein may be

  16. The Role of IKKβ in Venezuelan Equine Encephalitis Virus Infection

    PubMed Central

    Amaya, Moushimi; Voss, Kelsey; Sampey, Gavin; Senina, Svetlana; de la Fuente, Cynthia; Mueller, Claudius; Calvert, Valerie; Kehn-Hall, Kylene; Carpenter, Calvin; Kashanchi, Fatah; Bailey, Charles; Mogelsvang, Soren; Petricoin, Emanuel; Narayanan, Aarthi

    2014-01-01

    Venezuelan equine encephalitis virus (VEEV) belongs to the genus Alphavirus, family Togaviridae. VEEV infection is characterized by extensive inflammation and studies from other laboratories implicated an involvement of the NF-κB cascade in the in vivo pathology. Initial studies indicated that at early time points of VEEV infection, the NF-κB complex was activated in cells infected with the TC-83 strain of VEEV. One upstream kinase that contributes to the phosphorylation of p65 is the IKKβ component of the IKK complex. Our previous studies with Rift valley fever virus, which exhibited early activation of the NF-κB cascade in infected cells, had indicated that the IKKβ component underwent macromolecular reorganization to form a novel low molecular weight form unique to infected cells. This prompted us to investigate if the IKK complex undergoes a comparable macromolecular reorganization in VEEV infection. Size-fractionated VEEV infected cell extracts indicated a macromolecular reorganization of IKKβ in VEEV infected cells that resulted in formation of lower molecular weight complexes. Well-documented inhibitors of IKKβ function, BAY-11-7082, BAY-11-7085 and IKK2 compound IV, were employed to determine whether IKKβ function was required for the production of infectious progeny virus. A decrease in infectious viral particles and viral RNA copies was observed with inhibitor treatment in the attenuated and virulent strains of VEEV infection. In order to further validate the requirement of IKKβ for VEEV replication, we over-expressed IKKβ in cells and observed an increase in viral titers. In contrast, studies carried out using IKKβ−/− cells demonstrated a decrease in VEEV replication. In vivo studies demonstrated that inhibitor treatment of TC-83 infected mice increased their survival. Finally, proteomics studies have revealed that IKKβ may interact with the viral protein nsP3. In conclusion, our studies have revealed that the host IKKβ protein may be

  17. Hepatitis E virus infection--a new threat for Europe.

    PubMed

    Łapiński, Tadeusz Wojciech; Jaroszewicz, Jerzy

    2016-01-01

    Of 20 million of patients infected with hepatitis E virus (HEV) worldwide 57 thousand dies each year. HEV-infection is not longer regarded as a diseases in developing endemic countries of Asia, Africa and Latin America. The majority of European countries faces increasing number of endemic infections. They are caused by seven different genotypes and be responsible for acute and chronic infections. HEV is of zoonotic origin causing infections in pigs and boars which are a source of infection for humans. Infections occur orally after consumption of infected water or meat. HEV-infection is most dangerous for patients receiving immunosuppressive therapy, infected with HIV, after transplantations of solid organs and elderly. In some patients, including pregnant women, acute HEV has a serious course with fatalities reaching even 25%. Chronic HEV-infection may develop in patients following solid organ transplantations and requires long-term antiviral therapy. HEV-infection is a growing public health problem in Europe, which implies the necessity of routine screening in selected populations, especially immunocompromised. PMID:27344467

  18. Alteration of cell cycle progression by Sindbis virus infection

    SciTech Connect

    Yi, Ruirong; Saito, Kengo; Isegawa, Naohisa; Shirasawa, Hiroshi

    2015-07-10

    We examined the impact of Sindbis virus (SINV) infection on cell cycle progression in a cancer cell line, HeLa, and a non-cancerous cell line, Vero. Cell cycle analyses showed that SINV infection is able to alter the cell cycle progression in both HeLa and Vero cells, but differently, especially during the early stage of infection. SINV infection affected the expression of several cell cycle regulators (CDK4, CDK6, cyclin E, p21, cyclin A and cyclin B) in HeLa cells and caused HeLa cells to accumulate in S phase during the early stage of infection. Monitoring SINV replication in HeLa and Vero cells expressing cell cycle indicators revealed that SINV which infected HeLa cells during G{sub 1} phase preferred to proliferate during S/G{sub 2} phase, and the average time interval for viral replication was significantly shorter in both HeLa and Vero cells infected during G{sub 1} phase than in cells infected during S/G{sub 2} phase. - Highlights: • SINV infection was able to alter the cell cycle progression of infected cancer cells. • SINV infection can affect the expression of cell cycle regulators. • SINV infection exhibited a preference for the timing of viral replication among the cell cycle phases.

