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Sample records for neonatali viral infections

  1. INFEZIONI VIRALI CONGENITE, PERINATALI E NEONATALI VIRAL INFECTIONS OF THE FETUS AND NEWBORN INFANT

    PubMed Central

    Tremolada, Sara; Delbue, Serena; Ferrante, Pasquale

    2009-01-01

    Riassunto Alcuni virus possono essere trasmessi verticalmente da madre a figlio in seguito allo sviluppo, da parte della madre, di un’infezione primaria, ricorrente o cronica. La trasmissione materno-fetale dei virus, che può avvenire in utero (infezione congenita), durante il travaglio del parto (infezione perinatale), oppure attraverso l’allattamento (infezione postnatale), può causare aborto spontaneo, morte fetale, ritardo di crescita intrauterino, anomalie congenite e patologie neonatali o postnatali di diversa entità. Alcuni fattori di rischio sembrano influenzare l’incidenza di trasmissione materno-fetale dei virus, come ad esempio la presenza di altre infezioni virali, la carica virale materna, il tipo di infezione (primaria o ricorrente), la durata della rottura delle membrane, la modalità con cui avviene il parto, le condizioni socio-economiche e l’allattamento. Oggi è possibile prevenire la trasmissione materno-fetale di molti virus grazie all’utilizzo di vaccini, immunizzazione passiva e farmaci antivirali. Il rischio di trasmissione delle infezioni perinatali e postnatali, inoltre, può essere diminuito evitando l’allattamento o ricorrendo ad un parto cesareo. PMID:19216201

  2. Viral Infections

    MedlinePlus

    ... to fight it off. For most viral infections, treatments can only help with symptoms while you wait ... for viral infections. There are antiviral medicines to treat some viral infections. Vaccines can help prevent you ...

  3. Viral infection

    PubMed Central

    Puigdomènech, Isabel; de Armas-Rillo, Laura; Machado, José-David

    2011-01-01

    Viruses have developed different survival strategies in host cells by crossing cell-membrane compartments, during different steps of their viral life cycle. In fact, the non-regenerative viral membrane of enveloped viruses needs to encounter the dynamic cell-host membrane, during early steps of the infection process, in which both membranes fuse, either at cell-surface or in an endocytic compartment, to promote viral entry and infection. Once inside the cell, many viruses accomplish their replication process through exploiting or modulating membrane traffic, and generating specialized compartments to assure viral replication, viral budding and spreading, which also serve to evade the immune responses against the pathogen. In this review, we have attempted to present some data that highlight the importance of membrane dynamics during viral entry and replicative processes, in order to understand how viruses use and move through different complex and dynamic cell-membrane structures and how they use them to persist. PMID:21966556

  4. Viral infections and allergies.

    PubMed

    Xepapadaki, Paraskevi; Papadopoulos, Nikolaos G

    2007-01-01

    Respiratory viral infections have been implicated in the origin of, protection from and exacerbation of allergy-related symptoms in a variety of ways. Viral infections are closely linked to infantile wheezing. Severe bronchiolitis in early infancy may predispose to chronic childhood asthma as well as allergic sensitization; alternatively it could represent a marker of susceptible individuals. In contrast, repeated mild infections in early life may have a protective role in the development of asthma or atopy by driving the immune system towards Th1 responses. However, evidence on this hypothesis is not consistent as far as respiratory viruses are concerned. Several factors, including the presence of an atopic environment, timing of exposure and severity of the infection, interactively contribute to the allergy-infection relationship. In the present report, recent data on the role of viral infections in the development and progression of allergy and asthma are reviewed.

  5. Microvesicles and viral infection.

    PubMed

    Meckes, David G; Raab-Traub, Nancy

    2011-12-01

    Cells secrete various membrane-enclosed microvesicles from their cell surface (shedding microvesicles) and from internal, endosome-derived membranes (exosomes). Intriguingly, these vesicles have many characteristics in common with enveloped viruses, including biophysical properties, biogenesis, and uptake by cells. Recent discoveries describing the microvesicle-mediated intercellular transfer of functional cellular proteins, RNAs, and mRNAs have revealed additional similarities between viruses and cellular microvesicles. Apparent differences include the complexity of viral entry, temporally regulated viral expression, and self-replication proceeding to infection of new cells. Interestingly, many virally infected cells secrete microvesicles that differ in content from their virion counterparts but may contain various viral proteins and RNAs. For the most part, these particles have not been analyzed for their content or functions during viral infection. However, early studies of microvesicles (L-particles) secreted from herpes simplex virus-infected cells provided the first evidence of microvesicle-mediated intercellular communication. In the case of Epstein-Barr virus, recent evidence suggests that this tumorigenic herpesvirus also utilizes exosomes as a mechanism of cell-to-cell communication through the transfer of signaling competent proteins and functional microRNAs to uninfected cells. This review focuses on aspects of the biology of microvesicles with an emphasis on their potential contributions to viral infection and pathogenesis.

  6. [Vasculitis and viral infection].

    PubMed

    Martínez Aguilar, N E; Guido Bayardo, R; Vargas Camaño, M E; Compañ González, D; Miranda Feria, A J

    1997-01-01

    Viruses have been implicated in vasculitis. To determine activity of viral infection associated with vasculitis. 17 patients with vasculitis had been in immunological and antiviral antibodies evaluation. Twenty five healthy controls sex and age matched with hematic biometry (BH) and AA. All subjects were negative to HIV and HBV. Viral activity was demonstrated in eight patients; vascular purpura (5), Takayasu disease (1), polyarteritis nodosa (1), erythema nodosum (1). None subject of control group had IgM activity. Antibodies response of IgG in patients were of lesser intensity than in control group. 14 abnormalities in BH were found in patients and 4 in control group. Immune response in patients, measured by lymphocyte subpopulations and circulating immune complexes was abnormal. In conclusion 47% showed viral activity, but the dominant feature was abnormal immune response in 82%.

  7. Dengue viral infections

    PubMed Central

    Malavige, G; Fernando, S; Fernando, D; Seneviratne, S

    2004-01-01

    Dengue viral infections are one of the most important mosquito borne diseases in the world. They may be asymptomatic or may give rise to undifferentiated fever, dengue fever, dengue haemorrhagic fever (DHF), or dengue shock syndrome. Annually, 100 million cases of dengue fever and half a million cases of DHF occur worldwide. Ninety percent of DHF subjects are children less than 15 years of age. At present, dengue is endemic in 112 countries in the world. No vaccine is available for preventing this disease. Early recognition and prompt initiation of appropriate treatment are vital if disease related morbidity and mortality are to be limited. This review outlines aspects of the epidemiology of dengue infections, the dengue virus and its mosquito vector, clinical features and pathogenesis of dengue infections, and the management and control of these infections. PMID:15466994

  8. Immunogenetics of viral infections.

    PubMed

    Martin, Maureen P; Carrington, Mary

    2005-10-01

    The HLA class I and II genes encode molecules that lie at the heart of the acquired immune response against infectious diseases. Associations between these polymorphic loci and genetically complex infectious diseases have been historically elusive, in contrast to the more obvious HLA associations with autoimmune diseases. High resolution molecular typing of large, clinically well-defined cohorts has begun to uncover evidence for the influence of HLA diversity on diseases of viral etiology, such as those caused by HIV-1, hepatitis B virus, hepatitis C virus and human papilloma virus. Combinations of HLA and KIR also appear to affect outcome to viral infection, supporting a role for HLA class I diversity in the innate immune response in addition to the acquired immune response.

  9. Saliva and viral infections.

    PubMed

    Corstjens, Paul L A M; Abrams, William R; Malamud, Daniel

    2016-02-01

    Over the last 10 years there have been only a handful of publications dealing with the oral virome, which is in contrast to the oral microbiome, an area that has seen considerable interest. Here, we survey viral infections in general and then focus on those viruses that are found in and/or are transmitted via the oral cavity; norovirus, rabies, human papillomavirus, Epstein-Barr virus, herpes simplex viruses, hepatitis C virus, and HIV. Increasingly, viral infections have been diagnosed using an oral sample (e.g. saliva mucosal transudate or an oral swab) instead of blood or urine. The results of two studies using a rapid and semi-quantitative lateral flow assay format demonstrating the correlation of HIV anti-IgG/sIgA detection with saliva and serum samples are presented. When immediate detection of infection is important, point-of-care devices that obtain a non-invasive sample from the oral cavity can be used to provide a first line diagnosis to assist in determining appropriate counselling and therapeutic path for an increasing number of diseases.

  10. Viral infections of the face.

    PubMed

    Avci, Oktay; Ertam, Ilgen

    2014-01-01

    Viral infections affecting the face may cause significant morbidity, cosmetic disfigurement, and psychological distress. The success of therapy needs whole and correct evaluation of the clinical signs and symptoms. Some viruses such as Papillomaviridae, Herpesviridae, and Polyomaviridae primarily infect the facial skin, whereas others affect the face infrequently, as in parapox virus infections. Sometimes, involvement of the face can be a part of more generalized eruption and systemic symptoms in viral infections caused by Todaviridae, Flaviviridae, Arenaviridiae, and Flaviviridae. Clinical diagnosis can be challenging in various viral diseases when they occur in nonendemic geographic areas. The objective of this review was to concentrate on epidemiologic and clinical characteristics of the viral illnesses with facial skin involvement.

  11. Viral infection, inflammation and schizophrenia

    PubMed Central

    Kneeland, Rachel E.; Fatemi, S. Hossein

    2012-01-01

    Schizophrenia is a severe neurodevelopmental disorder with genetic and environmental etiologies. Prenatal viral/bacterial infections and inflammation play major roles in the genesis of schizophrenia. In this review, we describe a viral model of schizophrenia tested in mice whereby the offspring of mice prenatally infected with influenza at E7, E9, E16, and E18 show significant gene, protein, and brain structural abnormalities postnatally. Similarly, we describe data on rodents exposed to bacterial infection or injected with a synthetic viral mimic (PolyI:C) also demonstrating brain structural and behavioral abnormalities. Moreover, human serologic data has been indispensible in supporting the viral theory of schizophrenia. Individuals born seropositive for bacterial and viral agents are at a significantly elevated risk of developing schizophrenia. While the specific mechanisms of prenatal viral/bacterial infections and brain disorder are unclear, recent findings suggest that the maternal inflammatory response may be associated with fetal brain injury. Preventive and therapeutic treatment options are also proposed. This review presents data related to epidemiology, human serology, and experimental animal models which support the viral model of schizophrenia. PMID:22349576

  12. Viral infection, inflammation and schizophrenia.

    PubMed

    Kneeland, Rachel E; Fatemi, S Hossein

    2013-04-05

    Schizophrenia is a severe neurodevelopmental disorder with genetic and environmental etiologies. Prenatal viral/bacterial infections and inflammation play major roles in the genesis of schizophrenia. In this review, we describe a viral model of schizophrenia tested in mice whereby the offspring of mice prenatally infected with influenza at E7, E9, E16, and E18 show significant gene, protein, and brain structural abnormalities postnatally. Similarly, we describe data on rodents exposed to bacterial infection or injected with a synthetic viral mimic (PolyI:C) also demonstrating brain structural and behavioral abnormalities. Moreover, human serologic data has been indispensible in supporting the viral theory of schizophrenia. Individuals born seropositive for bacterial and viral agents are at a significantly elevated risk of developing schizophrenia. While the specific mechanisms of prenatal viral/bacterial infections and brain disorder are unclear, recent findings suggest that the maternal inflammatory response may be associated with fetal brain injury. Preventive and therapeutic treatment options are also proposed. This review presents data related to epidemiology, human serology, and experimental animal models which support the viral model of schizophrenia. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Viral infections of nonhuman primates.

    PubMed

    Kalter, S S; Heberling, R L; Cooke, A W; Barry, J D; Tian, P Y; Northam, W J

    1997-10-01

    Approximately 53,000 serologic tests and viral isolation studies were performed on 1,700 nonhuman primate specimens for evidence of past and/or current viral infection. Information, other than the requested test, generally was not provided with the specimen. This lack of information does not permit any attempt at interpretation of results. Requested testing included a large number of diverse viral agents in approximately 40 primate species. The resulting data are in keeping with those of previous studies and offer an insight into the needs of colony management, as well as some general information on the overall frequency of infection with the indicated viruses. Inasmuch as the results represent testing of single specimens, they are not to be construed as "diagnostic," and simply indicate past infection as represented by the presence of antibody in the test animal. Viral isolation results are listed, and the number of positive results versus the number of animals tested emphasizes the limitations of the procedure. Investigations such as these continue to assist in the maintenance of healthy nonhuman primate colonies. This information also supports continued use of nonhuman primates for research in human viral infections and may be helpful in terms of animal selection for use in xenotransplants.

  14. Viral infections of rabbits.

    PubMed

    Kerr, Peter J; Donnelly, Thomas M

    2013-05-01

    Viral diseases of rabbits have been used historically to study oncogenesis (e.g. rabbit fibroma virus, cottontail rabbit papillomavirus) and biologically to control feral rabbit populations (e.g. myxoma virus). However, clinicians seeing pet rabbits in North America infrequently encounter viral diseases although myxomatosis may be seen occasionally. The situation is different in Europe and Australia, where myxomatosis and rabbit hemorrhagic disease are endemic. Advances in epidemiology and virology have led to detection of other lapine viruses that are now recognized as agents of emerging infectious diseases. Rabbit caliciviruses, related to rabbit hemorrhagic disease, are generally avirulent, but lethal variants are being identified in Europe and North America. Enteric viruses including lapine rotavirus, rabbit enteric coronavirus and rabbit astrovirus are being acknowledged as contributors to the multifactorial enteritis complex of juvenile rabbits. Three avirulent leporid herpesviruses are found in domestic rabbits. A fourth highly pathogenic virus designated leporid herpesvirus 4 has been described in Canada and Alaska. This review considers viruses affecting rabbits by their clinical significance. Viruses of major and minor clinical significance are described, and viruses of laboratory significance are mentioned. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Autistic disorder and viral infections.

    PubMed

    Libbey, Jane E; Sweeten, Thayne L; McMahon, William M; Fujinami, Robert S

    2005-02-01

    Autistic disorder (autism) is a behaviorally defined developmental disorder with a wide range of behaviors. Although the etiology of autism is unknown, data suggest that autism results from multiple etiologies with both genetic and environmental contributions, which may explain the spectrum of behaviors seen in this disorder. One proposed etiology for autism is viral infection very early in development. The mechanism, by which viral infection may lead to autism, be it through direct infection of the central nervous system (CNS), through infection elsewhere in the body acting as a trigger for disease in the CNS, through alteration of the immune response of the mother or offspring, or through a combination of these, is not yet known. Animal models in which early viral infection results in behavioral changes later in life include the influenza virus model in pregnant mice and the Borna disease virus model in newborn Lewis rats. Many studies over the years have presented evidence both for and against the association of autism with various viral infections. The best association to date has been made between congenital rubella and autism; however, members of the herpes virus family may also have a role in autism. Recently, controversy has arisen as to the involvement of measles virus and/or the measles, mumps, rubella (MMR) vaccine in the development of autism. Biological assays lend support to the association between measles virus or MMR and autism whereas epidemiologic studies show no association between MMR and autism. Further research is needed to clarify both the mechanisms whereby viral infection early in development may lead to autism and the possible involvement of the MMR vaccine in the development of autism.

  16. Pediatric Asthma and Viral Infection.

    PubMed

    Garcia-Garcia, M Luz; Calvo Rey, Cristina; Del Rosal Rabes, Teresa

    2016-05-01

    Respiratory viral infections, particularly respiratory syncytial virus (RSV) and rhinovirus, are the most importance risk factors for the onset of wheezing in infants and small children. Bronchiolitis is the most common acute respiratory infection in children under 1year of age, and the most common cause of hospitalization in this age group. RSV accounts for approximately 70% of all these cases, followed by rhinovirus, adenovirus, metapneumovirus and bocavirus. The association between bronchiolitis caused by RSV and the development of recurrent wheezing and/or asthma was first described more than 40years ago, but it is still unclear whether bronchiolitis causes chronic respiratory symptoms, or if it is a marker for children with a genetic predisposition for developing asthma in the medium or long term. In any case, sufficient evidence is available to corroborate the existence of this association, which is particularly strong when the causative agent of bronchiolitis is rhinovirus. The pathogenic role of respiratory viruses as triggers for exacerbations in asthmatic patients has not been fully characterized. However, it is clear that respiratory viruses, and in particular rhinovirus, are the most common causes of exacerbation in children, and some type of respiratory virus has been identified in over 90% of children hospitalized for an episode of wheezing. Changes in the immune response to viral infections in genetically predisposed individuals are very likely to be the main factors involved in the association between viral infection and asthma.

  17. Recycling Endosomes and Viral Infection

    PubMed Central

    Vale-Costa, Sílvia; Amorim, Maria João

    2016-01-01

    Many viruses exploit specific arms of the endomembrane system. The unique composition of each arm prompts the development of remarkably specific interactions between viruses and sub-organelles. This review focuses on the viral–host interactions occurring on the endocytic recycling compartment (ERC), and mediated by its regulatory Ras-related in brain (Rab) GTPase Rab11. This protein regulates trafficking from the ERC and the trans-Golgi network to the plasma membrane. Such transport comprises intricate networks of proteins/lipids operating sequentially from the membrane of origin up to the cell surface. Rab11 is also emerging as a critical factor in an increasing number of infections by major animal viruses, including pathogens that provoke human disease. Understanding the interplay between the ERC and viruses is a milestone in human health. Rab11 has been associated with several steps of the viral lifecycles by unclear processes that use sophisticated diversified host machinery. For this reason, we first explore the state-of-the-art on processes regulating membrane composition and trafficking. Subsequently, this review outlines viral interactions with the ERC, highlighting current knowledge on viral-host binding partners. Finally, using examples from the few mechanistic studies available we emphasize how ERC functions are adjusted during infection to remodel cytoskeleton dynamics, innate immunity and membrane composition. PMID:27005655

  18. Viral Infection in Renal Transplant Recipients

    PubMed Central

    Cukuranovic, Jovana; Ugrenovic, Sladjana; Jovanovic, Ivan; Visnjic, Milan; Stefanovic, Vladisav

    2012-01-01

    Viruses are among the most common causes of opportunistic infection after transplantation. The risk for viral infection is a function of the specific virus encountered, the intensity of immune suppression used to prevent graft rejection, and other host factors governing susceptibility. Although cytomegalovirus is the most common opportunistic pathogen seen in transplant recipients, numerous other viruses have also affected outcomes. In some cases, preventive measures such as pretransplant screening, prophylactic antiviral therapy, or posttransplant viral monitoring may limit the impact of these infections. Recent advances in laboratory monitoring and antiviral therapy have improved outcomes. Studies of viral latency, reactivation, and the cellular effects of viral infection will provide clues for future strategies in prevention and treatment of viral infections. This paper will summarize the major viral infections seen following transplant and discuss strategies for prevention and management of these potential pathogens. PMID:22654630

  19. Long noncoding RNAs in viral infections

    PubMed Central

    Fortes, Puri; Morris, Kevin

    2015-01-01

    Viral infections induce strong modifications in the cell transcriptome. Among the RNAs whose expression is altered by infection are long noncoding RNAs (lncRNAs). LncRNAs are transcripts with potential to function as RNA molecules. Infected cells may express viral lncRNAs, cellular lncRNAs and chimeric lncRNAs formed by viral and cellular sequences. Some viruses express viral lncRNAs whose function is essential for viral viability. They are transcribed by polymerase II or III and some of them can be processed by unique maturation steps performed by host cell machineries. Some viral lncRNAs control transcription, stability or translation of cellular and viral genes. Surprisingly, similar functions can be exerted by cellular lncRNAs induced by infection. Expression of cellular lncRNAs may be altered in response to viral replication or viral protein expression. However, many cellular lncRNAs respond to the antiviral pathways induced by infection. In fact, many lncRNAs function as positive or negative regulators of the innate antiviral response. Our current knowledge about the identity and function of lncRNAs in infected cells is very limited. However, research into this field has already helped in the identification of novel cellular pathways and may help in the development of therapeutic tools for the treatment of viral infections, autoimmune diseases, neurological disorders and cancer. PMID:26454188

  20. Mosquito defense strategies against viral infection

    PubMed Central

    Cheng, Gong; Liu, Yang; Wang, Penghua; Xiao, Xiaoping

    2015-01-01

    Mosquito-borne viral diseases are a major concern of global health and result in significant economic losses in many countries. As natural vectors, mosquitoes are very permissive to and allow systemic and persistent arbovirus infection. Intriguingly, persistent viral propagation in mosquito tissues neither results in dramatic pathological sequelae nor impairs the vectorial behavior or lifespan, indicating that mosquitoes have evolved mechanisms to tolerate persistent infection and developed efficient antiviral strategies to restrict viral replication to non-pathogenic levels. Here, we provide an overview of recent progress in understanding mosquito antiviral immunity and advances in the strategies by which mosquitoes control viral infection in specific tissues. PMID:26626596

  1. Membrane dynamics associated with viral infection.

    PubMed

    de Armas-Rillo, Laura; Valera, María-Soledad; Marrero-Hernández, Sara; Valenzuela-Fernández, Agustín

    2016-05-01

    Viral replication and spreading are fundamental events in the viral life cycle, accounting for the assembly and egression of nascent virions, events that are directly associated with viral pathogenesis in target hosts. These processes occur in cellular compartments that are modified by specialized viral proteins, causing a rearrangement of different cell membranes in infected cells and affecting the ER, mitochondria, Golgi apparatus, vesicles and endosomes, as well as processes such as autophagic membrane flux. In fact, the activation or inhibition of membrane trafficking and other related activities are fundamental to ensure the adequate replication and spreading of certain viruses. In this review, data will be presented that support the key role of membrane dynamics in the viral cycle, especially in terms of the assembly, egression and infection processes. By defining how viruses orchestrate these events it will be possible to understand how they successfully complete their route of infection, establishing viral pathogenesis and provoking disease.

  2. Snapshots: Chromatin Control of Viral Infection

    PubMed Central

    Knipe, David M.; Lieberman, Paul M.; Jung, Jae U.; McBride, Alison A.; Morris, Kevin V.; Ott, Melanie; Margolis, David; Nieto, Amelia; Nevels, Michael; Parks, Robin J.; Kristie, Thomas M.

    2012-01-01

    Like their cellular host counterparts, many invading viral pathogens must contend with, modulate, and utilize the host cell’s chromatin machinery to promote efficient lytic infection or control persistent-latent states. While not intended to be comprehensive, this review represents a compilation of conceptual snapshots of the dynamic interplay of viruses with the chromatin environment. Contributions focus on chromatin dynamics during infection, viral circumvention of cellular chromatin repression, chromatin organization of large DNA viruses, tethering and persistence, viral interactions with cellular chromatin modulation machinery, and control of viral latency-reactivation cycles. PMID:23217624

  3. Iron withholding: a defense against viral infections.

    PubMed

    Weinberg, E D

    1996-10-01

    A variety of laboratory and clinical investigations during the past 15 years have observed that one of the dangers of excessive iron is its ability to favor animal viral infections. The metal is essential for host cell synthesis of virions and can also impair defense cell function and increase oxidative stress. In both animal models and humans, viral infections cause upregulation of the iron withholding defense system. Factors that suppress the system enhance viral progression; factors that strengthen the system augment host defense. Procedures designed to reinforce the system are being developed and tested; some of these may become useful adjuncts in prevention and management of viral diseases.

  4. Neutrophil in Viral Infections, Friend or Foe?

    PubMed Central

    Drescher, Brandon; Bai, Fengwei

    2012-01-01

    Polymorphonuclear leukocytes or neutrophils are the first immune cells to the site of injury and microbial infection. Neutrophils are crucial players in controlling bacterial and fungal infections, and in particular secondary infections, by phagocytosis, degranulation and neutrophil extracellular traps (NETs). While neutrophils have been shown to play important roles in viral pathogenesis, there is a lack of detailed investigation. In this article, we will review recent progresses toward understanding the role of neutrophils in viral pathogenesis. PMID:23178588

  5. Oxygen tension level and human viral infections.

    PubMed

    Morinet, Frédéric; Casetti, Luana; François, Jean-Hugues; Capron, Claude; Pillet, Sylvie

    2013-09-01

    The role of oxygen tension level is a well-known phenomenon that has been studied in oncology and radiotherapy since about 60 years. Oxygen tension may inhibit or stimulate propagation of viruses in vitro as well as in vivo. In turn modulating oxygen metabolism may constitute a novel approach to treat viral infections as an adjuvant therapy. The major transcription factor which regulates oxygen tension level is hypoxia-inducible factor-1 alpha (HIF-1α). Down-regulating the expression of HIF-1α is a possible method in the treatment of chronic viral infection such as human immunodeficiency virus infection, chronic hepatitis B and C viral infections and Kaposi sarcoma in addition to classic chemotherapy. The aim of this review is to supply an updating concerning the influence of oxygen tension level in human viral infections and to evoke possible new therapeutic strategies regarding this environmental condition.

  6. Illuminating viral infections in the nervous system

    PubMed Central

    McGavern, Dorian B.; Kang, Silvia S.

    2016-01-01

    Viral infections are a major cause of human disease. Although most viruses replicate in peripheral tissues, some have developed unique strategies to move into the nervous system, where they establish acute or persistent infections. Viral infections in the central nervous system (CNS) can alter homeostasis, induce neurological dysfunction and result in serious, potentially life-threatening inflammatory diseases. This Review focuses on the strategies used by neurotropic viruses to cross the barrier systems of the CNS and on how the immune system detects and responds to viral infections in the CNS. A special emphasis is placed on immune surveillance of persistent and latent viral infections and on recent insights gained from imaging both protective and pathogenic antiviral immune responses. PMID:21508982

  7. Bacterial and viral infections associated with influenza.

    PubMed

    Joseph, Carol; Togawa, Yu; Shindo, Nahoko

    2013-09-01

    Influenza-associated bacterial and viral infections are responsible for high levels of morbidity and death during pandemic and seasonal influenza episodes. A review was undertaken to assess and evaluate the incidence, epidemiology, aetiology, clinical importance and impact of bacterial and viral co-infection and secondary infection associated with influenza. A review was carried out of published articles covering bacterial and viral infections associated with pandemic and seasonal influenza between 1918 and 2009 (and published through December 2011) to include both pulmonary and extra-pulmonary infections. While pneumococcal infection remains the predominant cause of bacterial pneumonia, the review highlights the importance of other co- and secondary bacterial and viral infections associated with influenza, and the emergence of newly identified dual infections associated with the 2009 H1N1 pandemic strain. Severe influenza-associated pneumonia is often bacterial and will necessitate antibiotic treatment. In addition to the well-known bacterial causes, less common bacteria such as Legionella pneumophila may also be associated with influenza when new influenza strains emerge. This review should provide clinicians with an overview of the range of bacterial and viral co- or secondary infections that could present with influenza illness.