  19. The Effects of High Temperature on Infection by Potato virus Y, Potato virus A, and Potato leafroll virus.

    PubMed

    Chung, Bong Nam; Canto, Tomas; Tenllado, Francisco; Choi, Kyung San; Joa, Jae Ho; Ahn, Jeong Joon; Kim, Chun Hwan; Do, Ki Seck

    2016-08-01

    We examined the effects of temperature on acquisition of Potato virus Y-O (PVY-O), Potato virus A (PVA), and Potato leafroll virus (PLRV) by Myzus persicae by performing transmission tests with aphids that acquired each virus at different temperatures. Infection by PVY-O/PVA and PLRV increased with increasing plant temperature in Nicotiana benthamiana and Physalis floridana, respectively, after being transmitted by aphids that acquired them within a temperature range of 10-20°C. However, infection rates subsequently decreased. Direct qRT-PCR of RNA extracted from a single aphid showed that PLRV infection increased in the 10-20°C range, but this trend also declined shortly thereafter. We examined the effect of temperature on establishment of virus infection. The greatest number of plants became infected when N. benthamiana was held at 20°C after inoculation with PVY-O or PVA. The largest number of P. floridana plants became infected with PLRV when the plants were maintained at 25°C. PLRV levels were highest in P. floridana kept at 20-25°C. These results indicate that the optimum temperatures for proliferation of PVY-O/PVA and PLRV differed. Western blot analysis showed that accumulations of PVY-O and PVA coat proteins (CPs) were lower at 10°C or 15°C than at 20°C during early infection. However, accumulation increased over time. At 25°C or 30°C, the CPs of both viruses accumulated during early infection but disappeared as time passed. Our results suggest that symptom attenuation and reduction of PVY-O and PVA CP accumulation at higher temperatures appear to be attributable to increased RNA silencing. PMID:27493607

  20. The Effects of High Temperature on Infection by Potato virus Y, Potato virus A, and Potato leafroll virus

    PubMed Central

    Chung, Bong Nam; Canto, Tomas; Tenllado, Francisco; Choi, Kyung San; Joa, Jae Ho; Ahn, Jeong Joon; Kim, Chun Hwan; Do, Ki Seck

    2016-01-01

    We examined the effects of temperature on acquisition of Potato virus Y-O (PVY-O), Potato virus A (PVA), and Potato leafroll virus (PLRV) by Myzus persicae by performing transmission tests with aphids that acquired each virus at different temperatures. Infection by PVY-O/PVA and PLRV increased with increasing plant temperature in Nicotiana benthamiana and Physalis floridana, respectively, after being transmitted by aphids that acquired them within a temperature range of 10–20°C. However, infection rates subsequently decreased. Direct qRT-PCR of RNA extracted from a single aphid showed that PLRV infection increased in the 10–20°C range, but this trend also declined shortly thereafter. We examined the effect of temperature on establishment of virus infection. The greatest number of plants became infected when N. benthamiana was held at 20°C after inoculation with PVY-O or PVA. The largest number of P. floridana plants became infected with PLRV when the plants were maintained at 25°C. PLRV levels were highest in P. floridana kept at 20–25°C. These results indicate that the optimum temperatures for proliferation of PVY-O/PVA and PLRV differed. Western blot analysis showed that accumulations of PVY-O and PVA coat proteins (CPs) were lower at 10°C or 15°C than at 20°C during early infection. However, accumulation increased over time. At 25°C or 30°C, the CPs of both viruses accumulated during early infection but disappeared as time passed. Our results suggest that symptom attenuation and reduction of PVY-O and PVA CP accumulation at higher temperatures appear to be attributable to increased RNA silencing. PMID:27493607

  1. Host sphingomyelin increases West Nile virus infection in vivo.

    PubMed

    Martín-Acebes, Miguel A; Gabandé-Rodríguez, Enrique; García-Cabrero, Ana M; Sánchez, Marina P; Ledesma, María Dolores; Sobrino, Francisco; Saiz, Juan-Carlos

    2016-03-01

    Flaviviruses, such as the dengue virus and the West Nile virus (WNV), are arthropod-borne viruses that represent a global health problem. The flavivirus lifecycle is intimately connected to cellular lipids. Among the lipids co-opted by flaviviruses, we have focused on SM, an important component of cellular membranes particularly enriched in the nervous system. After infection with the neurotropic WNV, mice deficient in acid sphingomyelinase (ASM), which accumulate high levels of SM in their tissues, displayed exacerbated infection. In addition, WNV multiplication was enhanced in cells from human patients with Niemann-Pick type A, a disease caused by a deficiency of ASM activity resulting in SM accumulation. Furthermore, the addition of SM to cultured cells also increased WNV infection, whereas treatment with pharmacological inhibitors of SM synthesis reduced WNV infection. Confocal microscopy analyses confirmed the association of SM with viral replication sites within infected cells. Our results unveil that SM metabolism regulates flavivirus infection in vivo and propose SM as a suitable target for antiviral design against WNV. PMID:26764042

  2. Epstein-Barr Virus Induced Epigenetic Alterations Following Transient Infection

    PubMed Central

    Queen, Krista J.; Shi, Mingxia; Zhang, Fangfang; Cvek, Urska; Scott, Rona S.

    2012-01-01

    Epstein-Barr virus (EBV) is a known tumor virus associated with an increasing array of malignancies; however, the association of the virus with certain malignancies is often erratic. To determine EBV’s contributions to tumorigenesis in a setting of incomplete association, a transient model of infection was established where a clonal CCL185 carcinoma cell line infected with recombinant EBV was allowed to lose viral genomes by withdrawal of selection pressure. Global gene expression comparing EBV-negative, transiently infected clones to uninfected controls identified expression changes in over 1000 genes. Among downregulated genes, several genes known to be DNA methylated in cancer were identified including E-cadherin and PYCARD. A cadherin switch, increased motility and enhanced cellular invasiveness present in EBV-positive cells were retained following viral loss indicating an epigenetic effect. Repression of PYCARD expression was due to increased promoter CpG methylation, whereas loss of E-cadherin expression after transient EBV infection did not correlate with increased DNA methylation of the E-cadherin promoter. Rather, repression of E-cadherin was consistent with formation of a repressive chromatin state. Decreased histone 3 or 4 acetylation at the promoter and 5’ end of the E-cadherin gene was observed in an EBV-negative, transiently infected clone relative to the uninfected controls. These results suggest that EBV can stably alter gene expression in a heritable fashion in formerly infected cells, while its own contribution to the oncogenic process is masked. PMID:23047626

  3. Induction of apoptosis in frog virus 3-infected cells.

    PubMed

    Chinchar, V G; Bryan, Locke; Wang, J; Long, Scott; Chinchar, G D

    2003-02-15

    The ability of frog virus 3 (FV3), the type species of the family Iridoviridae, to induce apoptosis was examined by monitoring DNA cleavage, chromatin condensation, and cell-surface expression of phosphotidylserine (PS) in fathead minnow (FHM) and baby hamster kidney (BHK) cells. In productively infected FHM cells, DNA fragmentation was first noted at 6-7 h postinfection and was clearly seen by 17 h postinfection, while chromatin condensation was detected at 8.5 h postinfection. As with some other viruses, FV3-induced apoptosis did not require de novo viral gene expression as both heat-inactivated and UV-inactivated virus readily triggered DNA fragmentation in FHM cells. Moreover, FV3-induced apoptosis was blocked in FHM cells by the pan-caspase inhibitor Z-VAD-FMK, suggesting that virus infection triggers programmed cell death through activation of the caspase cascade. FV3 infection also triggered apoptosis in BHK cells as monitored by TUNEL and annexin V binding assays. To determine whether FV3, similar to other large DNA viruses, encoded proteins that block or delay apoptosis, mock- and FV3-infected FHM cells were osmotically shocked and assayed for DNA fragmentation 3 hours later. DNA fragmentation was clearly seen whether or not shocked cells were previously infected with FV3, indicating that infection with FV3 did not block apoptosis induced by osmotic shock in FHM cells. The above results demonstrate that iridoviruses triggered apoptosis and that the induction of programmed cell death did not require viral gene expression. However, it remains to be determined if virion attachment to target cells is sufficient to induce cell death, or if apoptosis is triggered directly or indirectly by one or more virion-associated proteins. PMID:12642103

  4. The hepatitis delta virus and its infection

    SciTech Connect

    Rizzeto, M.; Gerin, J.L.; Purcell, R.H.

    1987-01-01

    This book contains over 50 papers. Some of the titles are: Structure and Replication of the Genome of Hepatitis Delta Virus; Clinical Significance of HDV RNA in HDV Disease; HBV DNA in Delta Chronic Carriers; Prevalance of HBV-DNA Among Anti-Hd Positive Patients; and Characterization of LKM/sub 1/ and LKM/sub 2/ Antigens.

  5. Dobrava-Belgrade Virus Spillover Infections, Germany

    PubMed Central

    Schlegel, Mathias; Klempa, Boris; Auste, Brita; Bemmann, Margrit; Schmidt-Chanasit, Jonas; Büchner, Thomas; Groschup, Martin H.; Meier, Markus; Balkema-Buschmann, Anne; Zoller, Hinrich; Krüger, Detlev H.

    2009-01-01

    We present the molecular identification of Apodemus agrarius (striped field mouse) as reservoir host of the Dobrava-Belgrade virus (DOBV) lineage DOBV-Aa in 3 federal states of Germany. Phylogenetic analyses provided evidence for multiple spillover of DOBV-Aa to A. flavicollis, a crucial prerequisite for host switch and genetic reassortment. PMID:19961690

  6. Potent neutralizing monoclonal antibodies against Ebola virus infection.

    PubMed

    Zhang, Qi; Gui, Miao; Niu, Xuefeng; He, Shihua; Wang, Ruoke; Feng, Yupeng; Kroeker, Andrea; Zuo, Yanan; Wang, Hua; Wang, Ying; Li, Jiade; Li, Chufang; Shi, Yi; Shi, Xuanling; Gao, George F; Xiang, Ye; Qiu, Xiangguo; Chen, Ling; Zhang, Linqi