  8. Severe Viral Infections and Primary Immunodeficiencies

    PubMed Central

    Cohen, Jeffrey I.

    2011-01-01

    Patients with severe viral infections are often not thoroughly evaluated for immunodeficiencies. In this review, we summarize primary immunodeficiencies that predispose individuals to severe viral infections. Some immunodeficiencies enhance susceptibility to disease with a specific virus or family of viruses, whereas others predispose to diseases with multiple viruses in addition to disease with other microbes. Although the role of cytotoxic T cells in controlling viral infections is well known, a number of immunodeficiencies that predispose to severe viral diseases have recently been ascribed to defects in the Toll-like receptor–interferon signaling pathway. These immunodeficiencies are rare, but it is important to identify them both for prognostic information and for genetic counseling. Undoubtedly, additional mutations in proteins in the innate and adaptive arms of the immune system will be identified in the future, which will reveal the importance of these proteins in controlling infections caused by viruses and other pathogens. PMID:21960712

  9. Drug Use and Viral Infections (HIV, Hepatitis)

    MedlinePlus

    ... virus can pass it to their baby during pregnancy, whether or not they use drugs. The viral infections of greatest concern related to drug use are HIV and hepatitis. People can reduce their risk of getting or ...

  10. Oxygen tension level and human viral infections

    SciTech Connect

    Morinet, Frédéric; Casetti, Luana; François, Jean-Hugues; Capron, Claude; Pillet, Sylvie

    2013-09-15

    The role of oxygen tension level is a well-known phenomenon that has been studied in oncology and radiotherapy since about 60 years. Oxygen tension may inhibit or stimulate propagation of viruses in vitro as well as in vivo. In turn modulating oxygen metabolism may constitute a novel approach to treat viral infections as an adjuvant therapy. The major transcription factor which regulates oxygen tension level is hypoxia-inducible factor-1 alpha (HIF-1α). Down-regulating the expression of HIF-1α is a possible method in the treatment of chronic viral infection such as human immunodeficiency virus infection, chronic hepatitis B and C viral infections and Kaposi sarcoma in addition to classic chemotherapy. The aim of this review is to supply an updating concerning the influence of oxygen tension level in human viral infections and to evoke possible new therapeutic strategies regarding this environmental condition. - Highlights: • Oxygen tension level regulates viral replication in vitro and possibly in vivo. • Hypoxia-inducible factor 1 (HIF-1α) is the principal factor involved in Oxygen tension level. • HIF-1α upregulates gene expression for example of HIV, JC and Kaposi sarcoma viruses. • In addition to classical chemotherapy inhibition of HIF-1α may constitute a new track to treat human viral infections.

  11. Respiratory Viral Infections in Chronic Lung Diseases.

    PubMed

    Britto, Clemente J; Brady, Virginia; Lee, Seiwon; Dela Cruz, Charles S

    2017-03-01

    Chronic lung diseases, such as chronic obstructive pulmonary disease (COPD), asthma, cystic fibrosis (CF) and interstitial lung diseases (ILD), affect many individuals worldwide. Patients with these chronic lung diseases are susceptible to respiratory lung infections and some of these viral infections can contribute to disease pathogenesis. This review highlights the associations of lung infections and the respective chronic lung diseases and how infection in the different lung diseases affects disease exacerbation and progression. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Viral interaction with molecular chaperones: role in regulating viral infection.

    PubMed

    Xiao, Allen; Wong, Jerry; Luo, Honglin

    2010-07-01

    As essential effectors in protein quality control, molecular chaperones serve as the primary checkpoint to assist proper protein folding and prevent misfolded proteins from denaturation and aggregation. In addition, chaperones can function to direct terminally misfolded proteins to the proteolytic system for degradation. Viruses rely on host cell machineries for productive infection. Like for many other processes, various viruses have been shown to evolve mechanisms to utilize or subvert the host protein quality control machinery to support the completion of their life cycle. Furthermore, recent studies suggest that some viruses encode for their own chaperone-like proteins to enhance their infectivity. This review summarizes the current understanding of the interplay between molecular chaperones and viral proteins, highlights the chaperone activities of a number of viral proteins, and discusses potential antiviral therapeutic strategies targeting the virus-chaperone interactions.

  13. [Obesity development associated with viral infections].

    PubMed

    Jaworowska, Agnieszka; Bazylak, Grzegorz

    2006-01-01

    This overview of the significance of viral infections in the development of human obesity is presented within context of the commonly recognized obesity risk factors, including the personal and public health consequences of obesity in various countries. In addition, the results of past and recently published studies on the recognition of six taxonomically different viruses which can undoubtedly be associated with obesity progression in some species of animals are summarized. More attention is focused on the results of preliminary epidemiological studies indicating that human infection by the avian adenovirus SMAM-1 or the human adenovirus Ad-36 can be objectively related to symptoms, prevalence, and complications of obesity in some adult men. Proposed pathogenic pathways involved in the observed cases of viral infection-dependent obesity in animals and humans are also briefly described. Urgent implementation of high-throughput diagnostics procedures is advised to extend viral infection-oriented modes of prevention, recognition, and therapy of obesity currently available in modern societies.

  14. Fish viral infections in northwest of Spain.

    PubMed

    Ledo, A; Lupiani, B; Dopazo, C P; Toranzo, A E; Barja, J L

    1990-06-01

    During a three years survey, a total of 149 samples from 20 farms of rainbow trout, salmon and turbot were examined for the presence of virus with the purpose to study the viral infections affecting cultured fish and their incidence in the fishfarms of Northwestern Spain. Infectious pancreatic necrosis virus (IPNV) was the only viral agent isolated from salmonid fish. Fry and fingerlings of trout showed the highest infection rate (24%). This virus was not detected in broodstock or embryonated eggs, although it was isolated from ovaric and seminal fluids and from juvenile carriers. From 24 samples of salmon analyzed, IPNV was only detected in one sample of juveniles. Examination of turbot led the isolation of a new virus belonging to the reoviridae family, which affected to the ongrowing population. All of the IPNV tested belonged to serotype Sp regardless of the origin of the trout stocks. During the monitorization of imported embryonated eggs, no virus was detected from any of the samples. However, in some case, IPNV was isolated when testing the fry obtained in our laboratory from those samples of imported eggs. Our findings indicate that: i) the analysis of fingerlings increase the probability to detect viral infections allowing us an optimal control of importations, and ii) most of the viral infections of fish take place in the own fish farms. The detection of mixed viral and bacterial infections emphasize the importance of carrying out an integral microbiological analysis to determine the causal agent(s) of fish mortalities.

  15. Lactoferrin for prevention of common viral infections.

    PubMed

    Wakabayashi, Hiroyuki; Oda, Hirotsugu; Yamauchi, Koji; Abe, Fumiaki

    2014-11-01

    Although lactoferrin has many biological functions, the host-protective effects against pathogenic microorganisms including bacteria, fungi, and viruses are regarded as one of the most important. Here, we review research on the protective role of lactoferrin administration against common viral infections. Many studies have shown the in vitro antiviral activity of lactoferrin against viral pathogens that cause common infections such as the common cold, influenza, gastroenteritis, summer cold, and herpes, where lactoferrin inhibits mainly viral attachment to the target cells. Recently, studies indicating the in vivo protective effects of lactoferrin by oral administration against common viral infections have been increasing. For instance, norovirus is an extremely important emerging human pathogen that causes a majority of gastroenteritis outbreaks worldwide that may be a target candidate for lactoferrin. Lactoferrin consumption reduced the incidence of noroviral gastroenteritis in children and a similar effect was observed in a wide range of ages in a preliminary survey. A recent in vitro study reported that lactoferrin inhibits both cellular attachment of the murine norovirus, a virus closely-related to the human norovirus, and viral replication in the cells by inducing antiviral cytokines interferon (IFN)-α/β. Lactoferrin administration also enhances NK cell activity and Th1 cytokine responses, which lead to protection against viral infections. In conclusion, lactoferrin consumption may protect the host from viral infections through inhibiting the attachment of a virus to the cells, replication of the virus in the cells, and enhancement of systemic immune functions. Copyright © 2014 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  16. Cell cycle regulation during viral infection.

    PubMed

    Bagga, Sumedha; Bouchard, Michael J

    2014-01-01

    To replicate their genomes in cells and generate new progeny, viruses typically require factors provided by the cells that they have infected. Subversion of the cellular machinery that controls replication of the infected host cell is a common activity of many viruses. Viruses employ different strategies to deregulate cell cycle checkpoint controls and modulate cell proliferation pathways. A number of DNA and RNA viruses encode proteins that target critical cell cycle regulators to achieve cellular conditions that are beneficial for viral replication. Many DNA viruses induce quiescent cells to enter the cell cycle; this is thought to increase pools of deoxynucleotides and thus, facilitate viral replication. In contrast, some viruses can arrest cells in a particular phase of the cell cycle that is favorable for replication of the specific virus. Cell cycle arrest may inhibit early cell death of infected cells, allow the cells to evade immune defenses, or help promote virus assembly. Although beneficial for the viral life cycle, virus-mediated alterations in normal cell cycle control mechanisms could have detrimental effects on cellular physiology and may ultimately contribute to pathologies associated with the viral infection, including cell transformation and cancer progression and maintenance. In this chapter, we summarize various strategies employed by DNA and RNA viruses to modulate the replication cycle of the virus-infected cell. When known, we describe how these virus-associated effects influence replication of the virus and contribute to diseases associated with infection by that specific virus.

  17. [Emerging viral zoonoses: hantavirus infections].

    PubMed

    Enria, D A M; Levis, S C

    2004-08-01

    Hantaviruses are rodent-borne agents belonging to the Bunyaviridae family. These viruses, which are found throughout Europe, Asia and the Americas, are maintained by different species of rodents, in which they produce chronic, inapparent infections. Humans become infected through contact with urine, saliva or faeces from infected rodents, mainly via the aerosol route. In humans, clinical disease occurs in the form of two major syndromes: haemorrhagic fever with renal syndrome (HFRS) or hantavirus pulmonary syndrome (HPS). Haemorrhagic fever with renal syndrome mainly occurs in Europe and Asia and HPS has only ever been reported in the Americas. Person-to-person transmission of hantaviruses, although uncommon, was described during an outbreak of HPS in southern Argentina. Most epidemics of HFRS and HPS occur in areas with large populations of rodents that have a relatively high prevalence of infection.

  18. Cytoplasmic RNA Granules and Viral Infection.

    PubMed

    Tsai, Wei-Chih; Lloyd, Richard E

    2014-11-01

    RNA granules are dynamic cellular structures essential for proper gene expression and homeostasis. The two principal types of cytoplasmic RNA granules are stress granules, which contain stalled translation initiation complexes, and processing bodies (P bodies), which concentrate factors involved in mRNA degradation. RNA granules are associated with gene silencing of transcripts; thus, viruses repress RNA granule functions to favor replication. This article discusses the breadth of viral interactions with cytoplasmic RNA granules, focusing on mechanisms that modulate the functions of RNA granules and that typically promote viral replication. Currently, mechanisms for virus manipulation of RNA granules can be loosely grouped into three nonexclusive categories: (a) cleavage of key RNA granule factors, (b) regulation of PKR activation, and (c) co-opting of RNA granule factors for new roles in viral replication. Viral modulation of RNA granules supports productive infection by inhibiting their gene-silencing functions and counteracting their role in linking stress sensing with innate immune activation.

  19. [Viral infections of human central nervous system].

    PubMed

    Agut, Henri

    2016-01-01

    The viruses that can infect the central nervous system of humans are numerous and form a heterogeneous group with respect to their structural, functional and epidemiological properties. The pathophysiological mechanisms leading to associated neurological diseases, mainly meningitis and encephalitis, also are complex and often intertwined. Overall, neurological clinical symptoms correspond either to acute viral diseases associated with primary infections or to acute, subacute or chronic diseases associated with persistent viral infections. The frequent severity of the clinical situation requires in all cases the practice of virological diagnosis for which the PCR techniques applied to cerebrospinal fluid samples occupy a prominent place. The severity of clinical manifestations justifies the use of prophylactic vaccination when available and antiviral treatment as soon as the causative virus is identified or suspected.

  20. Three-Dimensional Imaging of Viral Infections.

    PubMed

    Risco, Cristina; de Castro, Isabel Fernández; Sanz-Sánchez, Laura; Narayan, Kedar; Grandinetti, Giovanna; Subramaniam, Sriram

    2014-11-01

    Three-dimensional (3D) imaging technologies are beginning to have significant impact in the field of virology, as they are helping us understand how viruses take control of cells. In this article we review several methodologies for 3D imaging of cells and show how these technologies are contributing to the study of viral infections and the characterization of specialized structures formed in virus-infected cells. We include 3D reconstruction by transmission electron microscopy (TEM) using serial sections, electron tomography, and focused ion beam scanning electron microscopy (FIB-SEM). We summarize from these methods selected contributions to our understanding of viral entry, replication, morphogenesis, egress and propagation, and changes in the spatial architecture of virus-infected cells. In combination with live-cell imaging, correlative microscopy, and new techniques for molecular mapping in situ, the availability of these methods for 3D imaging is expected to provide deeper insights into understanding the structural and dynamic aspects of viral infection.

  1. Virion-targeted viral inactivation: new therapy against viral infection.

    PubMed

    Okui, N; Kitamura, Y; Kobayashi, N; Sakuma, R; Ishikawa, T; Kitamura, T

    2001-01-01

    Acquired immune deficiency syndrome (AIDS) is resistant to all current therapy. Gene therapy is an attractive alternative or additive to current, unsatisfactory AIDS therapy. To develop an antiviral molecule targeting viral integrase (HIV IN), we generated a single-chain antibody, termed scAb, which interacted with human immunodeficiency virus type 1 (HIV-1) IN and inhibited virus replication at the integration step when expressed intracellularly. To reduce infectivity from within the virus particles, we made expression plasmids (pC-scAbE-Vpr, pC-scAbE-CA, and pC-scAbE-WXXF), which expressed the anti-HIV IN scAb fused to the N-terminus of HIV-1-associated accessory protein R (Vpr), capsid protein (CA), and specific binding motif to Vpr (WXXF), respectively. All fusion proteins were tagged with a nine-amino acid peptide derived from influenza virus hemagglutinin (HA) at the C terminus. The fusion molecules, termed scAbE-Vpr, scAbE-CA, and scAbE-WXXF, interacted specifically with HIV IN immobilized on a nitrocellulose membrane. Immunoblot analysis showed that scAbE-Vpr, scAbE-CA, and scAbE-WXXF were incorporated into the virions produced by cotransfection of 293T cells with HIV-1 infectious clone DNA (pLAI) and pC-scAbE-Vpr, pC-scAbE-WXXF. A multinuclear activation galactosidase indicator (MAGI) assay revealed that the virions released from 293T cells cotransfected with pLAI and pC-scAbE-Vpr, pC-scAbE-WXXF had as little 1000-fold of the infectivity of the control wild-type virions, which were produced from the 293T cells transfected with pLAI alone. Furthermore, the virions produced from the 293T cells cotransfected with pLAI and an scAb expression vector (pC-scAb) showed only 1% of the infectivity of the control HIV-1 in a MAGI assay, although scAb was not incorporated into the virions. In either instance, the total quantity of the progeny virions released from the transfected 293T cells and the patterns of the virion proteins were hardly affected by the presence of

  2. Visualizing viral transport and host infection

    NASA Astrophysics Data System (ADS)

    Son, Kwangmin; Guasto, Jeffrey; Cubillos-Ruiz, Andres; Sullivan, Matthew; Stocker, Roman; MIT Team

    2013-11-01

    A virus is a non-motile infectious agent that can only replicate inside a living host. They consist of a <100 nm diameter capsid which houses their DNA, and a <20 nm diameter tail used to inject DNA to the host, which are classified into three different morphologies by the tail type: short tail (~ 10 nm, podovirus), rigid contractile tail (~ 100 nm, myovirus), or flexible noncontractile tail (~ 300 nm, siphovirus). Combining microfluidics with epifluorescent microscopy, we studied the simultaneous diffusive transport governing the initial encounter and ultimately the infection of a non-motile cyanobacteria host (~ 1 μm prochlorococcus) and their viral (phage) counterparts in real time. This methodology allows us to quantify the virus-host encounter/adsorption dynamics and subsequently the effectiveness of various tail morphologies for viral infection. Viral transport and the role of viral morphology in host-virus interactions are critical to our understanding of both ecosystem dynamics and human health, as well as to the evolution of virus morphology.

  3. The Role of Immunophilins in Viral Infection

    PubMed Central

    Hopkins, Sam; Gallay, Philippe A.

    2015-01-01

    Background Tremendous progress has been made in the past 20 years in understanding the roles played by immunophilins, and in particular the cyclophilins, in supporting the replication cycles of human viruses. A growing body of genetic and biochemical evidence and data from clinical trials confirms that cyclophilins are essential cofactors that contribute to establishing a permissive environment within the host cell that supports the replication of HIV-1 and HCV. Cyclophilin A regulates HIV-1 replication kinetics and infectivity, modulates sensitivity to host restriction factors, and cooperates in the transit of the pre-integration complex into the nucleus of infected cells. Cyclophilin A is an essential cofactor whose expression supports HCV-specific RNA replication in human hepatocytes. General Significance Peptidyl-prolyl isomerase inhibitors have been used in clinical trials to validate cyclophilins as antiviral targets for the treatment of HIV-1 and Chronic Hepatitis C virus infection and as molecular probes to identify the roles played by immunophilins in supporting the replication cycles of human viruses. Scope of Review This review summarizes emerging research that defines the functions of immunophilins in supporting the replication cycles of HIV-1, HCV, HBV, coronaviruses, and other viral pathogens and describes new information that suggests a role for immunophilins in regulating innate immune responses against chronic viral infection. Major Conclusions The dependence on cyclophilins by evolutionarily distinct viruses for accomplishing various steps in replication such as viral entry, initiation of genomic nucleic acid replication, viral genome uncoating, nuclear import and nuclear entry, emphasizes the potential of cyclophilin inhibitors as therapeutic agents. PMID:25445708

  4. Cutaneous viral infections in organ transplant patients.

    PubMed

    Piaserico, S; Sandini, E; Peserico, A; Alaibac, M

    2014-08-01

    Cutaneous infections might occur in up to 80% of organ transplant recipients (OTR) and viral infections are the most common them. The risk of different skin infection is among related to the intensity of immunosuppression. During the first post-transplant period, herpes viruses are most common. After some months following transplantation, human papilloma viruses represent the most significant infections among OTR. Reactivation of herpes simplex virus in OTR can become more invasive, takes longer to heal, and shows greater potential for dissemination to visceral organs compared to the general population. Specific immunosuppressive drugs (namely muromonab and mycophenolate mofetil) have been associated with an increased risk of herpes virus reactivation after transplantation. On the other hand, there is evidence that the mTOR inhibitors, such as everolimus, may be associated with a decreased incidence of herpesvirus infections in transplant recipients. The incidence of herpes zoster in OTR is 10 to 100 fold higher than the general population, ranging from 1% to 12%. The chronic immunosuppression performed in OTR may lead to persistent replication of herpesviruses, dissemination of the virus with multivisceral involvement (hepatitis, pneumonitis, myocarditis, encephalitis and disseminated intravascular coagulation) and eventually, the emergence of antiviral-drug resistance. Viral warts are the most common cutaneous infection occurring in OTR. The number of warts increases with the duration of immunosuppressive therapy. Since warts in organ recipients are frequently multiple and only rarely undergo spontaneous regression, the therapeutic management of warts in patients treated with immunosuppressive drugs might be challenging. Imiquimod, 1% cidofovir ointment, acitretin proved to be useful off-label strategies for recalcitrant cutaneous viral warts in OTR. Extensive and atypical presentation of molluscum contagiosum has been also reported in OTR, with a prevalence

  5. Spatiotemporal modelling of viral infection dynamics

    NASA Astrophysics Data System (ADS)

    Beauchemin, Catherine

    Viral kinetics have been studied extensively in the past through the use of ordinary differential equations describing the time evolution of the diseased state in a spatially well-mixed medium. However, emerging spatial structures such as localized populations of dead cells might affect the spread of infection, similar to the manner in which a counter-fire can stop a forest fire from spreading. In the first phase of the project, a simple two-dimensional cellular automaton model of viral infections was developed. It was validated against clinical immunological data for uncomplicated influenza A infections and shown to be accurate enough to adequately model them. In the second phase of the project, the simple two-dimensional cellular automaton model was used to investigate the effects of relaxing the well-mixed assumption on viral infection dynamics. It was shown that grouping the initially infected cells into patches rather than distributing them uniformly on the grid reduced the infection rate as only cells on the perimeter of the patch have healthy neighbours to infect. Use of a local epithelial cell regeneration rule where dead cells are replaced by healthy cells when an immediate neighbour divides was found to result in more extensive damage of the epithelium and yielded a better fit to experimental influenza A infection data than a global regeneration rule based on division rate of healthy cell. Finally, the addition of immune cell at the site of infection was found to be a better strategy at low infection levels, while addition at random locations on the grid was the better strategy at high infection level. In the last project, the movement of T cells within lymph nodes in the absence of antigen, was investigated. Based on individual T cell track data captured by two-photon microscopy experiments in vivo, a simple model was proposed for the motion of T cells. This is the first step towards the implementation of a more realistic spatiotemporal model of HIV than

  6. Cytoplasmic RNA Granules and Viral Infection

    PubMed Central

    Tsai, Wei-Chih; Lloyd, Richard E.

    2016-01-01

    RNA granules are dynamic cellular structures essential for proper gene expression and homeostasis. The two principle types of cytoplasmic RNA granules are stress granules (SGs), which contain stalled translation initiation complexes, and processing bodies (P-bodies, PBs), which concentrate factors involved in mRNA degradation. RNA granules are associated with gene silencing of transcripts, thus, viruses repress RNA granule functions to favor replication. This review discusses the breadth of viral interactions with cytoplasmic RNA granules, focusing on mechanisms that modulate the functions of RNA granules and that typically promote viral replication. Currently mechanisms for virus manipulation of RNA granules can be loosely grouped into three non-exclusive categories; i) cleavage of key RNA granule factors, ii) regulation of PKR activation and iii) co-opting RNA granule factors for new roles in viral replication. Viral repression of RNA granules supports productive infection by inhibiting their gene silencing functions and counteracting their role in linking stress sensing with innate immune activation. PMID:26958719

  7. Viral infections associated with haemophagocytic syndrome.

    PubMed

    Maakaroun, Nadine Rouphael; Moanna, Abeer; Jacob, Jesse T; Albrecht, Helmut

    2010-03-01

    Haemophagocytic syndrome (HPS) or haemophagocytic lymphohistiocytosis (HLH) is a rare disease caused by a dysfunction of cytotoxic T cells and NK cells. This T cell/NK cell dysregulation causes an aberrant cytokine release, resulting in proliferation/activation of histiocytes with subsequent haemophagocytosis. Histiocytic infiltration of the reticuloendothelial system results in hepatomegaly, splenomegaly, lymphadenopathy and pancytopenia ultimately leading to multiple organ dysfunctions. Common clinical features include high fevers despite broad spectrum antimicrobials, maculopapular rash, neurological symptoms, coagulopathy and abnormal liver function tests. Haemophagocytic syndrome can be either primary, i.e. due to an underlying genetic defect or secondary, associated with malignancies, autoimmune diseases (also called macrophage activation syndrome) or infections. Infectious triggers are most commonly due to viral infections mainly of the herpes group, with EBV being the most common cause. HPS can be fatal if untreated. Early recognition of the clinical presentation and laboratory abnormalities associated with HPS and prompt initiation of treatment can be life saving. HPS triggered by viral infections generally does not respond to specific antiviral therapy but may be treated with immunosuppressive/immunomodulatory agents and, in refractory cases, with bone marrow transplantation.

  8. Phylodynamic analysis of a viral infection network

    PubMed Central

    Shiino, Teiichiro

    2012-01-01

    Viral infections by sexual and droplet transmission routes typically spread through a complex host-to-host contact network. Clarifying the transmission network and epidemiological parameters affecting the variations and dynamics of a specific pathogen is a major issue in the control of infectious diseases. However, conventional methods such as interview and/or classical phylogenetic analysis of viral gene sequences have inherent limitations and often fail to detect infectious clusters and transmission connections. Recent improvements in computational environments now permit the analysis of large datasets. In addition, novel analytical methods have been developed that serve to infer the evolutionary dynamics of virus genetic diversity using sample date information and sequence data. This type of framework, termed “phylodynamics,” helps connect some of the missing links on viral transmission networks, which are often hard to detect by conventional methods of epidemiology. With sufficient number of sequences available, one can use this new inference method to estimate theoretical epidemiological parameters such as temporal distributions of the primary infection, fluctuation of the pathogen population size, basic reproductive number, and the mean time span of disease infectiousness. Transmission networks estimated by this framework often have the properties of a scale-free network, which are characteristic of infectious and social communication processes. Network analysis based on phylodynamics has alluded to various suggestions concerning the infection dynamics associated with a given community and/or risk behavior. In this review, I will summarize the current methods available for identifying the transmission network using phylogeny, and present an argument on the possibilities of applying the scale-free properties to these existing frameworks. PMID:22993510

  9. Phosphorylation events during viral infections provide potential therapeutic targets

    PubMed Central

    Keating, Julie A.; Striker, Rob

    2012-01-01

    SUMMARY For many medically relevant viruses, there is now considerable evidence that both viral and cellular kinases play important roles in viral infection. Ultimately, these kinases, and the cellular signaling pathways that they exploit, may serve as therapeutic targets for treating patients. Currently, small molecule inhibitors of kinases are under investigation as therapy for herpes viral infections. Additionally, a number of cellular or host-directed tyrosine kinase inhibitors that have been previously FDA-approved for cancer treatment are under study in animal models and clinical trials, as they have shown promise for the treatment of various viral infections as well. This review will highlight the wide range of viral proteins phosphorylated by viral and cellular kinases, and the potential for variability of kinase recognition sites within viral substrates to impact phosphorylation and kinase prediction. Research studying kinase-targeting prophylactic and therapeutic treatments for a number of viral infections will also be discussed. PMID:22113983

  10. Recurrent and Sustained Viral Infections in Primary Immunodeficiencies

    PubMed Central

    Ruffner, Melanie A.; Sullivan, Kathleen E.; Henrickson, Sarah E.