    2016-01-01

    Ebola virus infections cause a deadly hemorrhagic disease for which no vaccines or therapeutics has received regulatory approval. Here we show isolation of three (Q206, Q314 and Q411) neutralizing monoclonal antibodies (mAbs) against the surface glycoprotein (GP) of Ebola virus identified in West Africa in 2014 through sequential immunization of Chinese rhesus macaques and antigen-specific single B cell sorting. These mAbs demonstrated potent neutralizing activities against both pseudo and live Ebola virus independent of complement. Biochemical, single particle EM, and mutagenesis analysis suggested Q206 and Q411 recognized novel epitopes in the head while Q314 targeted the glycan cap in the GP1 subunit. Q206 and Q411 appeared to influence GP binding to its receptor NPC1. Treatment with these mAbs provided partial but significant protection against disease in a mouse model of Ebola virus infection. These novel mAbs could serve as promising candidates for prophylactic and therapeutic interventions against Ebola virus infection. PMID:27181584

  7. Cyclophilin A protects mice against infection by influenza A virus

    PubMed Central

    Li, Jing; Chen, Can; Wong, Gary; Dong, Wei; Zheng, Weinan; Li, Yun; Sun, Lei; Zhang, Lianfeng; Gao, George F.; Bi, Yuhai; Liu, Wenjun

    2016-01-01

    Our previous studies indicate that Cyclophilin A (CypA) impairs the replication of influenza A virus in vitro. To further evaluate the antiviral functions of CypA and explore its mechanism, transgenic mice with overexpression of CypA by two specific promoters with SPC (CypA-SPC) or CMV (CypA-CMV) were developed. After challenge with the A/WSN/33(H1N1) influenza virus, CypA-SPC and CypA-CMV transgenic mice displayed nearly 2.5- and 3.8-fold stronger disease resistance to virus infection, respectively, compared to wild-type animals. Virus replication, pathological lesions and inflammatory cytokines were substantially reduced in both lines of transgenic mice. In addition, after infection there was an upregulation of genes associated with cell migration, immune function, and organ development; and a downregulation of genes associated with the positive regulation of immune cells and apoptosis in the peritoneal macrophages of CypA-overexpressing transgenic mice (CypA+). These results indicate that CypA is a key modulator of influenza virus resistance in mice, and that CypA+ mice constitutes an important model to study the roles of CypA in the regulation of immune responses and infections. PMID:27354005

  8. Cyclophilin A protects mice against infection by influenza A virus.

    PubMed

    Li, Jing; Chen, Can; Wong, Gary; Dong, Wei; Zheng, Weinan; Li, Yun; Sun, Lei; Zhang, Lianfeng; Gao, George F; Bi, Yuhai; Liu, Wenjun

    2016-01-01

    Our previous studies indicate that Cyclophilin A (CypA) impairs the replication of influenza A virus in vitro. To further evaluate the antiviral functions of CypA and explore its mechanism, transgenic mice with overexpression of CypA by two specific promoters with SPC (CypA-SPC) or CMV (CypA-CMV) were developed. After challenge with the A/WSN/33(H1N1) influenza virus, CypA-SPC and CypA-CMV transgenic mice displayed nearly 2.5- and 3.8-fold stronger disease resistance to virus infection, respectively, compared to wild-type animals. Virus replication, pathological lesions and inflammatory cytokines were substantially reduced in both lines of transgenic mice. In addition, after infection there was an upregulation of genes associated with cell migration, immune function, and organ development; and a downregulation of genes associated with the positive regulation of immune cells and apoptosis in the peritoneal macrophages of CypA-overexpressing transgenic mice (CypA+). These results indicate that CypA is a key modulator of influenza virus resistance in mice, and that CypA+ mice constitutes an important model to study the roles of CypA in the regulation of immune responses and infections. PMID:27354005

  9. Potent neutralizing monoclonal antibodies against Ebola virus infection

    PubMed Central

    Zhang, Qi; Gui, Miao; Niu, Xuefeng; He, Shihua; Wang, Ruoke; Feng, Yupeng; Kroeker, Andrea; Zuo, Yanan; Wang, Hua; Wang, Ying; Li, Jiade; Li, Chufang; Shi, Yi; Shi, Xuanling; Gao, George F.; Xiang, Ye; Qiu, Xiangguo; Chen, Ling; Zhang, Linqi

    2016-01-01

    Ebola virus infections cause a deadly hemorrhagic disease for which no vaccines or therapeutics has received regulatory approval. Here we show isolation of three (Q206, Q314 and Q411) neutralizing monoclonal antibodies (mAbs) against the surface glycoprotein (GP) of Ebola virus identified in West Africa in 2014 through sequential immunization of Chinese rhesus macaques and antigen-specific single B cell sorting. These mAbs demonstrated potent neutralizing activities against both pseudo and live Ebola virus independent of complement. Biochemical, single particle EM, and mutagenesis analysis suggested Q206 and Q411 recognized novel epitopes in the head while Q314 targeted the glycan cap in the GP1 subunit. Q206 and Q411 appeared to influence GP binding to its receptor NPC1. Treatment with these mAbs provided partial but significant protection against disease in a mouse model of Ebola virus infection. These novel mAbs could serve as promising candidates for prophylactic and therapeutic interventions against Ebola virus infection. PMID:27181584

  10. Global Reprogramming of Host SUMOylation during Influenza Virus Infection

    PubMed Central

    Domingues, Patricia; Golebiowski, Filip; Tatham, Michael H.; Lopes, Antonio M.; Taggart, Aislynn; Hay, Ronald T.; Hale, Benjamin G.

    2015-01-01

    Summary Dynamic nuclear SUMO modifications play essential roles in orchestrating cellular responses to proteotoxic stress, DNA damage, and DNA virus infection. Here, we describe a non-canonical host SUMOylation response to the nuclear-replicating RNA pathogen, influenza virus, and identify viral RNA polymerase activity as a major contributor to SUMO proteome remodeling. Using quantitative proteomics to compare stress-induced SUMOylation responses, we reveal that influenza virus infection triggers unique re-targeting of SUMO to 63 host proteins involved in transcription, mRNA processing, RNA quality control, and DNA damage repair. This is paralleled by widespread host deSUMOylation. Depletion screening identified ten virus-induced SUMO targets as potential antiviral factors, including C18orf25 and the SMC5/6 and PAF1 complexes. Mechanistic studies further uncovered a role for SUMOylation of the PAF1 complex component, parafibromin (CDC73), in potentiating antiviral gene expression. Our global characterization of influenza virus-triggered SUMO redistribution provides a proteomic resource to understand host nuclear SUMOylation responses to infection. PMID:26549460

  11. Broadly neutralizing antibodies abrogate established hepatitis C virus infection

    PubMed Central

    de Jong, Ype P.; Dorner, Marcus; Mommersteeg, Michiel C.; Xiao, Jing W.; Balazs, Alejandro B.; Robbins, Justin B.; Winer, Benjamin Y.; Gerges, Sherif; Vega, Kevin; Labitt, Rachael N.; Donovan, Bridget M.; Giang, Erick; Krishnan, Anuradha; Chiriboga, Luis; Charlton, Michael R.; Burton, Dennis R.; Baltimore, David; Law, Mansun; Rice, Charles M.; Ploss, Alexander

    2015-01-01

    Hepatitis C virus (HCV) establishes a chronic infection in the majority of exposed individuals and can cause cirrhosis and hepatocellular carcinoma. The role of antibodies directed against HCV in disease progression is poorly understood. Neutralizing antibodies (nAbs) can prevent HCV infection in vitro and in animal models. However, the effects of nAbs on an established HCV infection are unclear. Here, we demonstrate that three broadly nAbs, AR3A, AR3B and AR4A, delivered with adeno-associated viral (AAV) vectors can confer protection against viral challenge in humanized mice. Furthermore, we provide evidence that nAbs can abrogate an ongoing HCV infection in primary hepatocyte cultures and in a human liver chimeric mouse model. These results showcase a novel therapeutic approach to interfere with HCV infection exploiting a previously unappreciated need for HCV to continuously infect new hepatocytes in order to sustain chronicity. PMID:25232181

  12. Shedding of Hepatitis C Virus in Semen of Human Immunodeficiency Virus-Infected Men

    PubMed Central

    Turner, Samuel S.; Gianella, Sara; Yip, Marcus J-S.; van Seggelen, Wouter O.; Gillies, Robert D.; Foster, Andrew L.; Barbati, Zachary R.; Smith, Davey M.; Fierer, Daniel S.

    2016-01-01

    Background. The epidemic of sexually transmitted hepatitis C virus (HCV) infection among human immunodeficiency virus (HIV)-infected men who have sex with men (MSM) has been documented for over a decade. Despite this, there is no consensus as to the risk factors for sexual acquisition of HCV in these men. Methods. We obtained paired semen and blood samples at 2-week intervals from HIV-infected MSM with recent and chronic HCV infection and quantified HCV in semen. Results. Hepatitis C virus was quantified in 59 semen specimens from 33 men. Hepatitis C virus was shed in 16 (27%) of semen specimens from 11 (33%) of the men. Median HCV viral load (VL) in semen was 1.49 log10 IU/mL. Hepatitis C virus VL in blood was significantly higher at the time of HCV shedding in semen than when HCV shedding in semen was not detected (P = .002). Furthermore, there was a significant correlation between the HCV VL in blood and semen overall (rs = 0.41; P = .001), and in the subgroup with recent HCV infection (rs = 0.37; P = .02), but not in the subgroup with chronic HCV infection (rs = 0.34; P = .1). Conclusions. One third of HIV-infected MSM coinfected with HCV shed HCV into their semen. Based on the HCV VL in semen in this study, an average ejaculate would deliver up to 6630 IU of virus into the rectum of the receptive partner. Therefore, our data strongly support that condoms should be used during anal intercourse among MSM to prevent transmission of HCV. PMID:27186582