    2017-01-01

    Viral infections are commonplace and often innocuous. Nevertheless, within the population of patients with primary immunodeficiencies (PIDDs), viral infections can be the feature that drives a diagnostic evaluation or can be the most significant morbidity for the patient. This review is focused on the viral complications of PIDDs. It will focus on respiratory viruses, the most common type of viral infection in the general population. Children and adults with an increased frequency or severity of respiratory viral infections are often referred for an immunologic evaluation. The classic teaching is to investigate humoral function in people with recurrent sinopulmonary infections, but this is often interpreted to mean recurrent bacterial infections. Recurrent or very severe viral infections may also be a harbinger of a primary immunodeficiency as well. This review will also cover persistent cutaneous viral infections, systemic infections, central nervous system infections, and gastrointestinal infections. In each case, the specific viral infections may drive a diagnostic evaluation that is specific for that type of virus. This review also discusses the management of these infections, which can become problematic in patients with PIDDs. PMID:28674531

  11. Viral coinfection in childhood respiratory tract infections.

    PubMed

    Martínez-Roig, A; Salvadó, M; Caballero-Rabasco, M A; Sánchez-Buenavida, A; López-Segura, N; Bonet-Alcaina, M

    2015-01-01

    The introduction of molecular techniques has enabled better understanding of the etiology of respiratory tract infections in children. The objective of the study was to analyze viral coinfection and its relationship to clinical severity. Hospitalized pediatric patients with a clinical diagnosis of respiratory infection were studied during the period between 2009-2010. Clinical and epidemiological data, duration of hospitalization, need for oxygen therapy, bacterial coinfection and need for mechanical ventilation were collected. Etiology was studied by multiplex PCR and low-density microarrays for 19 viruses. A total of 385 patients were positive, 44.94% under 12 months. The most frequently detected viruses were RSV-B: 139, rhinovirus: 114, RSV-A: 111, influenza A H1N1-2009: 93 and bocavirus: 77. Coinfection was detected in 61.81%, 36.36% with 2 viruses, 16.10% and 9.35% with 3 to 4 or more. Coinfection was higher in 2009 with 69.79 vs. 53.88% in 2010. Rhinovirus/RSV-B on 10 times and RSV-A/RSV-B on 5 times were the most detected coinfections. Hospitalization decreased with greater number of viruses (P<0,001). Oxygen therapy was required by 26.75% (one virus was detected in 55.34% of cases). A larger number of viruses resulted in less need for oxygen (P<0,001). Ten cases required mechanical ventilation, 4 patients with bacterial coinfection and 5 with viral coinfection (P=0,69). An inverse relationship was found between the number of viruses detected in nasopharyngeal aspirate, the need for oxygen therapy and hospitalization days. More epidemiological studies and improved quantitative detection techniques are needed to define the role of viral coinfections in respiratory disease and its correlation with the clinical severity. Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.

  12. Suppression of viral infectivity through lethal defection

    PubMed Central

    Grande-Pérez, Ana; Lázaro, Ester; Lowenstein, Pedro; Domingo, Esteban; Manrubia, Susanna C.

    2005-01-01

    RNA viruses replicate with a very high error rate and give rise to heterogeneous, highly plastic populations able to adapt very rapidly to changing environments. Viral diseases are thus difficult to control because of the appearance of drug-resistant mutants, and it becomes essential to seek mechanisms able to force the extinction of the quasispecies before adaptation emerges. An alternative to the use of conventional drugs consists in increasing the replication error rate through the use of mutagens. Here, we report about persistent infections of lymphocytic choriomeningitis virus treated with fluorouracil, where a progressive debilitation of infectivity leading to eventual extinction occurs. The transition to extinction is accompanied by the production of large amounts of RNA, indicating that the replicative ability of the quasispecies is not strongly impaired by the mutagen. By means of experimental and theoretical approaches, we propose that a fraction of the RNA molecules synthesized can behave as a defective subpopulation able to drive the viable class extinct. Our results lead to the identification of two extinction pathways, one at high amounts of mutagen, where the quasispecies completely loses its ability to infect and replicate, and a second one, at lower amounts of mutagen, where replication continues while the infective class gets extinct because of the action of defectors. The results bear on a potential application of increased mutagenesis as an antiviral strategy in that low doses of a mutagenic agent may suffice to drive persistent virus to extinction. PMID:15767582

  13. Laboratory techniques for rapid diagnosis of viral infections: a Memorandum*

    PubMed Central

    1977-01-01

    This Memorandum evaluates rapid laboratory techniques for the diagnosis of viral infections, especially with a view to their use in developing countries. These techniques comprise the detection of viral antigens by immunofluorescence and immunoperoxidase techniques and methods of viral antibody and antigen determination by the enzyme immunoassay technique. A number of general and specific recommendations are made. PMID:330016

  14. Glycosylation, Hypogammaglobulinemia, and Resistance to Viral Infections

    PubMed Central

    Chun, Tae-Wook; Lusso, Paolo; Kaplan, Gerardo; Wolfe, Lynne; Memoli, Matthew J.; He, Miao; Vega, Hugo; Kim, Leo J.Y.; Huang, Yan; Hussein, Nadia; Nievas, Elma; Mitchell, Raquel; Garofalo, Mary; Louie, Aaron; Ireland, Derek C.; Grunes, Claire; Cimbro, Raffaello; Patel, Vyomesh; Holzapfel, Genevieve; Salahuddin, Daniel; Bristol, Tyler; Adams, David; Marciano, Beatriz E.; Hegde, Madhuri; Li, Yuxing; Calvo, Katherine R.; Stoddard, Jennifer; Justement, J. Shawn; Jacques, Jerome; Priel, Debra A. Long; Murray, Danielle; Sun, Peter; Kuhns, Douglas B.; Boerkoel, Cornelius F.; Chiorini, John A.; Di Pasquale, Giovanni; Verthelyi, Daniela; Rosenzweig, Sergio D.

    2014-01-01

    Summary Genetic defects in MOGS, the gene encoding mannosyl-oligosaccharide glucosidase (the first enzyme in the processing pathway of N-linked oligosaccharide), cause the rare congenital disorder of glycosylation type IIb (CDG-IIb), also known as MOGS-CDG. MOGS is expressed in the endoplasmic reticulum and is involved in the trimming of N-glycans. We evaluated two siblings with CDG-IIb who presented with multiple neurologic complications and a paradoxical immunologic phenotype characterized by severe hypogammaglobulinemia but limited clinical evidence of an infectious diathesis. A shortened immunoglobulin half-life was determined to be the mechanism underlying the hypogammaglobulinemia. Impaired viral replication and cellular entry may explain a decreased susceptibility to infections. PMID:24716661

  15. Subversion of the actin cytoskeleton during viral infection

    PubMed Central

    Taylor, Matthew P.; Koyuncu, Orkide O.; Enquist, Lynn W.

    2011-01-01

    Viral infection converts the normal functions of a cell to optimize viral replication and virion production. One striking observation of this conversion is the reconfiguration and reorganization of cellular actin, affecting every stage of the viral life cycle, from entry through assembly to egress. The extent and degree of cytoskeletal reorganization varies among different viral infections, suggesting the evolution of myriad viral strategies. In this Review, we describe how the interaction of viral proteins with the cell modulates the structure and function of the actin cytoskeleton to initiate, sustain and spread infections. The molecular biology of such interactions continues to engage virologists in their quest to understand viral replication and informs cell biologists about the role of the cytoskeleton in the uninfected cell. PMID:21522191

  16. Effects of cannabinoids and their receptors on viral infections.

    PubMed

    Tahamtan, Alireza; Tavakoli-Yaraki, Masoumeh; Rygiel, Tomasz P; Mokhtari-Azad, Talat; Salimi, Vahid

    2016-01-01

    Cannabinoids, the active ingredient in marijuana, and their derivatives have received remarkable attention in the last two decades because they can affect tumor growth and metastasis. There is a large body of evidence from in vivo and in vitro models showing that cannabinoids and their receptors influence the immune system, viral pathogenesis, and viral replication. The present study reviews current insights into the role of cannabinoids and their receptors on viral infections. The results reported here indicate that cannabinoids and their receptors have different sequels for viral infection. Although activation or inhibition of cannabinoid receptors in the majority of viral infections are proper targets for development of safe and effective treatments, caution is required before using pharmaceutical cannabinoids as a treatment agent for patients with viral infections.

  17. THE INFLUENCE OF CORTISONE ON EXPERIMENTAL VIRAL INFECTION

    PubMed Central

    Kilbourne, Edwin D.

    1957-01-01

    The administration of cortisone to chicken embryos infected with influenza B virus results in (a) an initial inhibition of viral synthesis and (b) an eventual increase in the final yield of virus attained. Increased yields of virus are attained regardless of the number of viral particles in the infecting inoculum or the proportion of particles which are infective. Changes in the distribution ratios of allantoic fluid and intramembrane virus are effected by cortisone only as the secondary result of reduction in viral synthesis. The manifest effect of cortisone on influenza A virus increase is inhibitory unless inocula containing relatively high proportions of inactive viral particles are used. PMID:13481248

  18. [Viral nosocomial infections: the problem of contemporary hospital management].

    PubMed

    Hermanowska-Szpakowicz, Teresa; Zajkowska, Joanna M; Pancewicz, Sławomir A; Kondrusik, Maciej; Grygorczuk, Sambor S

    2003-01-01

    The most frequent viral pathogens which are the cause of nosocomial infections were presented. Influenza and parainfluenza viruses as well as RS virus affect frequently respiratory tract. So called enteric viruses which are rotaviruses, adenoviruses, small round viruses, astroviruses, caliciviruses, corona viruses, Coxackie, ECHO may be the agents of disorders in digestive tract in the form of intoxications. Viruses of viral hepatitis B, C, D and HIV, CMV, EBV may be the source of nosocomial viral infections transmitted by blood (transfusions).

  19. Epigenetic Treatment of Persistent Viral Infections.

    PubMed

    Moos, Walter H; Pinkert, Carl A; Irwin, Michael H; Faller, Douglas V; Kodukula, Krishna; Glavas, Ioannis P; Steliou, Kosta

    2017-02-01

    Preclinical Research Approximately 2,500 years ago, Hippocrates used the word herpes as a medical term to describe lesions that appeared to creep or crawl on the skin, advocating heat as a possible treatment. During the last 50 years, pharmaceutical research has made great strides, and therapeutic options have expanded to include small molecule antiviral agents, protease inhibitors, preventive vaccines for a handful of the papillomaviruses, and even cures for hepatitis C virus infections. However, effective treatments for persistent and recurrent viral infections, particularly the highly prevalent herpesviruses, continue to represent a significant unmet medical need, affecting the majority of the world's population. Exploring the population diversity of the human microbiome and the effects its compositional variances have on the immune system, health, and disease are the subjects of intense investigational research and study. Among the collection of viruses, bacteria, fungi, and single-cell eukaryotes that comprise the human microbiome, the virome has been grossly understudied relative to the influence it exerts on human pathophysiology, much as mitochondria have until recently failed to receive the attention they deserve, given their critical biomedical importance. Fortunately, cellular epigenetic machinery offers a wealth of druggable targets for therapeutic intervention in numerous disease indications, including those outlined above. With advances in synthetic biology, engineering our body's commensal microorganisms to seek out and destroy pathogenic species is clearly on the horizon. This is especially the case given recent breakthroughs in genetic manipulation with tools such as the CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated) gene-editing platforms. Tying these concepts together with our previous work on the microbiome and neurodegenerative and neuropsychiatric diseases, we suggest that, because mammalian cells

  20. Spontaneous Clearance of Viral Infections by Mesoscopic Fluctuations

    PubMed Central

    Chaudhury, Srabanti; Perelson, Alan S.; Sinitstyn, Nikolai A.

    2012-01-01

    Spontaneous disease extinction can occur due to a rare stochastic fluctuation. We explore this process, both numerically and theoretically, in two minimal models of stochastic viral infection dynamics. We propose a method that reduces the complexity in models of viral infections so that the remaining dynamics can be studied by previously developed techniques for analyzing epidemiological models. Using this technique, we obtain an expression for the infection clearance time as a function of kinetic parameters. We apply our theoretical results to study stochastic infection clearance for specific stages of HIV and HCV dynamics. Our results show that the typical time for stochastic clearance of a viral infection increases exponentially with the size of the population, but infection still can be cleared spontaneously within a reasonable time interval in a certain population of cells. We also show that the clearance time is exponentially sensitive to the viral decay rate and viral infectivity but only linearly dependent on the lifetime of an infected cell. This suggests that if standard drug therapy fails to clear an infection then intensifying therapy by adding a drug that reduces the rate of cell infection rather than immune modulators that hasten infected cell death may be more useful in ultimately clearing remaining pockets of infection. PMID:22693646

  1. Review of bacterial and viral zoonotic infections transmitted by dogs

    PubMed Central

    Ghasemzadeh, I; Namazi, SH

    2015-01-01

    Dogs are a major reservoir for zoonotic infections. Dogs transmit several viral and bacterial diseases to humans. Zoonotic diseases can be transmitted to human by infected saliva, aerosols, contaminated urine or feces and direct contact with the dog. Viral infections such as rabies and norovirus and bacterial infections including Pasteurella, Salmonella, Brucella, Yersinia enterocolitica, Campylobacter, Capnocytophaga, Bordetella bronchiseptica, Coxiella burnetii, Leptospira, Staphylococcus intermedius and Methicillin resistance staphylococcus aureus are the most common viral and bacterial zoonotic infections transmitted to humans by dogs. This review, focused on the mentioned infectious diseases by describing general information, signs and symptoms, transmission ways, prevention and treatment of the infection. As far as the infections are concerned, the increase of the knowledge and the awareness of dog owners and the general population regarding zoonotic infections could significantly mitigate zoonoses transmission and consequently their fatal complications. PMID:28316698

  2. Studying the immune response to human viral infections using zebrafish.

    PubMed

    Goody, Michelle F; Sullivan, Con; Kim, Carol H

    2014-09-01

    Humans and viruses have a long co-evolutionary history. Viral illnesses have and will continue to shape human history: from smallpox, to influenza, to HIV, and beyond. Animal models of human viral illnesses are needed in order to generate safe and effective antiviral medicines, adjuvant therapies, and vaccines. These animal models must support the replication of human viruses, recapitulate aspects of human viral illnesses, and respond with conserved immune signaling cascades. The zebrafish is perhaps the simplest, most commonly used laboratory model organism in which innate and/or adaptive immunity can be studied. Herein, we will discuss the current zebrafish models of human viral illnesses and the insights they have provided. We will highlight advantages of early life stage zebrafish and the importance of innate immunity in human viral illnesses. We will also discuss viral characteristics to consider before infecting zebrafish with human viruses as well as predict other human viruses that may be able to infect zebrafish.

  3. Measles virus induces persistent infection by autoregulation of viral replication

    PubMed Central

    Doi, Tomomitsu; Kwon, Hyun-Jeong; Honda, Tomoyuki; Sato, Hiroki; Yoneda, Misako; Kai, Chieko

    2016-01-01

    Natural infection with measles virus (MV) establishes lifelong immunity. Persistent infection with MV is likely involved in this phenomenon, as non-replicating protein antigens never induce such long-term immunity. Although MV establishes stable persistent infection in vitro and possibly in vivo, the mechanism by which this occurs is largely unknown. Here, we demonstrate that MV changes the infection mode from lytic to non-lytic and evades the innate immune response to establish persistent infection without viral genome mutation. We found that, in the persistent phase, the viral RNA level declined with the termination of interferon production and cell death. Our analysis of viral protein dynamics shows that during the establishment of persistent infection, the nucleoprotein level was sustained while the phosphoprotein and large protein levels declined. The ectopic expression of nucleoprotein suppressed viral replication, indicating that viral replication is self-regulated by nucleoprotein accumulation during persistent infection. The persistently infected cells were able to produce interferon in response to poly I:C stimulation, suggesting that MV does not interfere with host interferon responses in persistent infection. Our results may provide mechanistic insight into the persistent infection of this cytopathic RNA virus that induces lifelong immunity. PMID:27883010

  4. Prostaglandin E2 As a Modulator of Viral Infections

    PubMed Central

    Sander, Willem J.; O'Neill, Hester G.; Pohl, Carolina H.

    2017-01-01

    Viral infections are a major cause of infectious diseases worldwide. Inflammation and the immune system are the major host defenses against these viral infection. Prostaglandin E2 (PGE2), an eicosanoid generated by cyclooxygenases, has been shown to modulate inflammation and the immune system by regulating the expression/concentration of cytokines. The effect of PGE2 on viral infection and replication is cell type- and virus-family-dependent. The host immune system can be modulated by PGE2, with regards to immunosuppression, inhibition of nitrogen oxide (NO) production, inhibition of interferon (IFN) and apoptotic pathways, and inhibition of viral receptor expression. Furthermore, PGE2 can play a role in viral infection directly by increasing the production and release of virions, inhibiting viral binding and replication, and/or stimulating viral gene expression. PGE2 may also have a regulatory role in the induction of autoimmunity and in signaling via Toll-like receptors. In this review the known effects of PGE2 on the pathogenesis of various infections caused by herpes simplex virus, rotavirus, influenza A virus and human immunodeficiency virus as well the therapeutic potential of PGE2 are discussed. PMID:28261111

  5. Bovine viral diarrhea virus (BVDV) infections in pigs.

    PubMed

    Tao, Jie; Liao, Jinhu; Wang, Yin; Zhang, Xinjun; Wang, Jianye; Zhu, Guoqiang

    2013-08-30

    Cattle are the natural hosts of bovine viral diarrhea virus (BVDV), which causes mucosal disease, respiratory and gastrointestinal tract infections, and reproductive problems in cattle. However, BVDV can also infect goats, sheep, deer, and pigs. The prevalence of BVDV infection in pig herds has substantially increased in the last several years, causing increased economic losses to the global pig breeding industry. This article is a summary of BVDV infections in pigs, including a historical overview, clinical signs, pathology, source of infection, genetic characteristics, impacts of porcine BVDV infection for diagnosis of classical swine fever virus (CSFV), differentiation of infection with CSFV and BVDV, and future prospects of porcine BVDV infection.

  6. Immunological aspects in viral hepatitis B and C infection.

    PubMed

    Manea, Irena; Manea, Cristian Nicolae; Miron, Nicolae; Cristea, Victor

    2011-01-01

    Worldwide, viral hepatitis chronic infections are a serious health problem and a very interesting topic for both clinicians and researchers. Viral hepatitis has a variety of clinical forms: mild, inactive or severe and with a slow evolution, whose architectural structure of the hepatic tissue evolves towards cirrhosis or hepatocellular carcinoma. Sometimes, the virally induced hepatic injury evolves spectacularly and rapidly leads to exitus. The factors that generate this evolution pattern depend on the immune response of the host and equally on the viral survival and immune surveillance avoidance strategies. This paper aims to resume new discoveries in the field of immunology of the B and C viral hepatitis infection, from the perspective of the complex interactions between virus and host.

  7. Roles of LncRNAs in Viral Infections

    PubMed Central

    Liu, Weiwei; Ding, Chan

    2017-01-01

    Many proteins and signaling pathways participate in anti-viral host responses. Long non-coding RNAs (lncRNAs), a subset of non-coding RNAs greater than 200 nucleotides in length, have been recently described as critical regulators in viral infections. Accumulating research indicates that lncRNAs are important in the development and progression of infectious diseases. LncRNAs are not only involved in anti-viral responses, but in many different virus-host interactions, some of which may be beneficial to the virus. Here we review the current knowledge regarding host and viral lncRNAs and their roles in viral infections. In addition, the potential of using lncRNAs as diagnostic biomarkers is discussed. PMID:28603696

  8. Exploring viral infection using single-cell sequencing.

    PubMed

    Rato, Sylvie; Golumbeanu, Monica; Telenti, Amalio; Ciuffi, Angela

    2016-11-02

    Single-cell sequencing (SCS) has emerged as a valuable tool to study cellular heterogeneity in diverse fields, including virology. By studying the viral and cellular genome and/or transcriptome, the dynamics of viral infection can be investigated at single cell level. Most studies have explored the impact of cell-to-cell variation on the viral life cycle from the point of view of the virus, by analyzing viral sequences, and from the point of view of the cell, mainly by analyzing the cellular host transcriptome. In this review, we will focus on recent studies that use single-cell sequencing to explore viral diversity and cell variability in response to viral replication.

  9. THE INFLUENCE OF CORTISONE ON EXPERIMENTAL VIRAL INFECTION

    PubMed Central

    Kilbourne, Edwin D.

    1957-01-01

    Cortisone is a highly potent inhibitor of influenza virus synthesis in the chick embryo, inducing manifest inhibition in doses of 0.1 to 1.0 µg/egg. Inhibition of viral synthesis is only temporarily manifest. As infection continues, the negation by cortisone of the self-limiting effects of viral autointerference obscures the coincident cortisone effect on synthesis. The inhibitory effect of cortisone may be induced late in the course of viral multiplication, after conclusion of the latent period. It is proposed that inhibition of viral synthesis with cortisone is a corollary of the steroid's inhibitory effects on growth and protein synthesis of the infected host. The role of adrenal corticoids in the regulation of infection with obligate intracellular parasites deserves continued investigation. PMID:13481250

  10. 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

  11. The contribution of viral genotype to plasma viral set-point in HIV infection.

    PubMed

    Hodcroft, Emma; Hadfield, Jarrod D; Fearnhill, Esther; Phillips, Andrew; Dunn, David; O'Shea, Siobhan; Pillay, Deenan; Leigh Brown, Andrew J

    2014-05-01

    Disease progression in HIV-infected individuals varies greatly, and while the environmental and host factors influencing this variation have been widely investigated, the viral contribution to variation in set-point viral load, a predictor of disease progression, is less clear. Previous studies, using transmission-pairs and analysis of phylogenetic signal in small numbers of individuals, have produced a wide range of viral genetic effect estimates. Here we present a novel application of a population-scale method based in quantitative genetics to estimate the viral genetic effect on set-point viral load in the UK subtype B HIV-1 epidemic, based on a very large data set. Analyzing the initial viral load and associated pol sequence, both taken before anti-retroviral therapy, of 8,483 patients, we estimate the proportion of variance in viral load explained by viral genetic effects to be 5.7% (CI 2.8-8.6%). We also estimated the change in viral load over time due to selection on the virus and environmental effects to be a decline of 0.05 log10 copies/mL/year, in contrast to recent studies which suggested a reported small increase in viral load over the last 20 years might be due to evolutionary changes in the virus. Our results suggest that in the UK epidemic, subtype B has a small but significant viral genetic effect on viral load. By allowing the analysis of large sample sizes, we expect our approach to be applicable to the estimation of the genetic contribution to traits in many organisms.

  12. Association of Bovine Viral Diarrhea Virus with Multiple Viral Infections in Bovine Respiratory Disease Outbreaks

    PubMed Central

    Richer, Lisette; Marois, Paul; Lamontagne, Lucie

    1988-01-01

    We investigated eleven outbreaks of naturally occurring bovine respiratory diseases in calves and adult animals in the St-Hyacinthe area of Quebec. Specific antibodies to bovine herpesvirus-1, bovine viral diarrhea virus, respiratory syncytial virus, parainfluenza type 3 virus, reovirus type 3, and serotypes 1 to 7 of bovine adenovirus were found in paired sera from diseased animals. Several bovine viruses with respiratory tropism were involved concomitantly in herds during an outbreak of bovine respiratory disease. In addition, concomitant fourfold rises of antibody titers were frequently observed to two or more viral agents in seroconverted calves (61%) or adult animals (38%). Bovine viral diarrhea virus was found to be the most frequent viral agent associated with multiple viral infection in calves only (92%). PMID:17423116

  13. Emerging infectious diseases with cutaneous manifestations: Viral and bacterial infections.

    PubMed

    Nawas, Zeena Y; Tong, Yun; Kollipara, Ramya; Peranteau, Andrew J; Woc-Colburn, Laila; Yan, Albert C; Lupi, Omar; Tyring, Stephen K

    2016-07-01

    Given increased international travel, immigration, and climate change, bacterial and viral infections that were once unrecognized or uncommon are being seen more frequently in the Western Hemisphere. A delay in diagnosis and treatment of these diseases can lead to significant patient morbidity and mortality. However, the diagnosis and management of these infections is fraught with a lack of consistency because there is a dearth of dermatology literature on the cutaneous manifestations of these infections. We review the epidemiology, cutaneous manifestations, diagnosis, and management of these emerging bacterial and viral diseases.

  14. Effect of DNA Repair Protein Rad18 on Viral Infection

    PubMed Central

    Lloyd, Aliza G; Tateishi, Satoshi; Bieniasz, Paul D; Muesing, Mark A; Yamaizumi, Masaru; Mulder, Lubbertus C. F

    2006-01-01

    Host factors belonging to the DNA repair machineries are assumed to aid retroviruses in the obligatory step of integration. Here we describe the effect of DNA repair molecule Rad18, a component of the post-replication repair pathway, on viral infection. Contrary to our expectations, cells lacking Rad18 were consistently more permissive to viral transduction as compared to Rad18+/+ controls. Remarkably, such susceptibility was integration independent, since retroviruses devoid of integration activity also showed enhancement of the initial steps of infection. Moreover, the elevated sensitivity of the Rad18−/− cells was also observed with adenovirus. These data indicate that Rad18 suppresses viral infection in a non-specific fashion, probably by targeting incoming DNA. Furthermore, considering data published recently, it appears that the interactions between DNA repair components with incoming viruses, often result in inhibition of the infection rather than cooperation toward its establishment. PMID:16710452

  15. Redox Imbalance and Viral Infections in Neurodegenerative Diseases

    PubMed Central

    Limongi, Dolores

    2016-01-01

    Reactive oxygen species (ROS) are essential molecules for many physiological functions and act as second messengers in a large variety of tissues. An imbalance in the production and elimination of ROS is associated with human diseases including neurodegenerative disorders. In the last years the notion that neurodegenerative diseases are accompanied by chronic viral infections, which may result in an increase of neurodegenerative diseases progression, emerged. It is known in literature that enhanced viral infection risk, observed during neurodegeneration, is partly due to the increase of ROS accumulation in brain cells. However, the molecular mechanisms of viral infection, occurring during the progression of neurodegeneration, remain unclear. In this review, we discuss the recent knowledge regarding the role of influenza, herpes simplex virus type-1, and retroviruses infection in ROS/RNS-mediated Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS). PMID:27110325

  16. Issues and updates in emerging neurologic viral infections.

    PubMed

    Wilson, Michael R; Tyler, Kenneth L

    2011-07-01

    This review discusses the recent advances in the identification of viral pathogens and other etiologies responsible for cases of suspected viral encephalitis. The authors describe new molecular diagnostic strategies for identifying novel causes of viral encephalitis, including MassTag PCR, DNA microarrays, and high-throughput DNA pyrosequencing. They also highlight the increasing recognition of immune-mediated causes of encephalitis among those cases previously thought to be viral encephalitis of unknown etiology. Lastly, they review some of the most recent updates in the field of emerging neurologic viral infections impacting the United States, including the neurologic complications of H1N1 virus and the reemergence of dengue virus in the Florida Keys.