  13. Prevalence of Hepatitis B Virus Infection in Kenya, 2007.

    PubMed

    Ly, Kathleen N; Kim, Andrea A; Umuro, Mamo; Drobenuic, Jan; Williamson, John M; Montgomery, Joel M; Fields, Barry S; Teshale, Eyasu H

    2016-08-01

    Current estimates put the prevalence of hepatitis B virus (HBV) infection in Kenya at 5-8%. We determined the HBV infection prevalence in the human immunodeficiency virus (HIV)-negative Kenyan adult and adolescent population based on samples collected from a national survey. We analyzed data from HIV-negative participants in the 2007 Kenya AIDS Indicator Survey to estimate the HBV infection prevalence. We defined past or present HBV infection as presence of total hepatitis B core antibody (HBcAb), and chronic HBV infection (CHBI) as presence of both total HBcAb and hepatitis B surface antigen (HBsAg). We calculated crude and adjusted odds of HBV infection by demographic characteristics and risk factors using logistic regression analyses. Of 1,091 participants aged 15-64 years, approximately 31.5% (95% confidence interval [CI] = 28.0-35.3%) had exposure to HBV, corresponding to approximately 6.1 million (CI = 5.4-6.8 million) with past or present HBV infection. The estimated prevalence of CHBI was 2.1% (95% CI = 1.4-3.1%), corresponding to approximately 398,000 (CI = 261,000-602,000) with CHBI. CHBI is a major public health problem in Kenya, affecting approximately 400,000 persons. Knowing the HBV infection prevalence at baseline is important for planning and public health policy decision making and for monitoring the impact of viral hepatitis prevention programs. PMID:27273644

  14. Tissue culture system for infection with human hepatitis delta virus.

    PubMed Central

    Sureau, C; Jacob, J R; Eichberg, J W; Lanford, R E

    1991-01-01

    An in vitro culture system was developed for assaying the infectivity of the human hepatitis delta virus (HDV). Hepatocytes were isolated from chimpanzee liver and grown in a serum-free medium. Cells were shown to be infectible by HDV and to remain susceptible to infection for at least 3 weeks in culture, as evidenced by the appearance of RNA species characteristic of HDV replication as early as 6 days postinfection. When repeated experiments were carried out on cells derived from an animal free of hepatitis B virus (HBV), HDV infection occurred in a consistent fashion but there was no indication of infection with the HBV that was present in the inoculum. Despite numerous attempts with different sources of HBV inocula free of HDV, there was no evidence that indicated susceptibility of these cells to HBV infection. This observation may indicate that HBV and HDV use different modes of entry into hepatocytes. When cells derived from an HBV-infected animal were exposed to HDV, synthesis and release of progeny HDV particles were obtained in addition to HBV replication and production of Dane particles. Although not infectible with HBV, primary cultures of chimpanzee hepatocytes are capable of supporting part of the life cycle of HBV and the entire life cycle of HDV. Images PMID:2041075

  15. Persistent Infection with Ebola Virus under Conditions of Partial Immunity

    PubMed Central

    Gupta, Manisha; Mahanty, Siddhartha; Greer, Patricia; Towner, Jonathan S.; Shieh, Wun-Ju; Zaki, Sherif R.; Ahmed, Rafi; Rollin, Pierre E.

    2004-01-01

    Ebola hemorrhagic fever in humans is associated with high mortality; however, some infected hosts clear the virus and recover. The mechanisms by which this occurs and the correlates of protective immunity are not well defined. Using a mouse model, we determined the role of the immune system in clearance of and protection against Ebola virus. All CD8 T-cell-deficient mice succumbed to subcutaneous infection and had high viral antigen titers in tissues, whereas mice deficient in B cells or CD4 T cells cleared infection and survived, suggesting that CD8 T cells, independent of CD4 T cells and antibodies, are critical to protection against subcutaneous Ebola virus infection. B-cell-deficient mice that survived the primary subcutaneous infection (vaccinated mice) transiently depleted or not depleted of CD4 T cells also survived lethal intraperitoneal rechallenge for ≥25 days. However, all vaccinated B-cell-deficient mice depleted of CD8 T cells had high viral antigen titers in tissues following intraperitoneal rechallenge and died within 6 days, suggesting that memory CD8 T cells by themselves can protect mice from early death. Surprisingly, vaccinated B-cell-deficient mice, after initially clearing the infection, were found to have viral antigens in tissues later (day 120 to 150 post-intraperitoneal infection). Furthermore, following intraperitoneal rechallenge, vaccinated B-cell-deficient mice that were transiently depleted of CD4 T cells had high levels of viral antigen in tissues earlier (days 50 to 70) than vaccinated undepleted mice. This demonstrates that under certain immunodeficiency conditions, Ebola virus can persist and that loss of primed CD4 T cells accelerates the course of persistent infections. These data show that CD8 T cells play an important role in protection against acute disease, while both CD4 T cells and antibodies are required for long-term protection, and they provide evidence of persistent infection by Ebola virus suggesting that under