  17. Basic stochastic models for viral infection within a host.

    PubMed

    Vidurupola, Sukhitha W; Allen, Linda J S

    2012-10-01

    Stochastic differential equation (SDE) models are formulated for intra-host virus-cell dynamics during the early stages of viral infection, prior to activation of the immune system. The SDE models incorporate more realism into the mechanisms for viral entry and release than ordinary differential equation (ODE) models and show distinct differences from the ODE models. The variability in the SDE models depends on the concentration, with much greater variability for small concentrations than large concentrations. In addition, the SDE models show significant variability in the timing of the viral peak. The viral peak is earlier for viruses that are released from infected cells via bursting rather than via budding from the cell membrane.

  18. The global burden of bacterial and viral zoonotic infections.

    PubMed

    Christou, L

    2011-03-01

    Bacterial and viral zoonotic infections comprise a practically endless, ever-expanding list of pathogens that have the potential to induce human disease of varying severity, with varying means of transmission to humans (including vector-borne and foodborne agents) and of varying epidemiology. Not all theoretically zoonotic pathogens are truly zoonotic in practice, the prime example being influenza viruses; aviann H5N1 influenza remains strictly zoonotic, whereas novel H1N1 influenza displays an anthropocentric cycle that led to a pandemic, despite being of zoonotic origin. The burden of disease induced by zoonotic and viral pathogens is enormous: there are more than ten bacterial zoonoses, each of which affects hundreds of thousands patients annually, often leading to chronic infections and causing significant economic losses of a medical and livestock-related nature. Viral zoonotic agents are constantly emerging or re-emerging, and are associated with outbreaks of limited or expanded geographical spread: the typical trends of viral zoonotic infections, however, is to extend their ecological horizon, sometimes in an unexpected but successful manner, as in the case of West Nile virus, and in other instances less effectively, as was the case, fortunately, in the case of avian influenza. The majority of bacterial and viral zoonotic infections attract disproportionately low scientific and public health interest. Understanding their burden may allow for improved surveillance and prevention measures. © 2011 The Author. Clinical Microbiology and Infection © 2011 European Society of Clinical Microbiology and Infectious Diseases.

  19. Benign Testis Mass After Viral Infection.

    PubMed

    Hurtt, Robbie; Pound, Charles; Bean, Christopher

    2017-05-01

    We present two cases of viral associated orchitis and subsequent testis masses concerning for malignancy both on physical exam and scrotal ultrasound. In both cases, the patients underwent radical orchiectomy after a discussion of management options. Both pathologic analyses were negative for malignancy, and our literature search revealed no other similar case reports. We review our two cases specifically, as well as briefly review orchitis and discuss possible management strategies of similar cases.

  20. Nasopharyngeal polymicrobial colonization during health, viral upper respiratory infection and upper respiratory bacterial infection.

    PubMed

    Xu, Qingfu; Wischmeyer, Jareth; Gonzalez, Eduardo; Pichichero, Michael E

    2017-07-01

    We sought to understand how polymicrobial colonization varies during health, viral upper respiratory infection (URI) and acute upper respiratory bacterial infection to understand differences in infection-prone vs. non-prone patients. Nasopharyngeal (NP) samples were collected from 74 acute otitis media (AOM) infection-prone and 754 non-prone children during 2094 healthy visits, 673 viral URI visits and 631 AOM visits. Three otopathogens Streptococcus pneumoniae (Spn), Nontypeable Haemophilus influenzae (NTHi), and Moraxella catarrhalis (Mcat) were identified by culture. NP colonization rates of multiple otopathogens during health were significantly lower than during viral URI, and during URI they were lower than at onset of upper respiratory bacterial infection in both AOM infection-prone and non-prone children. AOM infection-prone children had higher polymicrobial colonization rates than non-prone children during health, viral URI and AOM. Polymicrobial colonization rates of AOM infection-prone children during health were equivalent to that of non-prone children during viral URI, and during viral URI were equivalent to that of non-prone during AOM infection. Spn colonization was positively associated with NTHi and Mcat colonization during health, but negatively during AOM infection. The infection-prone patients more frequently have multiple potential bacterial pathogens in the NP than the non-prone patients. Polymicrobial interaction in the NP differs during health and at onset of infection. Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  1. Systemic viral infections and their retinal and choroidal manifestations.

    PubMed

    Yoser, S L; Forster, D J; Rao, N A

    1993-01-01

    Viruses are one of the most common causes of infections involving the posterior segment of the eye. Such infections can occur either on a congenital or an acquired basis, and may affect primarily the retina or the choroid. Congenital cytomegalovirus (CMV) and rubella infections may result in retinitis. CMV retinitis is also the most common cause of acquired viral retinitis, primarily because of the acquired immunodeficiency syndrome (AIDS). Other types of viral retinitis, such as those caused by herpes simplex or herpes zoster, can occur in immunocompromised or immunocompetent individuals. Retinitis or choroiditis caused by viruses such as measles, influenza, Epstein-Barr virus, and Rift Valley fever virus, typically occurs subsequent to an acute viral systemic illness. The systemic and ocular manifestations, as well as the histopathology, laboratory tests, differential diagnoses, and treatment regimens for each of the individual viruses are discussed in detail.

  2. Viral infection as a regulator of oceanic phytoplankton populations

    NASA Astrophysics Data System (ADS)

    Rhodes, C. J.; Truscott, J. E.; Martin, A. P.

    2008-11-01

    Viruses are the most abundant organism in seawater across all the world's oceans. Though they are believed to be capable of infecting all phytoplankton species their role in regulating plankton population levels is not well understood. In order to gain an understanding of the potential influence of viruses on phytoplankton population dynamics, particularly 'blooms', two plankton ecosystem models with explicit representation of viruses and virally infected phytoplankton are presented, and an initial investigation into their range of behaviours explored. The models are extensions of well-established plankton ecosystem models that now permit the possibility of viral infection and mortality of phytoplankton. Ecological and epidemiological parameters from a number of sources are used to furnish the models. The models are shown to be capable of capturing known features of phytoplankton population dynamics in the presence of viruses: viruses can stably co-exist in the plankton ecosystem without the need to invoke other stabilising processes, and infection can serve to suppress primary production and phytoplankton abundance whilst boosting nutrient levels. Intuitively, viral infection will be most effective when phytoplankton is high. We therefore use the two models to investigate the influence of viral infection on 'blooms' in two independent ways: first with a seasonally-forced variability and second with a triggered transient event. It is demonstrated that the impact of viruses can be very noticeable during episodes of enhanced phytoplankton density found during 'blooms'. Viruses serve to attenuate the intensity and duration of these transient events in a manner consistent with observations.

  3. Antioxidants in patients with dengue viral infection.

    PubMed

    Chandrasena, Lal G; Peiris, Hemantha; Kamani, J; Wanigasuriya, P; Jayaratne, Shantilal D; Wijayasiri, W A A; Wijesekara, G Udaya S

    2014-09-01

    An alteration in the oxidation/reduction (redox) status of humans infected with virus infections may contrioute to tefl pariiogeiiesin anu ciniiua1 manifestations of the disease. Alterations in redox markers begin prior to the onset of clinical symptoms, suggesting early changes in the oxidant/antioxidant balance. Early identification of redox markers may be of clinical usefulness in the management of patients with dengue virus infection. We conducted a hospital based comparative cross sectional study of 55 patients serologically confirmed to have dengue infection and 55 clinically healthy age and sex matched subjects as controls to assess oxidative stress in acute dengue virus infection. Blood samples were drawn on the fifth day after symptom onset and analyzed for Trolox equivalent antioxidant capacity (TEAC), reduced glutathione (GSH), glutathione peroxidase (GPx) and paraoxonase (PON) activity. The results showed significantly lower levels of plasma TEAC, serum PON and erythrocyte GSH and GPx activity among dengue patients than in controls. Of the antioxidants investigated, PON appeared to be the most sensitive marker of oxidative stress in dengue virus infection. Serum PON may be a potentially useful marker of oxidative stress in patients with dengue virus infection.

  4. Viral infections in travellers from tropical Africa.

    PubMed

    Woodruff, A W; Bowen, E T; Platt, G S

    1978-04-15

    Examination of sera from 86 travellers to Britain from tropical Africa disclosed evidence of past infection with 10 identifiable viruses, of which the most important were O'nyong-nyong, dengue, chikungunya, and Ntaya. The findings indicate that infection with O'nyong-nyong may be acquired sporadically in Nigeria, Ghana, and Sierra Leone, where it has not previously been identified. Chikungunya infection had not been recorded in West Africa other than Nigeria and Senegal. Patients from Sierra Leone and contiguous Liberia had antibodies to this infection. An outbread of dengue fever in the Seychelles in early 1977 was confirmed. Ntaya virus, though known in Uganda, Cameroon, and Zaire, appears also to be transmitted in Kenya, Nigeria, and Zambia. Clinical studies indicated that chikungunya infection may present with alimentary features, possibly with jaundice. The clinical features of Ntaya infection may include kizarre neurological manifestations in addition to fever. The absence of Lassa antibodies among these travellers suggested that this infection is not a common hazard among such persons.

  5. Viral infections as controlling factors for the deep biosphere? (Invited)

    NASA Astrophysics Data System (ADS)

    Engelen, B.; Engelhardt, T.; Sahlberg, M.; Cypionka, H.

    2009-12-01

    The marine deep biosphere represents the largest biotope on Earth. Throughout the last years, we have obtained interesting insights into its microbial community composition. However, one component that was completely overlooked so far is the viral inventory of deep-subsurface sediments. While viral infections were identified to have a major impact on the benthic microflora of deep-sea surface sediments (Danavaro et al. 2008), no studies were performed on deep-biosphere samples, so far. As grazers probably play only a minor role in anoxic and highly compressed deep sediments, viruses might be the main “predators” for indigenous microorganisms. Furthermore, the release of cell components, called “the viral shunt”, could have a major impact on the deep biosphere in providing labile organic compounds to non-infected microorganisms in these generally nutrient depleted sediments. However, direct counting of viruses in sediments is highly challenging due to the small size of viruses and the high background of small particles. Even molecular surveys using “universal” PCR primers that target phage-specific genes fail due to the vast phage diversity. One solution for this problem is the lysogenic viral life cycle as many bacteriophages integrate their DNA into the host genome. It is estimated that up to 70% of cultivated bacteria contain prophages within their genome. Therefore, culture collections (Batzke et al. 2007) represent an archive of the viral composition within the respective habitat. These prophages can be induced to become free phage particles in stimulation experiments in which the host cells are set under certain stress situations such as a treatment with UV exposure or DNA-damaging antibiotics. The study of the viral component within the deep biosphere offers to answer the following questions: To which extent are deep-biosphere populations controlled by viral infections? What is the inter- and intra-specific diversity and the host-specific viral

  6. Protective Effect of Ginseng Polysaccharides on Influenza Viral Infection

    PubMed Central

    Yoo, Dae-Goon; Kim, Min-Chul; Park, Min-Kyung; Park, Kyoung-Mi; Quan, Fu-Shi; Song, Jae-Min; Wee, Jae Joon; Wang, Bao-Zhong; Cho, Young-Keol; Compans, Richard W.; Kang, Sang-Moo

    2012-01-01

    Ginseng polysaccharide has been known to have multiple immunomodulatory effects. In this study, we investigated whether Panax ginseng polysaccharide (GP) would have a preventive effect on influenza infection. Administration of mice with GP prior to infection was found to confer a survival benefit against infection with H1N1 (A/PR/8/34) and H3N2 (A/Philippines/82) influenza viruses. Mice infected with the 2009 H1N1 virus suspended in GP solution showed moderately enhanced survival rates and lower levels of lung viral titers and the inflammatory cytokine (IL-6). Daily treatment of vaccinated mice with GP improved their survival against heterosubtypic lethal challenge. This study demonstrates the first evidence that GP can be used as a remedy against influenza viral infection. PMID:22442708

  7. Viral immunity. Transkingdom control of viral infection and immunity in the mammalian intestine.

    PubMed

    Pfeiffer, Julie K; Virgin, Herbert W

    2016-01-15

    Viruses that infect the intestine include major human pathogens (retroviruses, noroviruses, rotaviruses, astroviruses, picornaviruses, adenoviruses, herpesviruses) that constitute a serious public health problem worldwide. These viral pathogens are members of a large, complex viral community inhabiting the intestine termed "the enteric virome." Enteric viruses have intimate functional and genetic relationships with both the host and other microbial constituents that inhabit the intestine, such as the bacterial microbiota, their associated phages, helminthes, and fungi, which together constitute the microbiome. Emerging data indicate that enteric viruses regulate, and are in turn regulated by, these other microbes through a series of processes termed "transkingdom interactions." This represents a changing paradigm in intestinal immunity to viral infection. Here we review recent advances in the field and propose new ways in which to conceptualize this important area.

  8. [Lacrimal and salivary antioxidants in viral infection].

    PubMed

    Terekhina, N A; Petrovich, Iu A; Batueva, R A; Sosnin, D Iu; Vesna, V A

    1998-01-01

    The activities of antioxidant enzymes in the cornea and tears in patients with ophthalmic herpes and in the saliva in those with herpetic stomatitis were assessed. Impaired inhibition of hydroxy radical and a drop of antioxidant enzymes activities and of the level of ascorbic acid in herpes-infected cornea and tears are factors in the pathogenesis of ophthalmic herpes. Measurements of enzymatic activities in the tears and saliva in herpetic infection are a valuable diagnostic test and a criterion of treatment efficacy.

  9. Viral infections in allergy and immunology: How allergic inflammation influences viral infections and illness.

    PubMed

    Edwards, Michael R; Strong, Katherine; Cameron, Aoife; Walton, Ross P; Jackson, David J; Johnston, Sebastian L

    2017-10-01

    Viral respiratory tract infections are associated with asthma inception in early life and asthma exacerbations in older children and adults. Although how viruses influence asthma inception is poorly understood, much research has focused on the host response to respiratory viruses and how viruses can promote; or how the host response is affected by subsequent allergen sensitization and exposure. This review focuses on the innate interferon-mediated host response to respiratory viruses and discusses and summarizes the available evidence that this response is impaired or suboptimal. In addition, the ability of respiratory viruses to act in a synergistic or additive manner with TH2 pathways will be discussed. In this review we argue that these 2 outcomes are likely linked and discuss the available evidence that shows reciprocal negative regulation between innate interferons and TH2 mediators. With the renewed interest in anti-TH2 biologics, we propose a rationale for why they are particularly successful in controlling asthma exacerbations and suggest ways in which future clinical studies could be used to find direct evidence for this hypothesis. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  10. Tumor necrosis factor blockade and the risk of viral infection

    PubMed Central

    Kim, Seo Young; Solomon, Daniel H.

    2011-01-01

    Tumor necrosis factor (TNF)-α blockers have been widely used to treat rheumatoid arthritis and other inflammatory diseases. An increased risk of tuberculosis and opportunistic infections with TNF-α blockers has been well reported because of the primary role of TNF-α in host defense and immune response. However, little is known about the association between TNF-α blockers and viral infections. Because interferon-γ and TNF-α play critical roles in the control of viral infection, depletion of TNF by treatment with TNF-α blockade may facilitate the risk of or reactivation of viral infection. Several large observational studies have recently found an increased risk of herpes zoster in patients receiving TNF-α blockers for rheumatoid arthritis. This review draws attention to several important viral infections such as human immunodeficiency, varicella-zoster and Epstein-Barr viruses, cytomegalovirus, and human papillomavirus in patients receiving TNF-α blocking therapy, their implications in clinical practice, and possible preventative approach with vaccination. PMID:20142812

  11. Viral loads in dual infection with HIV-1 and cytomegalovirus

    PubMed Central

    Boriskin, Y.; Sharland, M.; Dalton, R.; duMont, G.; Booth, J.

    1999-01-01

    OBJECTIVE—A one year study of the relation between cytomegalovirus (CMV) and human immunodeficiency virus (HIV) viral loads in a cohort of children with vertically acquired HIV-1 infection.
DESIGN—Comparative analysis of viral load measurements for CMV and HIV-1 in peripheral blood leucocytes (PBLs) of individual children in relation to age and clinical staging.
METHODS—Nested polymerase chain reaction (PCR) was used to measure HIV-1 proviral DNA and CMV genomic DNA in PBLs of 56children.
RESULTS—The CMV load was highest in 0-2 year old HIV positive children with stage C disease (range, 1-7143 copies/100 ng DNA; median, 125) and was significantly lower in older children. Although higher in young children, HIV-1 viral load did not show the same marked reduction with age that is seen with CMV. Over a one year period, testing of serial samples for both viruses in a subgroup of children revealed a discordant relation between viral loads for CMV and HIV-1.
CONCLUSIONS—CMV viral load falls much faster than HIV viral load in dually infected children. Screening for clinical CMV disease is most likely to be of benefit in children under 2 years of age with stage C disease. In the few children studied, levels of CMV and HIV replication appear to be independent.

 PMID:10325727

  12. Immunohistochemistry in the diagnosis of cutaneous viral infections--part I. Cutaneous viral infections by herpesviruses and papillomaviruses.

    PubMed

    Molina-Ruiz, Ana M; Santonja, Carlos; Rütten, Arno; Cerroni, Lorenzo; Kutzner, Heinz; Requena, Luis

    2015-01-01

    Cutaneous viral infections are of increasing clinical importance, particularly in patients who are immunocompromised. The use of immunohistochemistry (IHC) in the diagnosis of cutaneous infections provides a rapid morphological diagnosis and can be applied to confirm the diagnosis of specific viral infections that may be difficult to diagnose with certainty using routine microscopy alone, thus facilitating clinical decisions in patient care. Several immunostains for specific viruses that have been useful in dermatopathology are reviewed. Emphasis is placed on new stains and novel uses of existing stains. This article is an up-to-date overview of the potential uses and limitations of IHC in the histopathologic diagnosis of cutaneous viral infections by herpesviruses and papillomaviruses. Whereas specific monoclonal antibodies effectively distinguish infections by herpes simplex virus-1, herpes simplex virus-2, varicella zoster virus, Epstein-Barr virus, and cytomegalovirus, IHC does not distinguish between the 120 antigenically distinct strains of human papillomavirus. IHC may assist dermatopathologists to appropriately diagnose viral infections caused by herpesviruses and papillomaviruses.

  13. Experimental models for hepatitis C viral infection.

    PubMed

    Boonstra, Andre; van der Laan, Luc J W; Vanwolleghem, Thomas; Janssen, Harry L A

    2009-11-01

    Hepatitis C virus (HCV) infection is a leading cause of chronic liver disease. The majority of infected individuals develop a persistent infection, which is associated with a high risk of liver cirrhosis and hepatocellular carcinoma. Since its discovery 20 years ago, progress in our understanding of this virus has been suboptimal due to the lack of good model systems. However, in the past decade this has greatly accelerated with the development of various in vitro cell culture systems and in vivo small-animal models. These systems have made a major impact on the field of HCV research, and have provided important breakthroughs in our understanding of HCV infection and replication. Importantly, the in vitro cell culture systems and the small-animal models have allowed preclinical testing of numerous novel antiviral compounds for the treatment of chronic HCV infection. In this article, we give an overview of current models, discuss their limitations, and provide future perspectives for research directed at the prevention and cure of hepatitis C.

  14. MAIT cells are activated during human viral infections.

    PubMed

    van Wilgenburg, Bonnie; Scherwitzl, Iris; Hutchinson, Edward C; Leng, Tianqi; Kurioka, Ayako; Kulicke, Corinna; de Lara, Catherine; Cole, Suzanne; Vasanawathana, Sirijitt; Limpitikul, Wannee; Malasit, Prida; Young, Duncan; Denney, Laura; Moore, Michael D; Fabris, Paolo; Giordani, Maria Teresa; Oo, Ye Htun; Laidlaw, Stephen M; Dustin, Lynn B; Ho, Ling-Pei; Thompson, Fiona M; Ramamurthy, Narayan; Mongkolsapaya, Juthathip; Willberg, Christian B; Screaton, Gavin R; Klenerman, Paul

    2016-06-23

    Mucosal-associated invariant T (MAIT) cells are abundant in humans and recognize bacterial ligands. Here, we demonstrate that MAIT cells are also activated during human viral infections in vivo. MAIT cells activation was observed during infection with dengue virus, hepatitis C virus and influenza virus. This activation-driving cytokine release and Granzyme B upregulation-is TCR-independent but dependent on IL-18 in synergy with IL-12, IL-15 and/or interferon-α/β. IL-18 levels and MAIT cell activation correlate with disease severity in acute dengue infection. Furthermore, HCV treatment with interferon-α leads to specific MAIT cell activation in vivo in parallel with an enhanced therapeutic response. Moreover, TCR-independent activation of MAIT cells leads to a reduction of HCV replication in vitro mediated by IFN-γ. Together these data demonstrate MAIT cells are activated following viral infections, and suggest a potential role in both host defence and immunopathology.

  15. Novel approaches and challenges to treatment of CNS viral infections

    PubMed Central

    Nath, Avindra; Tyler, Kenneth L.

    2014-01-01

    Existing and emerging viral CNS infections are major sources of human morbidity and mortality. Treatments of proven efficacy are currently limited predominantly to herpesviruses and human immunodeficiency virus. Development of new therapies has been hampered by the lack of appropriate animal model systems for some important viruses and by the difficulty in conducting human clinical trials for diseases that may be rare, or in the case of arboviral infections, often have variable seasonal and geographic incidence. Nonetheless, many novel approaches to antiviral therapy are available including candidate thiazolide and purazinecarboxamide derivatives with potential broad-spectrum antiviral efficacy. New herpesvirus drugs include viral helicase-primase and terminase inhibitors. The use of antisense oligonucleotides and other strategies to interfere with viral RNA translation has shown efficacy in experimental models of CNS viral disease. Identifying specific molecular targets within viral replication cycles has led to many existing antivirals and will undoubtedly continue to be the basis of future drug design. A promising new area of research involves therapies based on enhanced understanding of host antiviral immune responses. Toll-like receptor agonists, and drugs that inhibit specific cytokines as well as interferon preparations have all shown potential therapeutic efficacy. Passive transfer of virus-specific cytotoxic T-lymphocytes have been used in humans and may provide an effective therapies for some herpesvirus infections and potentially for progressive multifocal leukoencephalopathy. Humanized monoclonal antibodies directed against specific viral proteins have been developed and in several cases evaluated in humans in settings including West Nile virus and HIV infection and in pre-exposure prophylaxis for rabies. PMID:23913580

  16. Fc receptors in antibody-dependent enhancement of viral infections.

    PubMed

    Taylor, Adam; Foo, Suan-Sin; Bruzzone, Roberto; Dinh, Luan Vu; King, Nicholas J C; Mahalingam, Suresh

    2015-11-01

    Sensitization of the humoral immune response to invading viruses and production of antiviral antibodies forms part of the host antiviral repertoire. Paradoxically, for a number of viral pathogens, under certain conditions, antibodies provide an attractive means of enhanced virus entry and replication in a number of cell types. Known as antibody-dependent enhancement (ADE) of infection, the phenomenon occurs when virus-antibody immunocomplexes interact with cells bearing complement or Fc receptors, promoting internalization of the virus and increasing infection. Frequently associated with exacerbation of viral disease, ADE of infection presents a major obstacle to the prevention of viral disease by vaccination and is thought to be partly responsible for the adverse effects of novel antiviral therapeutics such as intravenous immunoglobulins. There is a growing body of work examining the intracellular signaling pathways and epitopes responsible for mediating ADE, with a view to aiding rational design of antiviral strategies. With in vitro studies also confirming ADE as a feature of infection for a growing number of viruses, challenges remain in understanding the multilayered molecular mechanisms of ADE and its effect on viral pathogenesis. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Respiratory viral infections occurring after hematopoietic stem cell transplantation.

    PubMed

    Seo, Sachiko

    Respiratory viral infection is one of the most crucial complications after hematopoietic stem cell transplantation (HSCT), which affects approximately 60% of HSCT recipients within one year after transplantation. Prevalence of progression from upper respiratory tract infection to lower respiratory tract disease (LRD) among HSCT recipients is 15-20% and day-90 mortality after LRD is as high as 40%. Risk factors for the progression to LRD are early infection after HSCT, low neutrophil or lymphocyte count, old age, and corticosteroid use. Aerosolized or oral ribavirin for respiratory syncytial virus infection and neuraminidase inhibitors for influenza are effective for the prevention of progression to LRD and mortality from LRD. Conversely, there are no definitive data concerning the efficacy of intravenous immunoglobulin. In cases of respiratory viral infection after HSCT, we recommend reduction of steroid dosage to less than 1 mg/kg/day, if applicable. Future directions for the management of respiratory viral infections in Japan are widespread availability of multiplex PCR testing and the introduction of new antiviral drugs.

  18. Acute disseminated encephalomyelitis in dengue viral infection.

    PubMed

    Wan Sulaiman, Wan Aliaa; Inche Mat, Liyana Najwa; Hashim, Hasnur Zaman; Hoo, Fan Kee; Ching, Siew Mooi; Vasudevan, Ramachandran; Mohamed, Mohd Hazmi; Basri, Hamidon

    2017-09-01

    Dengue is the most common arboviral disease affecting many countries worldwide. An RNA virus from the flaviviridae family, dengue has four antigenically distinct serotypes (DEN-1-DEN-4). Neurological involvement in dengue can be classified into dengue encephalopathy immune-mediated syndromes, encephalitis, neuromuscular or dengue muscle dysfunction and neuro-ophthalmic involvement. Acute disseminated encephalomyelitis (ADEM) is an immune mediated acute demyelinating disorder of the central nervous system following recent infection or vaccination. This monophasic illness is characterised by multifocal white matter involvement. Many dengue studies and case reports have linked ADEM with dengue virus infection but the association is still not clear. Therefore, this article is to review and discuss concerning ADEM in dengue as an immune-medicated neurological complication; and the management strategy required based on recent literature. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Slice Culture Modeling of Central Nervous System (CNS) Viral Infection

    PubMed Central

    Dionne, Kalen R.; Tyler, Kenneth L.

    2016-01-01

    The complexity of the central nervous system (CNS) is not recapitulated in cell culture models. Thin slicing and subsequent culture of CNS tissue has become a valued means to study neuronal and glial biology within the context of the physiologically relevant tissue milieu. Modern membrane-interface slice culturing methodology allows straightforward access to both CNS tissue and feeding medium, enabling experimental manipulations and analyses that would otherwise be impossible in vivo. CNS slices can be successfully maintained in culture for up to several weeks for investigation of evolving pathology and long-term intervention in models of chronic neurologic disease. Herein, membrane-interface slice culture models for studying viral encephalitis and myelitis are detailed, with emphasis on the use of these models for investigation of pathogenesis and evaluation of novel treatment strategies. We describe techniques to (1) generate brain and spinal cord slices from rodent donors, (2) virally infect slices, (3) monitor viral replication, (4) assess virally induced injury/apoptosis, (5) characterize “CNS-specific” cytokine production, and (6) treat slices with cytokines/pharmaceuticals. Although our focus is on CNS viral infection, we anticipate that the described methods can be adapted to address a wide range of investigations within the fields of neuropathology, neuroimmunology, and neuropharmacology. PMID:23975824

  20. Neuroinvasion and Inflammation in Viral Central Nervous System Infections

    PubMed Central

    Schroten, Horst

    2016-01-01

    Neurotropic viruses can cause devastating central nervous system (CNS) infections, especially in young children and the elderly. The blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB) have been described as relevant sites of entry for specific viruses as well as for leukocytes, which are recruited during the proinflammatory response in the course of CNS infection. In this review, we illustrate examples of established brain barrier models, in which the specific reaction patterns of different viral families can be analyzed. Furthermore, we highlight the pathogen specific array of cytokines and chemokines involved in immunological responses in viral CNS infections. We discuss in detail the link between specific cytokines and chemokines and leukocyte migration profiles. The thorough understanding of the complex and interrelated inflammatory mechanisms as well as identifying universal mediators promoting CNS inflammation is essential for the development of new diagnostic and treatment strategies. PMID:27313404

  1. Molecular Imaging of Influenza and Other Emerging Respiratory Viral Infections

    PubMed Central

    Lawler, James; Paragas, Jason; Jahrling, Peter B.; Mollura, Daniel J.

    2011-01-01

    Research on the pathogenesis and therapy of influenza and other emerging respiratory viral infections would be aided by methods that directly visualize pathophysiologic processes in patients and laboratory animals. At present, imaging of diseases, such as swine-origin H1N1 influenza, is largely restricted to chest radiograph and computed tomography (CT), which can detect pulmonary structural changes in severely ill patients but are more limited in characterizing the early stages of illness, differentiating inflammation from infection or tracking immune responses. In contrast, imaging modalities, such as positron emission tomography, single photon emission CT, magnetic resonance imaging, and bioluminescence imaging, which have become useful tools for investigating the pathogenesis of a range of disease processes, could be used to advance in vivo studies of respiratory viral infections in patients and animals. Molecular techniques might also be used to identify novel biomarkers of disease progression and to evaluate new therapies. PMID:21422476

  2. Within-host viral dynamics of dengue serotype 1 infection

    PubMed Central

    Clapham, Hannah E.; Tricou, Vianney; Van Vinh Chau, Nguyen; Simmons, Cameron P.; Ferguson, Neil M.

    2014-01-01

    Dengue, the most common mosquito-borne viral infection of humans, is endemic across much of the world, including much of tropical Asia and is increasing in its geographical range. Here, we present a mathematical model of dengue virus dynamics within infected individuals, detailing the interaction between virus and a simple immune response. We fit this model to measurements of plasma viral titre from cases of primary and secondary DENV 1 infection in Vietnam. We show that variation in model parameters governing the immune response is sufficient to create the observed variation in virus dynamics between individuals. Estimating model parameter values, we find parameter differences between primary and secondary cases consistent with the theory of antibody-dependent enhancement (namely enhanced rates of viral entry to target cells in secondary cases). Finally, we use our model to examine the potential impact of an antiviral drug on the within-host dynamics of dengue. We conclude that the impact of antiviral therapy on virus dynamics is likely to be limited if therapy is only started at the onset of symptoms, owing to the typically late stage of viral pathogenesis reached by the time symptoms are manifested and thus treatment is started. PMID:24829280

  3. Viral infections and the development of asthma in children

    PubMed Central

    2013-01-01

    Viral aetiology, host susceptibility (in particular allergic predisposition and sensitization), and illness severity, timing and frequency all appear to contribute as synergistic factors to the risk of developing asthma. Experimental models have shown both innate and adaptive immune responses contribute to this risk with lung inflammatory cells showing marked differences in phenotype and function in young compared with older animals, and these differences are further enhanced following virus infection. Findings to date strongly suggest that the impact of infant and preschool viral infections on the maturing immune system and developing lung that subsequently result in an asthma phenotype occur during a critical susceptibility period, and in a genetically susceptible host. There are currently no therapeutic strategies that allow primary or secondary prevention of asthma following early life viral respiratory infections in high-risk children, thus a focus on understanding the mechanisms of progression from viral wheezing in infants and preschool children to asthma development are urgently needed. This review summarizes the data reporting the role of the two most common viruses, that is, respiratory syncytial virus and human rhinovirus, that result in asthma development, comparing risk factors for disease progression, and providing insight into strategies that might be adopted to prevent asthma development. PMID:25165549

  4. Progress in the rapid diagnosis of viral infections: a Memorandum*

    PubMed Central

    1978-01-01

    This Memorandum reports the progress that has been made over the past year in the development of laboratory techniques for the rapid diagnosis of viral infections. Progress is reported in the use of the immunoperoxidase and immunofluorescence techniques for detecting viruses in respiratory secretions, the use of the glutaraldehyde and periodate methods for peroxidase conjugation, the application of enzyme immunoassay techniques in the detection of viral antigens and antibodies, and training in the use of these techniques. A number of recommendations for further research are made. PMID:352567

  5. Lymphatic Vessels Balance Viral Dissemination and Immune Activation following Cutaneous Viral Infection.

    PubMed

    Loo, Christopher P; Nelson, Nicholas A; Lane, Ryan S; Booth, Jamie L; Loprinzi Hardin, Sofia C; Thomas, Archana; Slifka, Mark K; Nolz, Jeffrey C; Lund, Amanda W

    2017-09-26

    Lymphatic vessels lie at the interface between peripheral sites of pathogen entry, adaptive immunity, and the systemic host. Though the paradigm is that their open structure allows for passive flow of infectious particles from peripheral tissues to lymphoid organs, virus applied to skin by scarification does not spread to draining lymph nodes. Using cutaneous infection by scarification, we analyzed the effect of viral infection on lymphatic transport and evaluated its role at the host-pathogen interface. We found that, in the absence of lymphatic vessels, canonical lymph-node-dependent immune induction was impaired, resulting in exacerbated pathology and compensatory, systemic priming. Furthermore, lymphatic vessels decouple fluid and cellular transport in an interferon-dependent manner, leading to viral sequestration while maintaining dendritic cell transport for immune induction. In conclusion, we found that lymphatic vessels balance immune activation and viral dissemination and act as an "innate-like" component of tissue host viral defense. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Dengue virus life cycle: viral and host factors modulating infectivity.

    PubMed

    Rodenhuis-Zybert, Izabela A; Wilschut, Jan; Smit, Jolanda M

    2010-08-01

    Dengue virus (DENV 1-4) represents a major emerging arthropod-borne pathogen. All four DENV serotypes are prevalent in the (sub) tropical regions of the world and infect 50-100 million individuals annually. Whereas the majority of DENV infections proceed asymptomatically or result in self-limited dengue fever, an increasing number of patients present more severe manifestations, such as dengue hemorrhagic fever and dengue shock syndrome. In this review we will give an overview of the infectious life cycle of DENV and will discuss the viral and host factors that are important in controlling DENV infection.

  7. Viral infections in goose flocks in Poland.

    PubMed

    Kozdruń, W; Woźniakowski, G; Samorek-Salamonowicz, E; Czekaj, H

    2012-01-01

    The aim of this study was to determine the infectious agents isolated from infection - suspected geese sent for the diagnostic examination to National Veterinary Research Institute. The birds were sent from goose flocks localized in different parts of Poland. Totally, 1,013 birds from 122 flocks were examined. The presence of goose parvovirus (GPV), goose haemorrhagic polyomavirus (GHPV), and goose circovirus (GoCV) was detected by triplex PCR. The presence of GPV DNA was shown in 36 flocks. The disease was most frequently diagnosed in goslings aging 3.5 weeks (ten flocks), and 2.5 weeks (six flocks). The analysis of the nucleotide sequence of VP1 encoding region has shown close similarity of Polish GPV strains within the group which ranged from 92% to 100%. Moreover, the similarity level of these strains with GPV isolated in Europe was from 91.3% to 100%. The occurrence of GoCV DNA was shown in 25 goose flocks. The presence of GoCV DNA was found among geese aged from 2 to 6 weeks, but predominantly in those aging 3.5 (three flocks) and 5 weeks (five flocks). The sequence analysis of PCR products from the sequenced region of ORFC1 capsid protein of GoCV has shown that Polish isolates share from 85% to 91% similarity with the sequences of GoCV strains isolated in other countries. The presence of DNA of GHPV was found in 3-week-old geese. During the last 2 years the presence of GHPV was confirmed in three flocks of goslings at the age from 3 to 3.5 weeks. During the last 12 years the occurrence of co-infection with GPV and GoCV was detected in six flocks aging from 5 to 6 weeks.

  8. Exosome Biogenesis, Regulation, and Function in Viral Infection

    PubMed Central

    Alenquer, Marta; Amorim, Maria João

    2015-01-01

    Exosomes are extracellular vesicles released upon fusion of multivesicular bodies (MVBs) with the cellular plasma membrane. They originate as intraluminal vesicles (ILVs) during the process of MVB formation. Exosomes were shown to contain selectively sorted functional proteins, lipids, and RNAs, mediating cell-to-cell communications and hence playing a role in the physiology of the healthy and diseased organism. Challenges in the field include the identification of mechanisms sustaining packaging of membrane-bound and soluble material to these vesicles and the understanding of the underlying processes directing MVBs for degradation or fusion with the plasma membrane. The investigation into the formation and roles of exosomes in viral infection is in its early years. Although still controversial, exosomes can, in principle, incorporate any functional factor, provided they have an appropriate sorting signal, and thus are prone to viral exploitation. This review initially focuses on the composition and biogenesis of exosomes. It then explores the regulatory mechanisms underlying their biogenesis. Exosomes are part of the endocytic system, which is tightly regulated and able to respond to several stimuli that lead to alterations in the composition of its sub-compartments. We discuss the current knowledge of how these changes affect exosomal release. We then summarize how different viruses exploit specific proteins of endocytic sub-compartments and speculate that it could interfere with exosome function, although no direct link between viral usage of the endocytic system and exosome release has yet been reported. Many recent reports have ascribed functions to exosomes released from cells infected with a variety of animal viruses, including viral spread, host immunity, and manipulation of the microenvironment, which are discussed. Given the ever-growing roles and importance of exosomes in viral infections, understanding what regulates their composition and levels, and

  9. Neurological diseases associated with viral and Mycoplasma pneumoniae infections

    PubMed Central

    Assaad, F.; Gispen, R.; Kleemola, M.; Syrůček, L.; Esteves, K.

    1980-01-01

    In 1963 the World Health Organization established a system for the collection and dissemination of information on viral infections and by 1976, laboratories in 49 countries were participating in this scheme. The present study is in two parts: part 1 is an analysis of almost 60 000 reports on neurological disease associated with viral and Mycoplasma pneumoniae infections reported during the 10-year period 1967-76. This analysis showed a steady increase in the yearly number of reports of viral neurological diseases, which closely followed the general increase in the overall reporting of virus diseases. Likewise, the seasonal pattern was similar to that seen in general for any given virus. Over 75% of the cases were in children. Over half of all viral neurological diseases were associated with enteroviruses, while the myxoviruses accounted for almost 30%. Among the myxoviruses, mumps virus was by far the most frequently reported. The polioviruses were the agents most commonly detected in cases of paralytic disease. The other enteroviruses, mumps virus, and the herpesviruses were the most frequently reported viruses in cases of aseptic meningitis or encephalitis. On the other hand, one-third to over one-half of the reports on the myxoviruses (excluding mumps and measles) related to ill-defined clinical conditions. Part 2 of the study deals in particular with viruses whose role in neurological disease is less well documented. One laboratory reported an outbreak of adenoviral aseptic meningitis in Czechoslovakia, while another described neurological disease associated with M. pneumoniae infection in Finland. Part 2 also includes a detailed appraisal of viral infections diagnosed in the Netherlands during the period 1973-76. The results are very similar to those routinely reported. PMID:6249511

  10. Exosome Biogenesis, Regulation, and Function in Viral Infection.

    PubMed

    Alenquer, Marta; Amorim, Maria João

    2015-09-17

    Exosomes are extracellular vesicles released upon fusion of multivesicular bodies(MVBs) with the cellular plasma membrane. They originate as intraluminal vesicles (ILVs) during the process of MVB formation. Exosomes were shown to contain selectively sorted functional proteins, lipids, and RNAs, mediating cell-to-cell communications and hence playing a role in the physiology of the healthy and diseased organism. Challenges in the field include the identification of mechanisms sustaining packaging of membrane-bound and soluble material to these vesicles and the understanding of the underlying processes directing MVBs for degradation or fusion with the plasma membrane. The investigation into the formation and roles of exosomes in viral infection is in its early years. Although still controversial, exosomes can, in principle, incorporate any functional factor, provided they have an appropriate sorting signal, and thus are prone to viral exploitation.This review initially focuses on the composition and biogenesis of exosomes. It then explores the regulatory mechanisms underlying their biogenesis. Exosomes are part of the endocytic system,which is tightly regulated and able to respond to several stimuli that lead to alterations in the composition of its sub-compartments. We discuss the current knowledge of how these changes affect exosomal release. We then summarize how different viruses exploit specific proteins of endocytic sub-compartments and speculate that it could interfere with exosome function, although no direct link between viral usage of the endocytic system and exosome release has yet been reported. Many recent reports have ascribed functions to exosomes released from cells infected with a variety of animal viruses, including viral spread, host immunity, and manipulation of the microenvironment, which are discussed. Given the ever-growing roles and importance of exosomes in viral infections, understanding what regulates their composition and levels, and

  11. West Nile viral infection of equids

    PubMed Central

    Angenvoort, J.; Brault, A.C.; Bowen, R.A.; Groschup, M.H.

    2015-01-01

    West Nile virus (WNV) is a flavivirus transmitted between certain species of birds and mosquito vectors. Tangential infections of equids and subsequent equine epizootics have occurred historically. Although the attack rate has been estimated to be below 10%, mortality rates can approach 50% in horses that present clinical disease. Symptoms are most commonly presenting in the form of encephalitis with ataxia as well as limb weakness, recumbency and muscle fasciculation. The most effective strategy for prevention of equine disease is proper vaccination with one of the numerous commercially available vaccines available in North America or the European Union. Recently, WNV has been increasingly associated with equine epizootics resulting from novel non-lineage-1a viruses in expanding geographic areas. However, specific experimental data on the virulence of these novel virus strains is lacking and questions remain as to the etiology of the expanded epizootics: whether it be a function of inherent virulence or ecological and/or climactic factors that could precipitate the altered epidemiological patterns observed. PMID:24035480

  12. Antiviral defense in shrimp: from innate immunity to viral infection.

    PubMed

    Wang, Pei-Hui; Huang, Tianzhi; Zhang, Xiaobo; He, Jian-Guo

    2014-08-01

    The culture of penaeid shrimp is rapidly developing as a major business endeavor worldwide. However, viral diseases have caused huge economic loss in penaeid shrimp culture industries. Knowledge of shrimp innate immunity and antiviral responses has made important progress in recent years, allowing the design of better strategies for the prevention and control of shrimp diseases. In this study, we have updated information on shrimp antiviral immunity and interactions between shrimp hosts and viral pathogens. Current knowledge and recent progress in immune signaling pathways (e.g., Toll/IMD-NF-κB and JAK-STAT signaling pathways), RNAi, phagocytosis, and apoptosis in shrimp antiviral immunity are discussed. The mechanism of viral infection in shrimp hosts and the interactions between viruses and shrimp innate immune systems are also analyzed. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Opioids and Viral Infections: A Double-Edged Sword

    PubMed Central

    Tahamtan, Alireza; Tavakoli-Yaraki, Masoumeh; Mokhtari-Azad, Talat; Teymoori-Rad, Majid; Bont, Louis; Shokri, Fazel; Salimi, Vahid

    2016-01-01

    Opioids and their receptors have received remarkable attention because they have the ability to alter immune function, which affects disease progression. In vitro and in vivo findings as well as observations in humans indicate that opioids and their receptors positively or negatively affect viral replication and virus-mediated pathology. The present study reviews recent insights in the role of opioids and their receptors in viral infections and discusses possible therapeutic opportunities. This review supports the emerging concept that opioids and their receptors have both favorable and unfavorable effects on viral disease, depending on the type of virus. Targeting of the opioid system is a potential option for developing effective therapies; however caution is required in relation to the beneficial functions of opioid systems. PMID:27446011

  14. Aptamers in Diagnostics and Treatment of Viral Infections

    PubMed Central

    Wandtke, Tomasz; Woźniak, Joanna; Kopiński, Piotr

    2015-01-01

    Aptamers are in vitro selected DNA or RNA molecules that are capable of binding a wide range of nucleic and non-nucleic acid molecules with high affinity and specificity. They have been conducted through the process known as SELEX (Systematic Evolution of Ligands by Exponential Enrichment). It serves to reach specificity and considerable affinity to target molecules, including those of viral origin, both proteins and nucleic acids. Properties of aptamers allow detecting virus infected cells or viruses themselves and make them competitive to monoclonal antibodies. Specific aptamers can be used to interfere in each stage of the viral replication cycle and also inhibit its penetration into cells. Many current studies have reported possible application of aptamers as a treatment or diagnostic tool in viral infections, e.g., HIV (Human Immunodeficiency Virus), HBV (Hepatitis B Virus), HCV (Hepatitis C Virus), SARS (Severe Acute Respiratory Syndrome), H5N1 avian influenza and recently spread Ebola. This review presents current developments of using aptamers in the diagnostics and treatment of viral diseases. PMID:25690797

  15. Chronic intestinal pseudo-obstruction related to viral infections.

    PubMed

    De Giorgio, R; Ricciardiello, L; Naponelli, V; Selgrad, M; Piazzi, G; Felicani, C; Serra, M; Fronzoni, L; Antonucci, A; Cogliandro, R F; Barbara, G; Corinaldesi, R; Tonini, M; Knowles, C H; Stanghellini, V

    2010-01-01

    Chronic intestinal pseudo-obstruction (CIPO), one of the most severe gastrointestinal motility disorders, is a condition characterized by a clinical picture mimicking small bowel occlusion with related symptoms and signs in the absence of demonstrable mechanical obstruction. Analysis of full-thickness biopsy samples may unravel structural changes of the neuromuscular layer involving the whole gut, although the midgut is usually worst affected. Intestinal pseudo-obstruction can occur in association with systemic neurological, endocrine, and connective tissue diseases or malignancy but, when no recognizable etiology is found, CIPO is referred to as idiopathic (CIIPO). The latter form can be diagnosed early in life due to a genetic etiology or in adulthood when a viral origin may be considered. This review addresses the hypothesis that some systemic neurotrophic viral infections can affect the enteric nervous system thereby altering normal peristaltic activity. Available data are reviewed, focusing specifically on herpesviruses or polyomaviruses (JC virus). These suggest that in comparison to a proportion of CIIPO patients, healthy controls rarely harbor viral DNA in the myenteric plexus, leaving open the possibility that a viral infection might have an etiologic role in the development of CIIPO. The review thus provides some new perspectives in the pathophysiology and perhaps targeted treatment of CIIPO.

  16. Cytokine-Mediated Activation of NK Cells during Viral Infection

    PubMed Central

    Freeman, Bailey E.; Raué, Hans-Peter; Hill, Ann B.

    2015-01-01

    ABSTRACT Natural killer (NK) cells provide a first line of defense against infection via the production of antiviral cytokines and direct lysis of target cells. Cytokines such as interleukin 12 (IL-12) and IL-18 are critical regulators of NK cell activation, but much remains to be learned about how cytokines interact to regulate NK cell function. Here, we have examined cytokine-mediated activation of NK cells during infection with two natural mouse pathogens, lymphocytic choriomeningitis virus (LCMV) and murine cytomegalovirus (MCMV). Using a systematic screen of 1,849 cytokine pairs, we identified the most potent combinations capable of eliciting gamma interferon (IFN-γ) production in NK cells. We observed that NK cell responses to cytokine stimulation were reduced 8 days after acute LCMV infection but recovered to preinfection levels by 60 days postinfection. In contrast, during MCMV infection, NK cell responses to cytokines remained robust at all time points examined. Ly49H-positive (Ly49H+) NK cells recognizing viral ligand m157 showed preferential proliferation during early MCMV infection. A population of these cells was still detected beyond 60 days postinfection, but these divided cells did not demonstrate enhanced IFN-γ production in response to innate cytokine stimulation. Instead, the maturation state of the NK cells (as determined by CD11b or CD27 surface phenotype) was predictive of responsiveness to cytokines, regardless of Ly49H expression. These results help define cytokine interactions that regulate NK cell activation and highlight variations in NK cell function during two unrelated viral infections. IMPORTANCE Natural killer cells play an important role in immunity to many viral infections. From an initial screen of 1,849 cytokine pairs, we identified the most stimulatory cytokine combinations capable of inducing IFN-γ production by NK cells. Ly49H+ NK cells, which can be directly activated by MCMV protein m157, preferentially proliferated

  17. Molecular mimicry in autoimmune neurological disease after viral infection.

    PubMed

    Roep, Bart O

    2003-10-01

    Viral infections have been associated with the development of several neurological and neuroendocrine autoimmune diseases. Structural similarities between environmental proteins and self-proteins have long been proposed to be targets for immune cross reactivity associated with initiation of autoimmune diseases. This mechanism called molecular mimicry has also been put forward for immune mediated neurological diseases associated with viral infection. Although many potential candidates for cross reactivity have been put forward, only few have been substantiated on the molecular level. For the definition of cellular immune cross-reactivity, it proved critical to appreciate that recognition patterns of T-cells are not linear. Subsequent microarray studies unequivocally demonstrated functional mimicry of seemingly disparate amino acid sequences. This review summarises the present evidence for molecular mimicry in neurological autoimmune diseases and virus

  18. Vaccine to Control the Viral Infection of Fish.

    DOEpatents

    Leong, JoAnn Ching

    1994-10-11

    Subunit vaccines and their use for immunizing fish against infection by viruses are disclosed. In particular, plasmid pG8 is constructed by joining, with the plasmid pUC8, DNA which encodes the glycoprotein of infectious hematopoietic necrosis virus (IHNV). E. coli cells are transformed by pG8, whereby pure viral antigen is produced to provide a vaccine for the control of IHNV in fish. 10 figs.

  19. Vaccine to control the viral infection of fish

    DOEpatents

    Leong, Jo-Ann C.

    1994-10-11

    Subunit vaccines and their use for immunizing fish against infection by viruses are disclosed. In particular, plasmid pG8 is constructed by joining, with the plasmid pUC8, DNA which encodes the glycoprotein of infectious hematopoietic necrosis virus (IHNV). E. coli cells are transformed by pG8, whereby pure viral antigen is produced to provide a vaccine for the control of IHNV in fish.

  20. Capsid-Targeted Viral Inactivation: A Novel Tactic for Inhibiting Replication in Viral Infections

    PubMed Central

    Zhang, Xingcui; Jia, Renyong; Zhou, Jiakun; Wang, Mingshu; Yin, Zhongqiong; Cheng, Anchun

    2016-01-01

    Capsid-targeted viral inactivation (CTVI), a conceptually powerful new antiviral strategy, is attracting increasing attention from researchers. Specifically, this strategy is based on fusion between the capsid protein of a virus and a crucial effector molecule, such as a nuclease (e.g., staphylococcal nuclease, Barrase, RNase HI), lipase, protease, or single-chain antibody (scAb). In general, capsid proteins have a major role in viral integration and assembly, and the effector molecule used in CTVI functions to degrade viral DNA/RNA or interfere with proper folding of viral key proteins, thereby affecting the infectivity of progeny viruses. Interestingly, such a capsid–enzyme fusion protein is incorporated into virions during packaging. CTVI is more efficient compared to other antiviral methods, and this approach is promising for antiviral prophylaxis and therapy. This review summarizes the mechanism and utility of CTVI and provides some successful applications of this strategy, with the ultimate goal of widely implementing CTVI in antiviral research. PMID:27657114

  1. Sunscreens Cause Coral Bleaching by Promoting Viral Infections

    PubMed Central

    Danovaro, Roberto; Bongiorni, Lucia; Corinaldesi, Cinzia; Giovannelli, Donato; Damiani, Elisabetta; Astolfi, Paola; Greci, Lucedio; Pusceddu, Antonio

    2008-01-01

    Background Coral bleaching (i.e., the release of coral symbiotic zooxanthellae) has negative impacts on biodiversity and functioning of reef ecosystems and their production of goods and services. This increasing world-wide phenomenon is associated with temperature anomalies, high irradiance, pollution, and bacterial diseases. Recently, it has been demonstrated that personal care products, including sunscreens, have an impact on aquatic organisms similar to that of other contaminants. Objectives Our goal was to evaluate the potential impact of sunscreen ingredients on hard corals and their symbiotic algae. Methods In situ and laboratory experiments were conducted in several tropical regions (the Atlantic, Indian, and Pacific Oceans, and the Red Sea) by supplementing coral branches with aliquots of sunscreens and common ultraviolet filters contained in sunscreen formula. Zooxanthellae were checked for viral infection by epifluorescence and transmission electron microscopy analyses. Results Sunscreens cause the rapid and complete bleaching of hard corals, even at extremely low concentrations. The effect of sunscreens is due to organic ultraviolet filters, which are able to induce the lytic viral cycle in symbiotic zooxanthellae with latent infections. Conclusions We conclude that sunscreens, by promoting viral infection, potentially play an important role in coral bleaching in areas prone to high levels of recreational use by humans. PMID:18414624

  2. Severe Hindrance of Viral Infection Propagation in Spatially Extended Hosts

    PubMed Central

    Capitán, José A.; Cuesta, José A.; Manrubia, Susanna C.; Aguirre, Jacobo

    2011-01-01

    The production of large progeny numbers affected by high mutation rates is a ubiquitous strategy of viruses, as it promotes quick adaptation and survival to changing environments. However, this situation often ushers in an arms race between the virus and the host cells. In this paper we investigate in depth a model for the dynamics of a phenotypically heterogeneous population of viruses whose propagation is limited to two-dimensional geometries, and where host cells are able to develop defenses against infection. Our analytical and numerical analyses are developed in close connection to directed percolation models. In fact, we show that making the space explicit in the model, which in turn amounts to reducing viral mobility and hindering the infective ability of the virus, connects our work with similar dynamical models that lie in the universality class of directed percolation. In addition, we use the fact that our model is a multicomponent generalization of the Domany-Kinzel probabilistic cellular automaton to employ several techniques developed in the past in that context, such as the two-site approximation to the extinction transition line. Our aim is to better understand propagation of viral infections with mobility restrictions, e.g., in crops or in plant leaves, in order to inspire new strategies for effective viral control. PMID:21912595

  3. Sunscreens cause coral bleaching by promoting viral infections.

    PubMed

    Danovaro, Roberto; Bongiorni, Lucia; Corinaldesi, Cinzia; Giovannelli, Donato; Damiani, Elisabetta; Astolfi, Paola; Greci, Lucedio; Pusceddu, Antonio

    2008-04-01

    Coral bleaching (i.e., the release of coral symbiotic zooxanthellae) has negative impacts on biodiversity and functioning of reef ecosystems and their production of goods and services. This increasing world-wide phenomenon is associated with temperature anomalies, high irradiance, pollution, and bacterial diseases. Recently, it has been demonstrated that personal care products, including sunscreens, have an impact on aquatic organisms similar to that of other contaminants. Our goal was to evaluate the potential impact of sunscreen ingredients on hard corals and their symbiotic algae. In situ and laboratory experiments were conducted in several tropical regions (the Atlantic, Indian, and Pacific Oceans, and the Red Sea) by supplementing coral branches with aliquots of sunscreens and common ultraviolet filters contained in sunscreen formula. Zooxanthellae were checked for viral infection by epifluorescence and transmission electron microscopy analyses. Sunscreens cause the rapid and complete bleaching of hard corals, even at extremely low concentrations. The effect of sunscreens is due to organic ultraviolet filters, which are able to induce the lytic viral cycle in symbiotic zooxanthellae with latent infections. We conclude that sunscreens, by promoting viral infection, potentially play an important role in coral bleaching in areas prone to high levels of recreational use by humans.