  16. Spatial Analysis of Feline Immunodeficiency Virus Infection in Cougars

    PubMed Central

    Wheeler, David C.; Waller, Lance A.; Biek, Roman

    2010-01-01

    The cougar (Puma concolor) is a large predatory feline found widely in the Americas that is susceptible to feline immunodeficiency virus (FIV), a fast-evolving lentivirus found in wild feline species that is analogous to simian immunodeficiency viruses in wild primates and belongs to the same family of viruses as human immunodeficiency virus. FIV infection in cougars can lead to a weakened immune system that creates opportunities for other infecting agents. FIV prevalence and lineages have been studied previously in several areas in the western United States, but typically without spatially explicit statistical techniques. To describe the distribution of FIV in a sample of cougars located in the northern Rocky Mountain region of North America, we first used kernel density ratio estimation to map the log relative risk of FIV. The risk surface showed a significant cluster of FIV in northwestern Montana. We also used Bayesian cluster models for genetic data to investigate the spatial structure of the feline immunodeficiency virus with virus genetic sequence data. A result of the models was two spatially distinct FIV lineages that aligned considerably with an interstate highway in Montana. Our results suggest that the use of spatial information and models adds novel insight when investigating an infectious animal disease. The results also suggest that the influence of landscape features likely plays an important role in the spatiotemporal spread of an infectious disease within wildlife populations. PMID:21197421

  17. Zinc status in human immunodeficiency virus infection

    SciTech Connect

    Walter, R.M. Jr.; Oster, M.H.; Lee, T.J.; Flynn, N.; Keen, C.L. )

    1990-01-01

    Plasma zinc and copper concentrations, erythrocyte zinc concentration, copper-zinc superoxide dismutase activity and urinary zinc concentrations were determined for control subjects and individuals with AIDS, ARC, or asymptomatic HIV infection. Significant differences among the population groups were not noted for the above parameters with the exception of plasma copper which was higher in the AIDS group than in other patient groups. These results do not support the idea that zinc deficiency is a common contributory factor of HIV infectivity or clinical expression, nor that HIV infection induces a zinc deficiency.

  18. Inhibition of Mayaro virus infection by bovine lactoferrin.

    PubMed

    Carvalho, Carlos A M; Sousa, Ivanildo P; Silva, Jerson L; Oliveira, Andréa C; Gonçalves, Rafael B; Gomes, Andre M O

    2014-03-01

    Mayaro virus (MAYV) is an arbovirus linked to several sporadic outbreaks of a highly debilitating febrile illness in many regions of South America. MAYV is on the verge of urbanization from the Amazon region and no effective antiviral intervention is available against human infections. Our aim was to investigate whether bovine lactoferrin (bLf), an iron-binding glycoprotein, could hinder MAYV infection. We show that bLf promotes a strong inhibition of virus infection with no cytotoxic effects. Monitoring the effect of bLf on different stages of infection, we observed that virus entry into the cell is the heavily compromised event. Moreover, we found that binding of bLf to the cell is highly dependent on the sulfation of glycosaminoglycans, suggesting that bLf impairs virus entry by blocking these molecules. Our findings highlight the antiviral potential of bLf and reveal an effective strategy against one of the major emerging human pathogens in the neotropics. PMID:24606707

  19. Protective effect of dietary xylitol on influenza A virus infection.

    PubMed

    Yin, Sun Young; Kim, Hyoung Jin; Kim, Hong-Jin

    2014-01-01

    Xylitol has been used as a substitute for sugar to prevent cavity-causing bacteria, and most studies have focused on its benefits in dental care. Meanwhile, the constituents of red ginseng (RG) are known to be effective in ameliorating the symptoms of influenza virus infection when they are administered orally for 14 days. In this study, we investigated the effect of dietary xylitol on influenza A virus infection (H1N1). We designed regimens containing various fractions of RG (RGs: whole extract, water soluble fraction, saponin and polysaccharide) and xylitol, and combination of xylitol with the RG fractions. Mice received the various combinations orally for 5 days prior to lethal influenza A virus infection. Almost all the mice died post challenge when xylitol or RGs were administered separately. Survival was markedly enhanced when xylitol was administered along with RGs, pointing to a synergistic effect. The effect of xylitol plus RG fractions increased with increasing dose of xylitol. Moreover, dietary xylitol along with the RG water soluble fraction significantly reduced lung virus titers after infection. Therefore, we suggest that dietary xylitol is effective in ameliorating influenza-induced symptoms when it is administered with RG fractions, and this protective effect of xylitol should be considered in relation to other diseases. PMID:24392148

  20. Descending Mediastinitis in Epstein-Barr Virus Infection

    PubMed Central

    van Driel, E. M.; Janssen, M. J. F. M.