  4. Functional Role of Infective Viral Particles on Metal Reduction

    SciTech Connect

    Coates, John D.

    2014-04-01

    A proposed strategy for the remediation of uranium (U) contaminated sites was based on the immobilization of U by reducing the oxidized soluble U, U(VI), to form a reduced insoluble end product, U(IV). Previous studies identified Geobacter sp., including G. sulfurreducens and G. metallireducens, as predominant U(VI)-reducing bacteria under acetate-oxidizing and U(VI)-reducing conditions. Examination of the finished genome sequence annotation of the canonical metal reducing species Geobacter sulfurreducens strain PCA and G. metallireduceans strain GS-15 as well as the draft genome sequence of G. uraniumreducens strain Rf4 identified phage related proteins. In addition, the completed genome for Anaeromyxobacter dehalogenans and the draft genome sequence of Desulfovibrio desulfuricans strain G20, two more model metal-reducing bacteria, also revealed phage related sequences. The presence of these gene sequences indicated that Geobacter spp., Anaeromyxobacter spp., and Desulfovibrio spp. are susceptible to viral infection. Furthermore, viral populations in soils and sedimentary environments in the order of 6.4×10{sup 6}–2.7×10{sup 10} VLP’s cm{sup -3} have been observed. In some cases, viral populations exceed bacterial populations in these environments suggesting that a relationship may exist between viruses and bacteria. Our preliminary screens of samples collected from the ESR FRC indicated that viral like particles were observed in significant numbers. The objective of this study was to investigate the potential functional role viruses play in metal reduction specifically Fe(III) and U(VI) reduction, the environmental parameters affecting viral infection of metal reducing bacteria, and the subsequent effects on U transport.

  5. New Insights into IDO Biology in Bacterial and Viral Infections

    PubMed Central

    Schmidt, Susanne V.; Schultze, Joachim L.

    2014-01-01

    Initially, indoleamine-2,3-dioxygenase (IDO) has been introduced as a bactericidal effector mechanism and has been linked to T-cell immunosuppression and tolerance. In recent years, evidence has been accumulated that IDO also plays an important role during viral infections including HIV, influenza, and hepatitis B and C. Moreover, novel aspects about the role of IDO in bacterial infections and sepsis have been revealed. Here, we review these recent findings highlighting the central role of IDO and tryptophan metabolism in many major human infections. Moreover, we also shed light on issues concerning human-specific and mouse-specific host–pathogen interactions that need to be considered when studying the biology of IDO in the context of infections. PMID:25157255

  6. Experimental infection of mice with bovine viral diarrhea virus.

    PubMed

    Seong, Giyong; Oem, Jae-Ku; Lee, Kyung-Hyun; Choi, Kyoung-Seong

    2015-06-01

    The objective of this study was to test the ability of bovine viral diarrhea virus (BVDV) to infect mice. Two mice each were either mock infected or inoculated with one of three BVDV strains by the intraperitoneal (IP) (n = 8) or intranasal (IN) (n = 8) route. All mice were euthanized at day 7 postinfection (p.i.). None of the infected mice exhibited any clinical signs of illness; however, the tissues harvested after BVDV challenge showed significant histopathological changes. Blood samples from five mice that were injected IP and one mouse that was inoculated IN were positive for BVDV by reverse transcription polymerase chain reaction (RT-PCR). Immunohistochemistry (IHC) was used to assess the presence of viral antigen in the organs of mice infected with three BVDV strains. In IP-injected mice, BVDV antigen was detected in the spleen (5/6), mesenteric lymph nodes (4/6), lymphatic tissue of the lung (3/6), lung (1/6), and stomach (1/6) of the infected mice; however, it was not detected in the liver (0/6) or kidney (0/6). In IN-inoculated mice, BVDV antigen was detected in the lung and mesenteric lymph nodes of one BVDV-infected mouse but was not detected in other tissues. The results of this study suggest that the spleen is the most reliable tissue for BVDV antigen detection using IHC in the IP-injected group. Our study demonstrates that mice can be infected by BVDV. This is the first report of BVDV infection in mice.

  7. Estimating acute viral hepatitis infections from nationally reported cases.

    PubMed

    Klevens, R Monina; Liu, Stephen; Roberts, Henry; Jiles, Ruth B; Holmberg, Scott D

    2014-03-01

    Because only a fraction of patients with acute viral hepatitis A, B, and C are reported through national surveillance to the Centers for Disease Control and Prevention, we estimated the true numbers. We applied a simple probabilistic model to estimate the fraction of patients with acute hepatitis A, hepatitis B, and hepatitis C who would have been symptomatic, would have sought health care tests, and would have been reported to health officials in 2011. For hepatitis A, the frequencies of symptoms (85%), care seeking (88%), and reporting (69%) yielded an estimate of 2730 infections (2.0 infections per reported case). For hepatitis B, the frequencies of symptoms (39%), care seeking (88%), and reporting (45%) indicated 18 730 infections (6.5 infections per reported case). For hepatitis C, the frequency of symptoms among injection drug users (13%) and those infected otherwise (48%), proportion seeking care (88%), and percentage reported (53%) indicated 17 100 infections (12.3 infections per reported case). These adjustment factors will allow state and local health authorities to estimate acute hepatitis infections locally and plan prevention activities accordingly.

  8. Estimating Acute Viral Hepatitis Infections From Nationally Reported Cases

    PubMed Central

    Liu, Stephen; Roberts, Henry; Jiles, Ruth B.; Holmberg, Scott D.

    2014-01-01

    Objectives. Because only a fraction of patients with acute viral hepatitis A, B, and C are reported through national surveillance to the Centers for Disease Control and Prevention, we estimated the true numbers. Methods. We applied a simple probabilistic model to estimate the fraction of patients with acute hepatitis A, hepatitis B, and hepatitis C who would have been symptomatic, would have sought health care tests, and would have been reported to health officials in 2011. Results. For hepatitis A, the frequencies of symptoms (85%), care seeking (88%), and reporting (69%) yielded an estimate of 2730 infections (2.0 infections per reported case). For hepatitis B, the frequencies of symptoms (39%), care seeking (88%), and reporting (45%) indicated 18 730 infections (6.5 infections per reported case). For hepatitis C, the frequency of symptoms among injection drug users (13%) and those infected otherwise (48%), proportion seeking care (88%), and percentage reported (53%) indicated 17 100 infections (12.3 infections per reported case). Conclusions. These adjustment factors will allow state and local health authorities to estimate acute hepatitis infections locally and plan prevention activities accordingly. PMID:24432918

  9. Targeted DNA mutagenesis for the cure of chronic viral infections.

    PubMed

    Schiffer, Joshua T; Aubert, Martine; Weber, Nicholas D; Mintzer, Esther; Stone, Daniel; Jerome, Keith R

    2012-09-01

    Human immunodeficiency virus type 1 (HIV-1), hepatitis B virus (HBV), and herpes simplex virus (HSV) have been incurable to date because effective antiviral therapies target only replicating viruses and do not eradicate latently integrated or nonreplicating episomal viral genomes. Endonucleases that can target and cleave critical regions within latent viral genomes are currently in development. These enzymes are being engineered with high specificity such that off-target binding of cellular DNA will be absent or minimal. Imprecise nonhomologous-end-joining (NHEJ) DNA repair following repeated cleavage at the same critical site may permanently disrupt translation of essential viral proteins. We discuss the benefits and drawbacks of three types of DNA cleavage enzymes (zinc finger endonucleases, transcription activator-like [TAL] effector nucleases [TALENs], and homing endonucleases [also called meganucleases]), the development of delivery vectors for these enzymes, and potential obstacles for successful treatment of chronic viral infections. We then review issues regarding persistence of HIV-1, HBV, and HSV that are relevant to eradication with genome-altering approaches.

  10. Targeted DNA Mutagenesis for the Cure of Chronic Viral Infections

    PubMed Central

    Schiffer, Joshua T.; Aubert, Martine; Weber, Nicholas D.; Mintzer, Esther; Stone, Daniel

    2012-01-01

    Human immunodeficiency virus type 1 (HIV-1), hepatitis B virus (HBV), and herpes simplex virus (HSV) have been incurable to date because effective antiviral therapies target only replicating viruses and do not eradicate latently integrated or nonreplicating episomal viral genomes. Endonucleases that can target and cleave critical regions within latent viral genomes are currently in development. These enzymes are being engineered with high specificity such that off-target binding of cellular DNA will be absent or minimal. Imprecise nonhomologous-end-joining (NHEJ) DNA repair following repeated cleavage at the same critical site may permanently disrupt translation of essential viral proteins. We discuss the benefits and drawbacks of three types of DNA cleavage enzymes (zinc finger endonucleases, transcription activator-like [TAL] effector nucleases [TALENs], and homing endonucleases [also called meganucleases]), the development of delivery vectors for these enzymes, and potential obstacles for successful treatment of chronic viral infections. We then review issues regarding persistence of HIV-1, HBV, and HSV that are relevant to eradication with genome-altering approaches. PMID:22718830

  11. Congenital Cytomegalovirus Infection: Molecular Mechanisms Mediating Viral Pathogenesis

    PubMed Central

    Schleiss, Mark R.

    2013-01-01

    Human cytomegalovirus (CMV) is responsible for approximately 40,000 congenital infections in the United States each year. Congenital CMV disease frequently produces serious neurodevelopmental disability, as well as vision impairment and sensorineural hearing loss. Development of a CMV vaccine is therefore considered to be a major public health priority. The mechanisms by which CMV injures the fetus are complex and likely include a combination of direct fetal injury induced by pathologic virally-encoded gene products, an inability of the maternal immune response to control infection, and the direct impact of infection on placental function. CMV encodes gene products that function, both at the RNA and the protein level, to interfere with many cellular processes. These include gene products that modify the cell cycle; interfere with apoptosis; induce an inflammatory response; mediate vascular injury; induce site-specific breakage of chromosomes; promote oncogenesis; dysregulate cellular proliferation; and facilitate evasion of host immune responses. This minireview summarizes current concepts regarding these aspects of the molecular virology of CMV and the potential pathogenic impact of viral gene expression on the developing fetus. Areas for potential development of novel therapeutic intervention are suggested for improving the outcome of this disabling congenital infection. PMID:21827434

  12. Viral infection induces cytokine release by beta islet cells.

    PubMed Central

    Cavallo, M G; Baroni, M G; Toto, A; Gearing, A J; Forsey, T; Andreani, D; Thorpe, R; Pozzilli, P

    1992-01-01

    Viral infection has been suggested to play a triggering role in the pancreatic beta cell destruction which occurs in insulin-dependent diabetes (IDDM). However, the underlying mechanism of this phenomenon is unknown. In this study a human insulinoma cell line has been infected with measles, mumps and rubella viruses since a temporal association is reported between the clinical onset of IDDM and diseases caused by these viruses. The infection with measles and mumps viruses induced the release of interleukin-1 (IL-1) and interleukin-6 (IL-6) by the cell line as assessed by a bioassay and up-regulated the expression of human leucocyte antigen (HLA) class I and class II antigens as evaluated by cytofluorimetric analysis. Stimulation with rubella virus induced the release of IL-6 only and had no effect on HLA antigen expression. These data show for the first time that IL-1 and IL-6 secretion by an insulinoma cell line may occur after viral infection and suggest that cytokine release and increased expression of HLA molecules by beta cells may act to induce the immune response towards beta cells in IDDM. PMID:1592439

  13. Imaging CD8+ T cells during diverse viral infections

    PubMed Central

    Hickman, Heather D

    2015-01-01

    CD8+ T cells play a critical role in host defense against pathogens and tumors. Much of our current knowledge of the activation and subsequent effector activities of CD8+ T cells has been gained using ex vivo approaches examining the T cell population en masse for surface phenotype, activation status and the production of effector molecules. Thus, the precise behaviors and diversity of individual CD8+ T cells responding to virus infection in vivo have not been extensively explored, leaving many unanswered questions relevant to the rational design of antiviral vaccines and therapeutics. Recently, intravital multiphoton microscopy (MPM) has been used to image CD8+ T cell priming after infection with disparate viral pathogens ranging from small RNA viruses encoding few proteins to DNA viruses producing hundreds of viral proteins (many immunomodulatory). After priming, effector CD8+ T cells have been visualized in virus-infected tissue, both during primary infection and after transitioning to tissue resident memory cells (TRM). Here, I highlight recent advances in our understanding of antiviral CD8+ T cell responses revealed through intravital MPM. PMID:28243513

  14. Acute hemorrhagic encephalitis: An unusual presentation of dengue viral infection

    PubMed Central

    Nadarajah, Jeyaseelan; Madhusudhan, Kumble Seetharama; Yadav, Ajay Kumar; Gupta, Arun Kumar; Vikram, Naval Kumar

    2015-01-01

    Dengue is a common viral infection worldwide with presentation varying from clinically silent infection to dengue fever, dengue hemorrhagic fever, and severe fulminant dengue shock syndrome. Neurological manifestation usually results from multisystem dysfunction secondary to vascular leak. Presentation as hemorrhagic encephalitis is very rare. Here we present the case of a 13-year-old female admitted with generalized tonic clonic seizures. Plain computed tomography (CT) scan of head revealed hypodensities in bilateral deep gray matter nuclei and right posterior parietal lobe without any hemorrhage. Cerebrospinal fluid (CSF) and serology were positive for IgM and IgG antibodies to dengue viral antigen. Contrast-enhanced magnetic resonance imaging (MRI) revealed multifocal T2 and fluid attenuated inversion recovery (FLAIR) hyperintensities in bilateral cerebral parenchyma including basal ganglia. No hemorrhage was seen. She was managed with steroids. As her clinical condition deteriorated, after being stable for 2 days, repeat MRI was done which revealed development of hemorrhage within the lesions, and diagnosis of acute hemorrhagic encephalitis of dengue viral etiology was made. PMID:25709166

  15. Acute hemorrhagic encephalitis: An unusual presentation of dengue viral infection.

    PubMed

    Nadarajah, Jeyaseelan; Madhusudhan, Kumble Seetharama; Yadav, Ajay Kumar; Gupta, Arun Kumar; Vikram, Naval Kumar

    2015-01-01

    Dengue is a common viral infection worldwide with presentation varying from clinically silent infection to dengue fever, dengue hemorrhagic fever, and severe fulminant dengue shock syndrome. Neurological manifestation usually results from multisystem dysfunction secondary to vascular leak. Presentation as hemorrhagic encephalitis is very rare. Here we present the case of a 13-year-old female admitted with generalized tonic clonic seizures. Plain computed tomography (CT) scan of head revealed hypodensities in bilateral deep gray matter nuclei and right posterior parietal lobe without any hemorrhage. Cerebrospinal fluid (CSF) and serology were positive for IgM and IgG antibodies to dengue viral antigen. Contrast-enhanced magnetic resonance imaging (MRI) revealed multifocal T2 and fluid attenuated inversion recovery (FLAIR) hyperintensities in bilateral cerebral parenchyma including basal ganglia. No hemorrhage was seen. She was managed with steroids. As her clinical condition deteriorated, after being stable for 2 days, repeat MRI was done which revealed development of hemorrhage within the lesions, and diagnosis of acute hemorrhagic encephalitis of dengue viral etiology was made.

  16. Targeted Killing of Virally Infected Cells by Radiolabeled Antibodies to Viral Proteins

    PubMed Central

    Dadachova, Ekaterina; Patel, Mahesh C; Toussi, Sima; Apostolidis, Christos; Morgenstern, Alfred; Brechbiel, Martin W; Gorny, Miroslaw K; Zolla-Pazner, Susan; Casadevall, Arturo; Goldstein, Harris

    2006-01-01

    Background The HIV epidemic is a major threat to health in the developing and western worlds. A modality that targets and kills HIV-1-infected cells could have a major impact on the treatment of acute exposure and the elimination of persistent reservoirs of infected cells. The aim of this proof-of-principle study was to demonstrate the efficacy of a therapeutic strategy of targeting and eliminating HIV-1-infected cells with radiolabeled antibodies specific to viral proteins in vitro and in vivo. Methods and Findings Antibodies to HIV-1 envelope glycoproteins gp120 and gp41 labeled with radioisotopes bismuth 213 (213Bi) and rhenium 188 (188Re) selectively killed chronically HIV-1-infected human T cells and acutely HIV-1-infected human peripheral blood mononuclear cells (hPBMCs) in vitro. Treatment of severe combined immunodeficiency (SCID) mice harboring HIV-1-infected hPBMCs in their spleens with a 213Bi- or 188Re-labeled monoclonal antibody (mAb) to gp41 resulted in a 57% injected dose per gram uptake of radiolabeled mAb in the infected spleens and in a greater than 99% elimination of HIV-1-infected cells in a dose-dependent manner. The number of HIV-1-infected thymocytes decreased 2.5-fold in the human thymic implant grafts of SCID mice treated with the 188Re-labeled antibody to gp41 compared with those treated with the 188Re-control mAb. The treatment did not cause acute hematologic toxicity in the treated mice. Conclusions The current study demonstrates the effectiveness of HIV-targeted radioimmunotherapy and may provide a novel treatment option in combination with highly active antiretroviral therapy for the eradication of HIV. PMID:17090209

  17. Transmission spectroscopy of dengue viral infection Transmission spectroscopy of dengue viral infection

    NASA Astrophysics Data System (ADS)

    Firdous, S.; Ahmed, M.; Rehman, A.; Nawaz, M.; Anwar, S.; Murtaza, S.

    2012-04-01

    We presented the rapid diagnostic test for dengue infection based on light spectrum of human blood. The transmission spectra of dengue infected whole blood samples have been recorded in ultra violet to near infrared range (400 - 800 nm) of about 30 conformed infected patients and compared to normal blood samples. Transmission spectra of dengue infected blood illustrate a strong band from 400 - 600 nm with prominant peaks at 540 and 580 nm, where is in case of normal blood below 600 nm, total absorption has been observed. These prominent peaks from 400 - 600 nm are characteristics of cells damage and dangue virus antibodies immunoglobulin G (IgG) and immunoglobulin M (IgM) produced against dengue antigen. The presented diagnostic method is non invasive, cost effective, easy and fast screening technique for dengue infected patients.

  18. Emerging Viral Infections of the Central Nervous System

    PubMed Central

    Tyler, Kenneth L.

    2010-01-01

    In this 2-part review, I will focus on emerging virus infections of the central nervous system (CNS). Part 1 will introduce the basic features of emerging infections, including their definition, epidemiology, and the frequency of CNS involvement. Important mechanisms of emergence will be reviewed, including viruses spreading into new host ranges as exemplified by West Nile virus (WNV), Japanese encephalitis (JE) virus, Toscana virus, and enterovirus 71 (EV71). Emerging infections also result from opportunistic spread of viruses into known niches, often resulting from attenuated host resistance to infection. This process is exemplified by transplant-associated cases of viral CNS infection caused by WNV, rabies virus, lymphocytic choriomeningitis, and lymphocytic choriomeningitis–like viruses and by the syndrome of human herpesvirus 6 (HHV6)–associated posttransplantation acute limbic encephalitis. The second part of this review begins with a discussion of JC virus and the occurrence of progressive multifocal leukoencephalopathy in association with novel immunomodulatory therapies and then continues with an overview of the risk of infection introduced by imported animals (eg, monkeypox virus) and examples of emerging diseases caused by enhanced competence of viruses for vectors and the spread of vectors (eg, chikungunya virus) and then concludes with examples of novel viruses causing CNS infection as exemplified by Nipah and Hendra viruses and bat lyssaviruses. PMID:19667214

  19. Human NK Cell Diversity in Viral Infection: Ramifications of Ramification

    PubMed Central

    Strauss-Albee, Dara M.; Blish, Catherine A.

    2016-01-01

    Natural killer (NK) cells are a unique lymphocyte lineage with remarkable agility in the rapid destruction of virus-infected cells. They are also the most poorly understood class of lymphocyte. A spectrum of activating and inhibitory receptors at the NK cell surface leads to an unusual and difficult-to-study mechanism of cellular recognition, as well as a very high capacity for diversity at the single-cell level. Here, we review the evidence for the role of NK cells in the earliest stage of human viral infection, and in its prevention. We argue that single-cell diversity is a logical evolutionary adaptation for their position in the immune response and contributes to their ability to kill virus-infected cells. Finally, we look to the future, where emerging single-cell technologies will enable a new generation of rigorous and clinically relevant studies on NK cells accounting for all of their unique and diverse characteristics. PMID:26973646

  20. Stochastic extinction of viral infectivity through the action of defectors

    NASA Astrophysics Data System (ADS)

    Iranzo, J.; Manrubia, S. C.

    2009-01-01

    The high error rates of RNA viruses at replication suggest they might be close to the extinction threshold predicted by quasispecies theory. Hence, moderate increases in the mutation rate could drive them to extinction. In persistent infections of an RNA virus treated with a mutagen, it has been observed that infectivity eventually disappears, although the replicative ability of the virus is not affected. By means of a simple model that takes into account two phenotypic traits, we demonstrate that extinction is a purely stochastic phenomenon caused by the intermittent outbreaks of a defective, non-infective subpopulation. The transition between dynamics dominated by population fluctuations (finite system size N) and the mean-field behavior (N→∞) is characterized. We discuss the implications of this alternative pathway to viral extinction.

  1. Valacyclovir for the management of herpes viral infections.

    PubMed

    Chakrabarty, A; Anderson, N J; Beutner, R; Tyring, S K

    2005-02-01

    The Herpesviridae family (Types 1-8) continues to inflict considerable morbidity and social stigma upon humanity. Once infected with the herpes viruses, especially Types 1-3, they establish permanent residence within our nervous system and reactivate during periods of stress, trauma, and/or other precipitating factors. To date, there is no cure for herpes viral infections but antivirals can attenuate the symptoms and duration of episodic outbreaks. Prophylactic therapy can suppress recurrences. The first antiviral with selective activity against virus-infected cells is considered to be acyclovir. Our article will highlight the clinical indications of the current generation, valacyclovir, which is a prodrug of acyclovir. We consider valacyclovir as a second-generation antiviral, having taken into account the initial selectivity and safety profile of its progenitor, acyclovir.

  2. RNase L Activates the NLRP3 Inflammasome During Viral Infections

    PubMed Central

    Chakrabarti, Arindam; Banerjee, Shuvojit; Franchi, Luigi; Loo, Yueh-Ming; Gale, Michael; Núñez, Gabriel; Silverman, Robert H.

    2015-01-01

    SUMMARY The NLRP3 inflammasome assembles in response to danger signals, triggering self-cleavage of procaspase-1 and production of the proinflammatory cytokine IL-1β. Although virus infection activates the NLRP3 inflammasome, the underlying events remain incompletely understood. We report that virus activation of the NLRP3 inflammasome involves the 2′,5′-oligoadenylate (2-5A) synthetase (OAS)/RNase L system, a component of the interferon-induced antiviral response that senses double stranded RNA and activates endoribonuclease RNase L to cleave viral and cellular RNAs. The absence of RNase L reduces IL-1β production in influenza A virus-infected mice. RNA cleavage products generated by RNase L enhance IL-1β production but require the presence of 2′,3′-cyclic phosphorylated termini characteristic of RNase L activity. Additionally, these cleavage products stimulate NLRP3 complex formation with the DExD/H-box helicase, DHX33, and mitochondrial adapter protein, MAVS, which are each required for effective NLRP3 inflammasome activation. Thus, RNA cleavage events catalyzed by RNase L are required for optimal inflammasome activation during viral infections. PMID:25816776

  3. [Constrictive pericarditis as complication of viral respiratory infection].

    PubMed

    Darocha, Szymon; Paczek, Anna; Wawrzyńska, Liliana; Szturmowicz, Monika; Kober, Jarosław; Kurzyna, Marcin; Oniszh, Karina; Langfort, Renata; Litwiński, Paweł; Torbicki, Adam

    2012-01-01

    A 24 year-old man with 3-months medical history of recurrent respiratory infections and pericardial effusion, despite treatment with nonsteroid anti-inflammatory drugs, was admitted to the hospital with dyspnea on exertion. On admission he presented the symptoms of right heart insufficiency. Computed tomography of the chest demonstrated a thickened pericardium. Echocardiographic examination and right heart catheterisation established the diagnosis of constrictive pericarditis. Serologic tests suggested viral aetiology. The patient was referred to cardiothoracic surgery, partial pericardiectomy was performed with marked haemodynamic improvement.

  4. Viral co-infections are common and are associated with higher bacterial burden in children with clostridium difficile infection.

    PubMed

    El Feghaly, Rana E; Stauber, Jennifer L; Tarr, Phillip I; Haslam, David B

    2013-12-01

    Clostridium difficile infections in children are increasing. In this cohort study, we enrolled 62 children with diarrhea and C difficile. We performed polymerase chain reaction assays to detect viral agents of gastroenteritis and quantify C difficile burden. Fifteen (24%) children diagnosed as having C difficile infection had a concomitant viral co-infection. These patients tended to be younger and had a higher C difficile bacterial burden than children with no viral co-infections (median difference = 565,957 cfu/mL; P = 0.011), but were clinically indistinguishable. The contribution of viral co-infection to C difficile disease in children warrants future investigation.

  5. Type I IFN Signaling Is Dispensable during Secondary Viral Infection.

    PubMed

    Hosking, Martin P; Flynn, Claudia T; Whitton, J Lindsay

    2016-08-01

    Innate immune responses in general, and type I interferons (T1IFNs) in particular, play an important and often essential role during primary viral infections, by directly combatting the virus and by maximizing the primary adaptive immune response. Several studies have suggested that T1IFNs also contribute very substantially to the secondary (recall) response; they are thought (i) to be required to drive the early attrition of memory T cells, (ii) to support the subsequent expansion of surviving virus-specific memory cells, and (iii) to assist in the suppression and clearance of the infectious agent. However, many of these observations were predicated upon models in which T1IFN signaling was interrupted prior to a primary immune response, raising the possibility that the resulting memory cells might be intrinsically abnormal. We have directly addressed this by using an inducible-Cre model system in which the host remains genetically-intact during the primary response to infection, and in which T1IFN signaling can be effectively ablated prior to secondary viral challenge. We report that, in stark contrast to primary infection, T1IFN signaling is not required during the recall response. IFNαβR-deficient memory CD8+ and CD4+ memory T cells undergo attrition and expansion with kinetics that are indistinguishable from those of receptor-sufficient cells. Moreover, even in the absence of functional T1IFN signaling, the host's immune capacity to rapidly suppress, and then to eradicate, a secondary infection remains intact. Thus, this study shows that T1IFN signaling is dispensable during the recall response to a virus infection. Moreover, two broader implications may be drawn. First, a T cell's requirement for a cytokine is highly dependent on the cell's maturation / differentiation status. Consequently, second, these data underscore the importance of evaluating a gene's impact by modulating its expression or function in a temporally-controllable manner.

  6. Type I IFN Signaling Is Dispensable during Secondary Viral Infection

    PubMed Central

    Hosking, Martin P.; Flynn, Claudia T.; Whitton, J. Lindsay

    2016-01-01

    Innate immune responses in general, and type I interferons (T1IFNs) in particular, play an important and often essential role during primary viral infections, by directly combatting the virus and by maximizing the primary adaptive immune response. Several studies have suggested that T1IFNs also contribute very substantially to the secondary (recall) response; they are thought (i) to be required to drive the early attrition of memory T cells, (ii) to support the subsequent expansion of surviving virus-specific memory cells, and (iii) to assist in the suppression and clearance of the infectious agent. However, many of these observations were predicated upon models in which T1IFN signaling was interrupted prior to a primary immune response, raising the possibility that the resulting memory cells might be intrinsically abnormal. We have directly addressed this by using an inducible-Cre model system in which the host remains genetically-intact during the primary response to infection, and in which T1IFN signaling can be effectively ablated prior to secondary viral challenge. We report that, in stark contrast to primary infection, T1IFN signaling is not required during the recall response. IFNαβR-deficient memory CD8+ and CD4+ memory T cells undergo attrition and expansion with kinetics that are indistinguishable from those of receptor-sufficient cells. Moreover, even in the absence of functional T1IFN signaling, the host’s immune capacity to rapidly suppress, and then to eradicate, a secondary infection remains intact. Thus, this study shows that T1IFN signaling is dispensable during the recall response to a virus infection. Moreover, two broader implications may be drawn. First, a T cell’s requirement for a cytokine is highly dependent on the cell’s maturation / differentiation status. Consequently, second, these data underscore the importance of evaluating a gene’s impact by modulating its expression or function in a temporally-controllable manner. PMID

  7. [Progression of viral infection in twins born from a mother infected with human immunodeficiency virus].

    PubMed

    Gaggero, A; Escanilla, D; Larrañaga, C; Uribe, P; Espejo, R

    1995-10-01

    We studied the evolution of HIV-1 infection and immune response during six years in two twins born from an infected mother. The children had a continuous progression of the infection, proved by CD4+ cell count, serum anti-HIV antibodies, cultivable virus and proviral load. Now, both children are on antiviral treatment. The analysis of serum antibodies showed a different immune response in both children. One of them developed higher levels of antibodies directed against viral proteins and synthetic peptides derived from their aminoacid sequence. In this child, the amount of cultivable virus increased less than in his twin. Nucleotide sequencing of a part of viral genoma, showed that the virus belonged to the B subtype, prevalent in America and Europe. The observed differences in viral sequences suggest a different selective pressure in both twins. This phenomenon could be related to the observed differences in immune response.

  8. Hepatitis C viral infection as an associated risk factor for necrotizing fasciitis.

    PubMed

    Scher, Danielle; Kanlic, Enes; Bader, Julia; Ortiz, Melchor; Abdelgawad, Amr

    2012-04-01

    Necrotizing fasciitis is a rare soft tissue infection associated with a high mortality rate. Several risk factors for the development of necrotizing fasciitis have been studied, which has given surgeons insight into the types of patients who are more likely to present with this rapidly progressive infection. The concomitant diagnosis of hepatitis C viral infection has not been reported in the literature previously. In this retrospective study covering a 12-year period in 1 Level I trauma center, 10 (34%) of 29 patients presenting with necrotizing fasciitis had an underlying diagnosis of hepatitis C viral infection. The mortality rate in patients with hepatitis C viral infection was 30% compared with 21% for those without hepatitis C viral infection (P=.59). The proportion of patients presenting with the concomitant diagnosis of hepatitis C viral infection and necrotizing fasciitis was statistically greater than that expected from the prevalence of hepatitis C viral infection in the general population (1.8%; P<.001).Our study showed that hepatitis C viral infection is a risk factor for developing necrotizing fasciitis. Although our sample size was too small to show a statistical significance, we believe that a clinically significant increase in mortality of necrotizing fasciitis occurred in patients with concomitant hepatitis C viral infection. Therefore, the presence of hepatitis C viral infection in patients presenting with symptoms of necrotizing fasciitis should raise the clinical suspicion for this diagnosis, with the potential for a worse prognosis.

  9. Modelling HIV-RNA viral load in vertically infected children.

    PubMed

    Gray, Linsay; Cortina-Borja, Mario; Newell, Marie-Louise

    2004-03-15

    Human immunodeficiency virus (HIV) ribo-nucleic acid (RNA) viral load is a measure of actively replicating virus and is used as a marker of disease progression. For a thorough understanding of the dynamics of the evolution of the virus in the early life of HIV-1 vertically infected children, it is important to elucidate the pattern of HIV-RNA viral load over age. An aspect of assay systems used in the quantification of RNA viral load is that they measure values above particular cut-off values for detection, below which the assays used are not sufficiently sensitive. In this way, measurements are potentially left-censored. Recent adult studies suggest that to adequately model RNA pattern over age, it is necessary to account for within-subject correlation, due to repeated measures, and censoring. The aim of this study, therefore, was to establish whether it is necessary to use complex methods to allow for repeated measures within individuals and censoring of the HIV-RNA viral load in children enrolled in a cohort study. The approach involved the identification of an appropriate model for the basic pattern of RNA viral load by age and subsequent assessment of various estimation procedures accounting for repeated measures and censoring in different ways. Methods developed by Hughes involving the expectation-maximization (EM) algorithm and the Gibbs sampler were taken as the benchmark for comparison of simpler alternatives. Other approaches considered involve linear mixed-effects and ordinary least squares in which censoring is dealt with informally by taking the cut-off value as absolute or taking the mid-point between cut-off and zero. Fractional polynomials provided a substantially superior approach for modelling the dynamics of viral load over age compared to conventional polynomials or change-point models. Allowing for repeated measures was necessary to improve the power of the likelihood ratio tests required to establish the final model, but methods beyond taking

  10. Synaptic Plasticity and Neurological Disorders in Neurotropic Viral Infections

    PubMed Central

    Atluri, Venkata Subba Rao; Hidalgo, Melissa; Samikkannu, Thangavel; Kurapati, Kesava Rao Venkata; Nair, Madhavan

    2015-01-01

    Based on the type of cells or tissues they tend to harbor or attack, many of the viruses are characterized. But, in case of neurotropic viruses, it is not possible to classify them based on their tropism because many of them are not primarily neurotropic. While rabies and poliovirus are considered as strictly neurotropic, other neurotropic viruses involve nervous tissue only secondarily. Since the AIDS pandemic, the interest in neurotropic viral infections has become essential for all clinical neurologists. Although these neurotropic viruses are able to be harbored in or infect the nervous system, not all the neurotropic viruses have been reported to cause disrupted synaptic plasticity and impaired cognitive functions. In this review, we have discussed the neurotropic viruses, which play a major role in altered synaptic plasticity and neurological disorders. PMID:26649202

  11. Acute respiratory viral infections in pediatric cancer patients undergoing chemotherapy.

    PubMed

    Benites, Eliana C A; Cabrini, Dayane P; Silva, Andrea C B; Silva, Juliana C; Catalan, Daniel T; Berezin, Eitan N; Cardoso, Maria R A; Passos, Saulo D

    2014-01-01

    to estimate the prevalence of infection by respiratory viruses in pediatric patients with cancer and acute respiratory infection (ARI) and/or fever. cross-sectional study, from January 2011 to December 2012. The secretions of nasopharyngeal aspirates were analyzed in children younger than 21 years with acute respiratory infections. Patients were treated at the Grupo em Defesa da Criança Com Câncer (Grendacc) and University Hospital (HU), Jundiaí, SP. The rapid test was used for detection of influenza virus (Kit Biotrin, Inc. Ireland), and real-time multiplex polymerase chain reaction (FTD, Respiratory pathogens, multiplex Fast Trade Kit, Malta) for detection of influenza virus (H1N1, B), rhinovirus, parainfluenza virus, adenovirus, respiratory syncytial virus, human parechovirus, bocavirus, metapneumovirus, and human coronavirus. The prevalence of viral infection was estimated and association tests were used (χ(2) or Fisher's exact test). 104 samples of nasopharyngeal aspirate and blood were analyzed. The median age was 12 ± 5.2 years, 51% males, 68% whites, 32% had repeated ARIs, 32% prior antibiotic use, 19.8% cough, and 8% contact with ARIs. A total of 94.3% were in good general status. Acute lymphocytic leukemia (42.3%) was the most prevalent neoplasia. Respiratory viruses were detected in 50 samples: rhinoviruses (23.1%), respiratory syncytial virus AB (8.7%), and coronavirus (6.8%). Co-detection occurred in 19% of cases with 2 viruses and in 3% of those with 3 viruses, and was more frequent between rhinovirus and coronavirus 43. Fever in neutropenic patients was observed in 13%, of which four (30.7) were positive for viruses. There were no deaths. the prevalence of respiratory viruses was relevant in the infectious episode, with no increase in morbidity and mortality. Viral co-detection was frequent in patients with cancer and ARIs. Copyright © 2014 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  12. Viral Infection in Adults with Severe Acute Respiratory Infection in Colombia

    PubMed Central

    Remolina, Yuly Andrea; Ulloa, María Mercedes; Vargas, Hernán; Díaz, Liliana; Gómez, Sandra Liliana; Saavedra, Alfredo; Sánchez, Edgar; Cortés, Jorge Alberto

    2015-01-01

    Objectives To identify the viral aetiology in adult patients with severe acute respiratory infection (SARI) admitted to sentinel surveillance institutions in Bogotá in 2012. Design A cross-sectional study was conducted in which microarray molecular techniques for viral identification were used on nasopharyngeal samples of adult patients submitted to the surveillance system, and further descriptions of clinical features and relevant clinical outcomes, such as mortality, need for critical care, use of mechanical ventilation and hospital stay, were obtained. Setting Respiratory infections requiring hospital admission in surveillance centres in Bogotá, Colombia. Participants Ninety-one adult patients with acute respiratory infection (55% were female). Measurements Viral identification, intensive care unit admission, hospital stay, and mortality. Results Viral identification was achieved for 63 patients (69.2%). Comorbidity was frequently identified and mainly involved chronic pulmonary disease or pregnancy. Influenza, Bocavirus and Adenovirus were identified in 30.8%, 28.6% and 18.7% of the cases, respectively. Admission to the intensive care unit occurred in 42.9% of the cases, while mechanical ventilation was required for 36.3%. The average hospital stay was 9.9 days, and mortality was 15.4%. Antibiotics were empirically used in 90.1% of patients. Conclusions The prevalence of viral aetiology of SARI in this study was high, with adverse clinical outcomes, intensive care requirements and high mortality. PMID:26576054

  13. Sensors of Infection: Viral Nucleic Acid PRRs in Fish

    PubMed Central

    Poynter, Sarah; Lisser, Graeme; Monjo, Andrea; DeWitte-Orr, Stephanie

    2015-01-01

    Viruses produce nucleic acids during their replication, either during genomic replication or transcription. These nucleic acids are present in the cytoplasm or endosome of an infected cell, or in the extracellular space to be sensed by neighboring cells during lytic infections. Cells have mechanisms of sensing virus-generated nucleic acids; these nucleic acids act as flags to the cell, indicating an infection requiring defense mechanisms. The viral nucleic acids are called pathogen-associated molecular patterns (PAMPs) and the sensors that bind them are called pattern recognition receptors (PRRs). This review article focuses on the most recent findings regarding nucleic acids PRRs in fish, including: Toll-like receptors (TLRs), RIG-I-like receptors (RLRs), cytoplasmic DNA sensors (CDSs) and class A scavenger receptors (SR-As). It also discusses what is currently known of the downstream signaling molecules for each PRR family and the resulting antiviral response, either type I interferons (IFNs) or pro-inflammatory cytokine production. The review highlights what is known but also defines what still requires elucidation in this economically important animal. Understanding innate immune systems to virus infections will aid in the development of better antiviral therapies and vaccines for the future. PMID:26184332

  14. Nuclear domain 10 components upregulated via interferon during human cytomegalovirus infection potently regulate viral infection.

    PubMed

    Ashley, Caroline L; Glass, Mandy S; Abendroth, Allison; McSharry, Brian P; Slobedman, Barry

    2017-07-01

    Human cytomegalovirus (HCMV) is a ubiquitous betaherpesvirus that causes life-threatening disease in immunocompromised and immunonaïve individuals. Type I interferons (IFNs) are crucial molecules in the innate immune response to HCMV and are also known to upregulate several components of the interchromosomal multiprotein aggregates collectively referred to as nuclear domain 10 (ND10). In the context of herpesvirus infection, ND10 components are known to restrict gene expression. This raises the question as to whether key ND10 components (PML, Sp100 and hDaxx) act as anti-viral IFN-stimulated genes (ISGs) during HCMV infection. In this study, analysis of ND10 component transcription during HCMV infection demonstrated that PML and Sp100 were significantly upregulated whilst hDaxx expression remained unchanged. In cells engineered to block the production of, or response to, type I IFNs, upregulation of PML and Sp100 was not detected during HCMV infection. Furthermore, pre-treatment with an IFN-β neutralizing antibody inhibited upregulation of PML and Sp100 during both infection and treatment with HCMV-infected cell supernatant. The significance of ND10 components functioning as anti-viral ISGs during HCMV infection was determined through knockdown of PML, Sp100 and hDaxx. ND10 knockdown cells were significantly more permissive to HCMV infection, as previously described but, in contrast to control cells, could support HCMV plaque formation following IFN-β pre-treatment. This ability of HCMV to overcome the potently anti-viral effects of IFN-β in ND10 expression deficient cells provides evidence that ND10 component upregulation is a key mediator of the anti-viral activity of IFN-β.

  15. Mathematical models of immune effector responses to viral infections: Virus control versus the development of pathology

    NASA Astrophysics Data System (ADS)

    Wodarz, Dominik

    2005-12-01

    This article reviews mathematical models which have investigated the importance of lytic and non-lytic immune responses for the control of viral infections. Lytic immune responses fight the virus by killing infected cells, while non-lytic immune responses fight the virus by inhibiting viral replication while leaving the infected cell alive. The models suggest which types or combinations of immune responses are required to resolve infections which vary in their characteristics, such as the rate of viral replication and the rate of virus-induced target cell death. This framework is then applied to persistent infections and viral evolution. It is investigated how viral evolution and antigenic escape can influence the relative balance of lytic and non-lytic responses over time, and how this might correlate with the transition from an asymptomatic infection to pathology. This is discussed in the specific context of hepatitis C virus infection.

  16. Viral myocarditis: potential defense mechanisms within the cardiomyocyte against virus infection

    PubMed Central

    Yajima, Toshitaka

    2011-01-01

    Virus infection can inflict significant damage on cardiomyocytes through direct injury and secondary immune reactions, leading to myocarditis and dilated cardiomyopathy. While viral myocarditis or cardiomyopathy is a complication of systemic infection of cardiotropic viruses, most individuals infected with the viruses do not develop significant cardiac disease. However, some individuals proceed to develop severe virus-mediated heart disease. Recent studies have shown that viral infection of cardiomyocytes is required for the development of myocarditis and subsequent cardiomyopathy. This suggests that viral infection of cardiomyocytes can be an important step that determines the pathogenesis of viral myocarditis during systemic infection. Accordingly, this article focuses on potential defense mechanisms within the cardiomyocyte against virus infection. Understanding of the cardiomyocyte defense against invading viruses may give us novel insights into the pathophysiology of viral myocarditis, and enable us to develop innovative strategies of diagnosis and treatment for this challenging clinical entity. PMID:21585262

  17. Gene Expression Correlates with the Number of Herpes Viral Genomes Initiating Infection in Single Cells

    PubMed Central

    Cohen, Efrat M.

    2016-01-01

    Viral gene expression varies significantly among genetically identical cells. The sources of these variations are not well understood and have been suggested to involve both deterministic host differences and stochastic viral host interactions. For herpesviruses, only a limited number of incoming viral genomes initiate expression and replication in each infected cell. To elucidate the effect of this limited number of productively infecting genomes on viral gene expression in single cells, we constructed a set of fluorescence-expressing genetically tagged herpes recombinants. The number of different barcodes originating from a single cell is a good representative of the number of incoming viral genomes replicating (NOIVGR) in that cell. We identified a positive correlation between the NOIVGR and viral gene expression, as measured by the fluorescent protein expressed from the viral genome. This correlation was identified in three distinct cell-types, although the average NOIVGR per cell differed among these cell-types. Among clonal single cells, high housekeeping gene expression levels are not supportive of high viral gene expression, suggesting specific host determinants effecting viral infection. We developed a model to predict NOIVGR from cellular parameters, which supports the notion that viral gene expression is tightly linked to the NOIVGR in single-cells. Our results support the hypothesis that the stochastic nature of viral infection and host cell determinants contribute together to the variability observed among infected cells. PMID:27923068

  18. Gene Expression Correlates with the Number of Herpes Viral Genomes Initiating Infection in Single Cells.

    PubMed

    Cohen, Efrat M; Kobiler, Oren

    2016-12-01

    Viral gene expression varies significantly among genetically identical cells. The sources of these variations are not well understood and have been suggested to involve both deterministic host differences and stochastic viral host interactions. For herpesviruses, only a limited number of incoming viral genomes initiate expression and replication in each infected cell. To elucidate the effect of this limited number of productively infecting genomes on viral gene expression in single cells, we constructed a set of fluorescence-expressing genetically tagged herpes recombinants. The number of different barcodes originating from a single cell is a good representative of the number of incoming viral genomes replicating (NOIVGR) in that cell. We identified a positive correlation between the NOIVGR and viral gene expression, as measured by the fluorescent protein expressed from the viral genome. This correlation was identified in three distinct cell-types, although the average NOIVGR per cell differed among these cell-types. Among clonal single cells, high housekeeping gene expression levels are not supportive of high viral gene expression, suggesting specific host determinants effecting viral infection. We developed a model to predict NOIVGR from cellular parameters, which supports the notion that viral gene expression is tightly linked to the NOIVGR in single-cells. Our results support the hypothesis that the stochastic nature of viral infection and host cell determinants contribute together to the variability observed among infected cells.

  19. Transient Oral Human Cytomegalovirus Infections Indicate Inefficient Viral Spread from Very Few Initially Infected Cells.

    PubMed

    Mayer, Bryan T; Krantz, Elizabeth M; Swan, David; Ferrenberg, James; Simmons, Karen; Selke, Stacy; Huang, Meei-Li; Casper, Corey; Corey, Lawrence; Wald, Anna; Schiffer, Joshua T; Gantt, Soren

    2017-06-15

    Cytomegalovirus (CMV) is acquired by the oral route in children, and primary infection is associated with abundant mucosal replication, as well as the establishment of latency in myeloid cells that results in lifelong infection. The efficiency of primary CMV infection in humans following oral exposure, however, is unknown. We consistently detected self-limited, low-level oral CMV shedding events, which we termed transient CMV infections, in a prospective birth cohort of 30 highly exposed CMV-uninfected infants. We estimated the likelihood of transient oral CMV infections by comparing their observed frequency to that of established primary infections, characterized by persistent high-level shedding, viremia, and seroconversion. We developed mathematical models of viral dynamics upon initial oral CMV infection and validated them using clinical shedding data. Transient infections comprised 76 to 88% of oral CMV shedding events. For this high percentage of transient infections to occur, we identified two mathematical prerequisites: a very small number of initially infected oral cells (1 to 4) and low viral infectivity (<1.5 new cells infected/cell). These observations indicate that oral CMV infection in infants typically begins with a single virus that spreads inefficiently to neighboring cells. Thus, although the incidence of CMV infection is high during infancy, our data provide a mechanistic framework to explain why multiple CMV exposures are typically required before infection is successfully established. These findings imply that a sufficiently primed immune response could prevent CMV from establishing latent infection in humans and support the achievability of a prophylactic CMV vaccine.IMPORTANCE CMV infects the majority of the world's population and is a major cause of birth defects. Developing a vaccine to prevent CMV infection would be extremely valuable but would be facilitated by a better understanding of how natural human CMV infection is acquired. We

  20. Epidemiological investigation of selected pigeon viral infections in Poland.

    PubMed

    Stenzel, T A; Pestka, D; Tykałowski, B; Śmiałek, M; Koncicki, A

    2012-12-01

    Due to a lack of data in regard to the spread of viral infections in Polish pigeon populations, studies were undertaken to assess the frequency of adeno-, circo- and herpesvirus infections in flocks of pigeons across the entire country. In total, 107 flocks were examined, of which 61 per cent consisted of racing and 39 per cent of fancy pigeons. The flocks were divided into groups according to breed (racing and fancy pigeons) as well as physical condition (healthy and sick). In the studied pigeon flocks, the pigeon circovirus (PiCV) genetic material was the most frequently detected (44.5-100 per cent depending on the group), pigeon herpesvirus genetic material was second in frequency (0-30 per cent depending on the group), while genetic material of pigeon adenovirus was found only in two flocks of young birds with clinical symptoms of Young Pigeon Disease Syndrome (YPDS). The presence of fowl adenovirus (FAdV) genetic material was not detected in any of the studied flocks. Results obtained demonstrate a wide spread of circovirus in pigeon flocks in Poland, and substantiate earlier theories proposed by other authors, that immunosuppression evoked by PiCV infection is one of the main causative agents of YPDS.

  1. Interferon-Lambda: A Potent Regulator of Intestinal Viral Infections

    PubMed Central

    Lee, Sanghyun; Baldridge, Megan T.

    2017-01-01

    Interferon-lambda (IFN-λ) is a recently described cytokine found to be of critical importance in innate immune regulation of intestinal viruses. Endogenous IFN-λ has potent antiviral effects and has been shown to control multiple intestinal viruses and may represent a factor that contributes to human variability in response to infection. Importantly, recombinant IFN-λ has therapeutic potential against enteric viral infections, many of which lack other effective treatments. In this mini-review, we describe recent advances regarding IFN-λ-mediated regulation of enteric viruses with important clinical relevance including rotavirus, reovirus, and norovirus. We also briefly discuss IFN-λ interactions with other cytokines important in the intestine, and how IFN-λ may play a role in regulation of intestinal viruses by the commensal microbiome. Finally, we indicate currently outstanding questions regarding IFN-λ control of enteric infections that remain to be explored to enhance our understanding of this important immune molecule. PMID:28713375

  2. Viral respiratory infections among Hajj pilgrims in 2013.

    PubMed

    Barasheed, Osamah; Rashid, Harunor; Alfelali, Mohammad; Tashani, Mohamed; Azeem, Mohammad; Bokhary, Hamid; Kalantan, Nadeen; Samkari, Jamil; Heron, Leon; Kok, Jen; Taylor, Janette; El Bashir, Haitham; Memish, Ziad A; Haworth, Elizabeth; Holmes, Edward C; Dwyer, Dominic E; Asghar, Atif; Booy, Robert

    2014-12-01

    Middle East respiratory syndrome coronavirus (MERS-CoV) has emerged in the Arabian Gulf region, with its epicentre in Saudi Arabia, the host of the 'Hajj' which is the world's the largest mass gathering. Transmission of MERS-CoV at such an event could lead to its rapid worldwide dissemination. Therefore, we studied the frequency of viruses causing influenza-like illnesses (ILI) among participants in a randomised controlled trial at the Hajj 2013. We recruited 1038 pilgrims from Saudi Arabia, Australia and Qatar during the first day of Hajj and followed them closely for four days. A nasal swab was collected from each pilgrim who developed ILI. Respiratory viruses were detected using multiplex RT-PCR. ILI occurred in 112/1038 (11%) pilgrims. Their mean age was 35 years, 49 (44%) were male and 35 (31%) had received the influenza vaccine pre-Hajj. Forty two (38%) pilgrims had laboratory-confirmed viral infections; 28 (25%) rhinovirus, 5 (4%) influenza A, 2 (2%) adenovirus, 2 (2%) human coronavirus OC43/229E, 2 (2%) parainfluenza virus 3, 1 (1%) parainfluenza virus 1, and 2 (2%) dual infections. No MERS-CoV was detected in any sample. Rhinovirus was the commonest cause of ILI among Hajj pilgrims in 2013. Infection control and appropriate vaccination are necessary to prevent transmission of respiratory viruses at Hajj and other mass gatherings.