    2015-01-01

    Our case report describes a previously healthy 34-year-old male who develops a descending mediastinitis as a complication of an Epstein-Barr virus (EBV) infection. The mediastinitis was suspected to have developed by a breakthrough of a peritonsillar abscess through the space between the alar and prevertebral space. PMID:25740774

  1. Influenza A virus and secondary bacterial infection in swine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Influenza A virus (IAV) infection alone causes significant disease characterized by respiratory distress and poor growth in pigs. Endemic strains of IAV in North America pigs consist of the subtypes H1N1, H1N2, and H3N2. These circulating strains contain the triple reassortant internal gene (TRIG) c...

  2. Aquagenic urticaria and human immunodeficiency virus infection: treatment with stanozolol.

    PubMed

    Fearfield, L A; Gazzard, B; Bunker, C B

    1997-10-01

    We report the first case of aquagenic urticaria in a patient with human immunodeficiency virus (HIV) infection. This is a rare physical urticaria not previously described in this context. The disorder proved unamenable to conventional treatment with antihistamines, but did respond dramatically to stanozolol, suggesting a novel indication for this anabolic steroid. PMID:9390343

  3. Protective Effect of Dietary Xylitol on Influenza A Virus Infection

    PubMed Central

    Yin, Sun Young; Kim, Hyoung Jin; Kim, Hong-Jin

    2014-01-01

    Xylitol has been used as a substitute for sugar to prevent cavity-causing bacteria, and most studies have focused on its benefits in dental care. Meanwhile, the constituents of red ginseng (RG) are known to be effective in ameliorating the symptoms of influenza virus infection when they are administered orally for 14 days. In this study, we investigated the effect of dietary xylitol on influenza A virus infection (H1N1). We designed regimens containing various fractions of RG (RGs: whole extract, water soluble fraction, saponin and polysaccharide) and xylitol, and combination of xylitol with the RG fractions. Mice received the various combinations orally for 5 days prior to lethal influenza A virus infection. Almost all the mice died post challenge when xylitol or RGs were administered separately. Survival was markedly enhanced when xylitol was administered along with RGs, pointing to a synergistic effect. The effect of xylitol plus RG fractions increased with increasing dose of xylitol. Moreover, dietary xylitol along with the RG water soluble fraction significantly reduced lung virus titers after infection. Therefore, we suggest that dietary xylitol is effective in ameliorating influenza-induced symptoms when it is administered with RG fractions, and this protective effect of xylitol should be considered in relation to other diseases. PMID:24392148

  4. West Nile Virus Infection among the Homeless, Houston, Texas1

    PubMed Central

    Meyer, Tamra E.; Bull, Lara M.; Holmes, Kelly Cain; Pascua, Rhia F.; Travassos da Rosa, Amelia; Gutierrez, Christian R.; Corbin, Tracie; Woodward, Jennifer L.; Taylor, Jeffrey P.; Tesh, Robert B.

    2007-01-01

    Among 397 homeless participants studied, the overall West Nile virus (WNV) seroprevalence was 6.8%. Risk factors for WNV infection included being homeless >1 year, spending >6 hours outside daily, regularly taking mosquito precautions, and current marijuana use. Public health interventions need to be directed toward this high-risk population. PMID:18257995

  5. Physiological effects of Squash vein yellowing virus infection on watermelon

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Squash vein yellowing virus (SqVYV) is the cause of viral watermelon vine decline. In this study, watermelon plants of different ages were inoculated with SqVYV to characterize the physiological response to infection and provide new insights into watermelon vine decline. Physiological responses to...

  6. The Variegate Neurological Manifestations of Varicella Zoster Virus Infection

    PubMed Central

    Nagel, Maria A.; Cohrs, Randall J.; Mahalingam, Ravi

    2014-01-01

    Varicella zoster virus (VZV) is an exclusively human neurotropic alphaherpesvirus. Primary infection causes varicella (chickenpox), after which the virus becomes latent in ganglionic neurons along the entire neuraxis. With advancing age or immunosuppression, cell-mediated immunity to VZV declines, and the virus reactivates to cause zoster (shingles), dermatomal distribution, pain, and rash. Zoster is often followed by chronic pain (postherpetic neuralgia), cranial nerve palsies, zoster paresis, vasculopathy, meningoencephalitis, and multiple ocular disorders. This review covers clinical, laboratory, and pathological features of neurological complications of VZV reactivation, including diagnostic testing to verify active VZV infection in the nervous system. Additional perspectives are provided by discussions of VZV latency, animal models to study varicella pathogenesis and immunity, and of the value of vaccination of elderly individuals to boost cell-mediated immunity to VZV and prevent VZV reactivation. PMID:23884722

  7. Current Approaches for Diagnosis of Influenza Virus Infections in Humans.

    Pu