  3. THE INFLUENCE OF CORTISONE ON EXPERIMENTAL VIRAL INFECTION

    PubMed Central

    Smart, K. Marilyn; Kilbourne, Edwin D.

    1966-01-01

    The initial observations that cortisone may act as an inhibitor of viral interference (11, 4) are now explicable as an inhibitory effect on interferon synthesis. The suggestion that the action of interferon is also inhibited by cortisone or its analogues (6) has not been confirmed in a plaque reduction type of interferon assay system in which autointerference by the challenge inoculum is a lesser problem. In this respect, the present results are in accord with those obtained by DeMaeyer and DeMaeyer (8) with hydrocortisone in a system in which a low multiplicity (0.1) Sindbis virus infection in monolayer culture was employed with cytopathic effect (CPE) as an end-point. It has been shown that hydrocortisone is restrictive to the synthesis of interferon induced by inoculation of either infective or inactivated virus into the chick embryo, and that this inhibitory effect is temporary. However, in another study in the chick embryo, three spaced injections of hydrocortisone (0.25 mg/dose) prevented the appearance of detectable interferon during the entire 64 hr observation period following inoculation of 103.3 EID50 of Lee virus (12). The importance of explicit definition of experimental conditions in assessing hormonal effects on infection is illustrated by the capacity of hydrocortisone either to inhibit or increase interferon synthesis in vitro, depending on the proportion of inactivated and infective virus in the inoculum employed, and the time at which interferon is measured. As suggested previously, it is not unlikely that similar shifts in hormone-virus-interferon balance may operate in vivo to influence the outcome of infection. PMID:5905243

  4. [Viral respiratory tract infections in the Neonatal Intensive Care Unit].

    PubMed

    Gonzalez-Carrasco, E; Calvo, C; García-García, M L; Beato, M; Muñoz-Archidona, C; Pozo, F; Casas, I

    2015-04-01

    Viral respiratory infections cause major morbidity and mortality in preterm infants. We have performed a prospective study in our neonatal intensive care unit (NICU) to determine the incidence of respiratory infections, their impact and the epidemiology and outcome in high risk neonates. From September 2011 to May 2013 a prospective study was conducted in all preterm infants < 32 weeks gestational age and in all term newborns admitted to NICU for any pathology that are anticipated to have an income exceeding two weeks. A nasopharyngeal aspirate (NPA) was collected the first day of life and weekly until discharge for virologic study with polymerase chain reaction. When these babies presented respiratory symptoms a new NPA was collected in this moment. A clinical form was filled by the physician. A total of 60 infants were analyzed: 30 (50%) had a gestational age < 32 weeks and 36 (60%) weighing less than 1500 grams. We collected a total of 256 nasopharyngeal aspirate samples, 24 of them being positive (9.3%). These 24 positive samples corresponded to 13 infants in our cohort (21.6% of the patients). Of them, 9 were symptomatic and had 11 episodes of infection (2 patients had two different episodes with negative control between them). The most frequently identified virus was rhinovirus in (19) 79% of cases. The most frequent clinical data was the presence or increased of apneas (75%) and the needed of oxygenotherapy. HRV infections are prevalent in the NICU, and preterm infants have a high risk of infections with clinical relevance. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

  5. Designing therapeutic cancer vaccines by mimicking viral infections.

    PubMed

    Sultan, Hussein; Fesenkova, Valentyna I; Addis, Diane; Fan, Aaron E; Kumai, Takumi; Wu, Juan; Salazar, Andres M; Celis, Esteban

    2017-02-01

    The design of efficacious and cost-effective therapeutic vaccines against cancer remains both a research priority and a challenge. For more than a decade, our laboratory has been involved in the development of synthetic peptide-based anti-cancer therapeutic vaccines. We first dedicated our efforts in the identification and validation of peptide epitopes for both CD8 and CD4 T cells from tumor-associated antigens (TAAs). Because of suboptimal immune responses and lack of therapeutic benefit of peptide vaccines containing these epitopes, we have focused our recent efforts in optimizing peptide vaccinations in mouse tumor models using numerous TAA epitopes. In this focused research review, we describe how after taking lessons from the immune system's way of dealing with acute viral infections, we have designed peptide vaccination strategies capable of generating very high numbers of therapeutically effective CD8 T cells. We also discuss some of the remaining challenges to translate these findings into the clinical setting.

  6. Sex Drives Dimorphic Immune Responses to Viral Infections.

    PubMed

    Ghosh, Soumitra; Klein, Robyn S

    2017-03-01

    New attention to sexual dimorphism in normal mammalian physiology and disease has uncovered a previously unappreciated breadth of mechanisms by which females and males differentially exhibit quantitative phenotypes. Thus, in addition to the established modifying effects of hormones, which prenatally and postpubertally pattern cells and tissues in a sexually dimorphic fashion, sex differences are caused by extragonadal and dosage effects of genes encoded on sex chromosomes. Sex differences in immune responses, especially during autoimmunity, have been studied predominantly within the context of sex hormone effects. More recently, immune response genes have been localized to sex chromosomes themselves or found to be regulated by sex chromosome genes. Thus, understanding how sex impacts immunity requires the elucidation of complex interactions among sex hormones, sex chromosomes, and immune response genes. In this Brief Review, we discuss current knowledge and new insights into these intricate relationships in the context of viral infections.

  7. [Diagnosis and treatment of ocular viral infections in AIDS patients].

    PubMed

    Guex-Crosier, Y

    1998-11-01

    Ocular complication of AIDS are seen in about 75% of patients. Viral infections are predominant and can involve either external segment in the eye (Herpes type 8 in Kaposi sarcoma, molluscum contagiosum, Herpes simplex and zoster), or the posterior segment of the eye (CMV retinitis). The introduction of a Highly Active Antiretroviral Therapy (HAART) which associates two reverse transcriptase inhibitors and one antiprotease has changed the evolution of AIDS. The decrease of onset of CMV retinitis in AIDS patient is one of the best exemple. For the first time it was possible to stop the maintenance therapy against CMV retinitis in patients that have a sufficient increase in CD4+ cells and they did not present any relapse of CMV retinitis. But an increase of ocular inflammation can be observed with the onset of HAART such as uveitis or cystoid macular edema.

  8. Interferon at the crossroads of allergy and viral infections.

    PubMed

    Gonzales-van Horn, Sarah R; Farrar, J David

    2015-08-01

    IFN-α/β was first described as a potent inhibitor of viral replication, but it is now appreciated that IFN signaling plays a pleiotropic role in regulating peripheral T cell functions. Recently, IFN-α/β was shown to block human Th2 development by suppressing the transcription factor GATA3. This effect is consistent with the role for IFN-α/β in suppressing allergic inflammatory processes by blocking granulocyte activation and IL-4-mediated B cell isotype switching to IgE. With the consideration of recent studies demonstrating a defect in IFN-α/β secretion in DCs and epithelial cells from individuals with severe atopic diseases, there is an apparent reciprocal negative regulatory loop in atopic individuals, whereby the lack of IFN-α/β secretion by innate cells contributes to the development of allergic Th2 cells. Is it possible to overcome these events by treating with IFN-α/β or by inducing its secretion in vivo? In support of this approach, case studies have documented the therapeutic potential of IFN-α/β in treating steroid-resistant allergic asthma and other atopic diseases. Additionally, individuals with asthma who are infected with HCV and respond to IFN therapy showed a reduction in symptoms and severity of asthma attacks. These findings support a model, whereby allergic and antiviral responses are able to cross-regulate each other, as IgER cross-linking of pDCs prevents IFN-α/β production in response to viral infection. The clinical importance of upper-respiratory viruses in the context of allergic asthma supports the need to understand how these pathways intersect and to identify potential therapeutic targets.

  9. Sequential Bottlenecks Drive Viral Evolution in Early Acute Hepatitis C Virus Infection

    PubMed Central

    McElroy, Kerensa; Gaudieri, Silvana; Pham, Son T.; Chopra, Abha; Cameron, Barbara; Maher, Lisa; Dore, Gregory J.; White, Peter A.; Lloyd, Andrew R.

    2011-01-01

    Hepatitis C is a pandemic human RNA virus, which commonly causes chronic infection and liver disease. The characterization of viral populations that successfully initiate infection, and also those that drive progression to chronicity is instrumental for understanding pathogenesis and vaccine design. A comprehensive and longitudinal analysis of the viral population was conducted in four subjects followed from very early acute infection to resolution of disease outcome. By means of next generation sequencing (NGS) and standard cloning/Sanger sequencing, genetic diversity and viral variants were quantified over the course of the infection at frequencies as low as 0.1%. Phylogenetic analysis of reassembled viral variants revealed acute infection was dominated by two sequential bottleneck events, irrespective of subsequent chronicity or clearance. The first bottleneck was associated with transmission, with one to two viral variants successfully establishing infection. The second occurred approximately 100 days post-infection, and was characterized by a decline in viral diversity. In the two subjects who developed chronic infection, this second bottleneck was followed by the emergence of a new viral population, which evolved from the founder variants via a selective sweep with fixation in a small number of mutated sites. The diversity at sites with non-synonymous mutation was higher in predicted cytotoxic T cell epitopes, suggesting immune-driven evolution. These results provide the first detailed analysis of early within-host evolution of HCV, indicating strong selective forces limit viral evolution in the acute phase of infection. PMID:21912520

  10. Comparative transcriptome response in swine tracheobronchial lymph nodes to viral infection

    USDA-ARS?s Scientific Manuscript database

    The tracheobronchial lymph node (TBLN) transcriptome response was evaluated following viral infection using Digital Gene Expression Tag Profiling (DGETP). Pigs were sham-treated or infected intranasally with porcine reproductive and respiratory syndrome virus, porcine circovirus type 2, pseudorabies...

  11. Exacerbation of allergic inflammation in mice exposed to diesel exhaust particles prior to viral infection.

    EPA Science Inventory

    Background: Viral infections and exposure to oxidant air pollutants are two ofthe most important inducers ofasthma exacerbation. Our previous studies have demonstrated that exposure to diesel exhaust increases the susceptibility to influenza virus infections both in epithelial ce...

  12. Exacerbation of allergic inflammation in mice exposed to diesel exhaust particles prior to viral infection.

    EPA Science Inventory

    Background: Viral infections and exposure to oxidant air pollutants are two ofthe most important inducers ofasthma exacerbation. Our previous studies have demonstrated that exposure to diesel exhaust increases the susceptibility to influenza virus infections both in epithelial ce...

  13. Glycolytic control of vacuolar-type ATPase activity: a mechanism to regulate influenza viral infection.

    PubMed

    Kohio, Hinissan P; Adamson, Amy L

    2013-09-01

    As new influenza virus strains emerge, finding new mechanisms to control infection is imperative. In this study, we found that we could control influenza infection of mammalian cells by altering the level of glucose given to cells. Higher glucose concentrations induced a dose-specific increase in influenza infection. Linking influenza virus infection with glycolysis, we found that viral replication was significantly reduced after cells were treated with glycolytic inhibitors. Addition of extracellular ATP after glycolytic inhibition restored influenza infection. We also determined that higher levels of glucose promoted the assembly of the vacuolar-type ATPase within cells, and increased vacuolar-type ATPase proton-transport activity. The increase of viral infection via high glucose levels could be reversed by inhibition of the proton pump, linking glucose metabolism, vacuolar-type ATPase activity, and influenza viral infection. Taken together, we propose that altering glucose metabolism may be a potential new approach to inhibit influenza viral infection.

  14. Pseudo-nitzschia Challenged with Co-occurring Viral Communities Display Diverse Infection Phenotypes

    PubMed Central

    Carlson, Michael C. G.; McCary, Nicolette D.; Leach, Terence S.; Rocap, Gabrielle

    2016-01-01

    Viruses are catalysts of biogeochemical cycling, architects of microbial community structure, and terminators of phytoplankton blooms. Viral lysis of diatoms, a key group of eukaryotic phytoplankton, has the potential to impact carbon export and marine food webs. However, the impact of viruses on diatom abundance and community composition is unknown. Diatom-virus dynamics were explored by sampling every month at two coastal and estuarine locations in Washington state, USA resulting in 41 new isolates of the pennate diatom Pseudo-nitzschia and 20 environmental virus samples. We conducted a total of 820 pair-wise crosses of the Pseudo-nitzschia isolates and viral communities. Viral communities infected Pseudo-nitzschia isolates in 8% of the crosses overall and 16% of crosses when the host and viral communities were isolated from the same sample. Isolates ranged in their permissivity to infection with some isolates not infected by any viral samples and others infected by up to 10 viral communities. Isolates that were infected by the most viral communities also had the highest maximum observed viral titers (as high as 16000 infectious units ml-1). Titers of the viral communities were host dependent, as titers for one viral sample on eight different hosts spanned four orders of magnitude. Sequencing of the Pseudo-nitzschia Internal Transcribed Spacer 1 (ITS1) of the revealed multiple subgroups of hosts with 100% ITS1 identities that were infected by different viral communities. Indeed, we repeatedly isolated groups of isolates with identical ITS1 sequences from the same water sample that displayed different viral infection phenotypes. The interactions between Pseudo-nitzschia and the viral communities highlight the diversity of diatoms and emphasize the complexity and variability of diatom-virus dynamics in the ocean. PMID:27148216

  15. Pseudo-nitzschia Challenged with Co-occurring Viral Communities Display Diverse Infection Phenotypes.

    PubMed

    Carlson, Michael C G; McCary, Nicolette D; Leach, Terence S; Rocap, Gabrielle

    2016-01-01

    Viruses are catalysts of biogeochemical cycling, architects of microbial community structure, and terminators of phytoplankton blooms. Viral lysis of diatoms, a key group of eukaryotic phytoplankton, has the potential to impact carbon export and marine food webs. However, the impact of viruses on diatom abundance and community composition is unknown. Diatom-virus dynamics were explored by sampling every month at two coastal and estuarine locations in Washington state, USA resulting in 41 new isolates of the pennate diatom Pseudo-nitzschia and 20 environmental virus samples. We conducted a total of 820 pair-wise crosses of the Pseudo-nitzschia isolates and viral communities. Viral communities infected Pseudo-nitzschia isolates in 8% of the crosses overall and 16% of crosses when the host and viral communities were isolated from the same sample. Isolates ranged in their permissivity to infection with some isolates not infected by any viral samples and others infected by up to 10 viral communities. Isolates that were infected by the most viral communities also had the highest maximum observed viral titers (as high as 16000 infectious units ml(-1)). Titers of the viral communities were host dependent, as titers for one viral sample on eight different hosts spanned four orders of magnitude. Sequencing of the Pseudo-nitzschia Internal Transcribed Spacer 1 (ITS1) of the revealed multiple subgroups of hosts with 100% ITS1 identities that were infected by different viral communities. Indeed, we repeatedly isolated groups of isolates with identical ITS1 sequences from the same water sample that displayed different viral infection phenotypes. The interactions between Pseudo-nitzschia and the viral communities highlight the diversity of diatoms and emphasize the complexity and variability of diatom-virus dynamics in the ocean.

  16. Natural FCoV infection: cats with FIP exhibit significantly higher viral loads than healthy infected cats.

    PubMed

    Kipar, Anja; Baptiste, Keith; Barth, Andreas; Reinacher, Manfred

    2006-02-01

    Natural feline coronavirus (FCoV) infection has been shown to not only induce intestinal infection with viral shedding, but also systemic infection which either remains without clinical signs or leads to feline infectious peritonitis (FIP). As systemic infection is not the key event in the development of FIP, the question arises as to whether a potential difference in viral load might be of importance. Therefore, the purpose of this study was to quantitatively assess feline coronavirus (FCoV) RNA loads in haemolymphatic tissues of healthy, long-term FCoV-infected cats and cats with FIP. In cats that died from FIP, viral loads were significantly higher, indicating a higher rate of viral replication or a reduced capacity for viral clearance in cats developing and/or suffering from FIP.

  17. The stability analysis of a general viral infection model with distributed delays and multi-staged infected progression

    NASA Astrophysics Data System (ADS)

    Wang, Jinliang; Liu, Shengqiang

    2015-01-01

    We investigate an in-host model with general incidence and removal rate, as well as distributed delays in virus infections and in productions. By employing Lyapunov functionals and LaSalle's invariance principle, we define and prove the basic reproductive number R0 as a threshold quantity for stability of equilibria. It is shown that if R0 > 1 , then the infected equilibrium is globally asymptotically stable, while if R0 ⩽ 1 , then the infection free equilibrium is globally asymptotically stable under some reasonable assumptions. Moreover, n + 1 distributed delays describe (i) the time between viral entry and the transcription of viral RNA, (ii) the n - 1 -stage time needed for activated infected cells between viral RNA transcription and viral release, and (iii) the time necessary for the newly produced viruses to be infectious (maturation), respectively. The model can describe the viral infection dynamics of many viruses such as HIV-1, HCV and HBV.

  18. Glycolytic control of vacuolar-type ATPase activity: A mechanism to regulate influenza viral infection

    SciTech Connect

    Kohio, Hinissan P.; Adamson, Amy L.

    2013-09-15

    As new influenza virus strains emerge, finding new mechanisms to control infection is imperative. In this study, we found that we could control influenza infection of mammalian cells by altering the level of glucose given to cells. Higher glucose concentrations induced a dose-specific increase in influenza infection. Linking influenza virus infection with glycolysis, we found that viral replication was significantly reduced after cells were treated with glycolytic inhibitors. Addition of extracellular ATP after glycolytic inhibition restored influenza infection. We also determined that higher levels of glucose promoted the assembly of the vacuolar-type ATPase within cells, and increased vacuolar-type ATPase proton-transport activity. The increase of viral infection via high glucose levels could be reversed by inhibition of the proton pump, linking glucose metabolism, vacuolar-type ATPase activity, and influenza viral infection. Taken together, we propose that altering glucose metabolism may be a potential new approach to inhibit influenza viral infection. - Highlights: • Increased glucose levels increase Influenza A viral infection of MDCK cells. • Inhibition of the glycolytic enzyme hexokinase inhibited Influenza A viral infection. • Inhibition of hexokinase induced disassembly the V-ATPase. • Disassembly of the V-ATPase and Influenza A infection was bypassed with ATP. • The state of V-ATPase assembly correlated with Influenza A infection of cells.

  19. Papanicolaou smears induce partial immunity against sexually transmitted viral infections.

    PubMed

    Shapiro, Samuel; Hoffman, Margaret; Constant, Deborah; Rosenberg, Lynn; Carrara, Henri; Allan, Bruce Rider; Marais, Dianne Jean; Passmore, Jo-Ann Shelley; Williamson, Anna-Lise

    2007-11-01

    In a case-control study of hormonal contraceptives and invasive cervical cancer, an unexpected finding was a substantial decline in the prevalence of high-risk human papillomavirus (HPV) infection according to the lifetime number of Pap smears received. Here we assess the risk of 3 sexually transmitted viral infections -- herpes simplex virus 2 (HSV2), HPV, and human immunodeficiency virus (HIV) 1 and 2 -- in relation to the lifetime receipt of Pap smears. Stored sera taken from 1540 controls were tested for HSV2 and HIV; cervical scrapings were tested for HPV. Confounder-adjusted odds ratios for the lifetime receipt of Pap smears were estimated, relative to never having had a Papanicolau test. For ever-receipt of a Papanicolau test, the odds ratios for HSV2 and HPV were 0.7 (95% confidence interval = 0.5-0.9) and 0.5 (0.3-0.7), respectively, and there were dose-response trends according to the lifetime number of Pap smears received (test for trend P = 0.02 and 0.04, respectively). For HSV2 the odds ratios according to last receipt declined from 0.8 for 10 or more years previously to 0.4 for <1 year previously (trend P = 0.002). For HPV the ORs were 0.4 (0.3-0.7) for last receipt 5-9 years previously and 0.5 (0.4-0.8) for less than 5 years previously; for HIV the odds ratio for last receipt less than 5 years previously was 0.4 (0.3-0.9). For HSV2 and HIV the crude odds ratio estimates were systematically lower than the adjusted estimates, and residual confounding cannot be ruled out. In particular, the true number of sexual partners may have been under-reported, and there was no information on the sexual activity of the male partners, or on other health behaviors of the women or their partners. We hypothesize that Pap smears may provoke a short-term immune response against sexually transmitted viral infections.

  20. [Novel treatments for hepatitis C viral infection and the hepatic fibrosis].

    PubMed

    Lugo-Baruqui, Alejandro; Bautista López, Carlos Alfredo; Armendáriz-Borunda, Juan

    2009-02-01

    Hepatitis C virus (HCV) infection represents a global health problem due to its evolution to hepatic cirrhosis and hepatocellular carcinoma. The viral pathogenesis and infectious processes are not yet fully understood. The development of natural viral resistance towards the host immune system represents a mayor challenge for the design of alternative therapeutic interventions and development of viral vaccines. The molecular mechanisms of hepatic fibrosis are well described. New alternatives for the treatment of patients with HCV infection and hepatic cirrhosis are under intensive research. New drugs such as viral protease inhibitors and assembly inhibitors, as well as immune modulators have been studied in clinical trials. Additional alternatives include antifibrotic drugs, which reverse the hepatic cellular damage caused by HCV infection. This review makes reference to viral infective mechanisms, molecular pathways of liver fibrosis and overviews conventional and new treatments for HCV infection and liver fibrosis.

  1. Global Analysis of Viral Infection in an Archaeal Model System

    PubMed Central

    Maaty, Walid S.; Steffens, Joseph D.; Heinemann, Joshua; Ortmann, Alice C.; Reeves, Benjamin D.; Biswas, Swapan K.; Dratz, Edward A.; Grieco, Paul A.; Young, Mark J.; Bothner, Brian

    2012-01-01

    to viral infection, demonstrates the power of quantitative two-dimensional differential gel electrophoresis and ABPP using 2D gel compatible fluorescent dyes. PMID:23233852

  2. Brd4 Activates Early Viral Transcription upon Human Papillomavirus 18 Infection of Primary Keratinocytes

    PubMed Central

    McKinney, Caleb C.; Kim, Min Jung; Chen, Dan

    2016-01-01

    ABSTRACT  Human papillomaviruses (HPVs) replicate in the cutaneous and mucosal epithelia, and the infectious cycle is synchronous with the differentiation program of the host keratinocytes. The virus initially infects dividing cells in the lower layers of the epithelium, where it establishes a persistent infection. The viral genome is maintained as a low-copy-number, extrachromosomal element in these proliferating cells but switches to the late stage of the life cycle in differentiated cells. The cellular chromatin adaptor protein Brd4 is involved in several stages and processes of the viral life cycle. In concert with the viral transcriptional regulator E2, Brd4 can repress transcription from the early viral promoter. Brd4 and E2 form a complex with the viral genome that associates with host chromosomes to partition the viral genome in dividing cells; Brd4 also localizes to active sites of productive HPV DNA replication. However, because of the difficulties in producing HPV viral particles, the role of Brd4 in modulating viral transcription and replication at the initial stage of infection is unclear. In this study, we have used an HPV18 quasivirus-based genome delivery system to assess the role of Brd4 in the initial infectivity of primary human keratinocytes. We show that, upon infection of primary human keratinocytes with HPV18 quasivirus, Brd4 activates viral transcription and replication. Furthermore, this activation is independent of the functional interaction between Brd4 and the HPV18 E2 protein. PMID:27879331

  3. Clinical Impact of Mixed Respiratory Viral Infection in Children with Adenoviral Infection

    PubMed Central

    Seo, Young Eun

    2016-01-01

    Background Although adenovirus (ADV) infection occurs steadily all year round in Korea and the identification of respiratory viral coinfections has been increasing following the introduction of multiplex real-time polymerase chain reaction tests, the clinical impact of viral coinfection in children with ADV infection has rarely been reported. Materials and Methods Medical records of children diagnosed with ADV infection were retrospectively reviewed. The enrolled children were divided into two groups based on the identified respiratory viruses: ADV group and coinfection group. Clinical and laboratory parameters were compared between the two groups. Results In total, 105 children (60 males and 45 females) with a median age of 29 months (range: 0-131 months) diagnosed with an ADV infection were enrolled. Fever (99.0%) was by far the most frequent symptom, followed by respiratory (82.9%), and gastrointestinal (22.9%) symptoms. Upper and lower respiratory tract infections were diagnosed in 56 (53.3%), and 32 (30.5%) children, respectively. Five (4.8%) children received oxygen therapy, and no child died due to ADV infection. Coinfection was diagnosed in 32 (30.5%) children, with rhinovirus (46.9%), and respiratory syncytial virus (21.9%) being the most frequent. The proportions of children younger than 24 months (P <0.001), with underlying medical conditions (P = 0.020), and diagnosed with lower respiratory tract infection (P = 0.011) were significantly higher in the coinfection group than in the ADV group. In a multivariate analysis, only the younger age was significantly associated with coinfection (P <0.001). Although more children in the coinfection group received oxygen therapy (P = 0.029), the duration of fever and hospitalization was not significantly different between the two groups. Conclusion Respiratory viral coinfection with ADV occurred more frequently in children younger than 24 months of age compared with children aged 24 months or older. Respiratory

  4. The implications of viral reservoirs on the elite control of HIV-1 infection.

    PubMed

    Buckheit, Robert W; Salgado, Maria; Martins, Karen O; Blankson, Joel N

    2013-03-01

    The mechanisms by which a small percentage of HIV-1 infected individuals known as elite suppressors or controllers are able to control viral replication are not fully understood. Early cases of viremic control were attributed to infection with defective virus, but subsequent work has demonstrated that infection with a defective virus is not the exclusive cause of control. Replication-competent virus has been isolated from patients who control viral replication, and studies have demonstrated that evolution occurs in plasma virus but not in virus isolates from the latent reservoir. Additionally, transmission pair studies have demonstrated that patients infected with similar viruses can have dramatically different outcomes of infection. An increased understanding of the viral factors associated with control is important to understand the interplay between viral replication and host control, and has implications for the design of an effective therapeutic vaccine that can lead to a functional cure of HIV-1 infection.

  5. Emergence of distinct multi-armed immunoregulatory antigen presenting cells during persistent viral infection

    PubMed Central

    Wilson, Elizabeth B.; Kidani, Yoko; Elsaesser, Heidi; Barnard, Jennifer; Raff, Laura; Karp, Christopher L.; Bensinger, Steven; Brooks, David G.

    2012-01-01

    During persistent viral infection, adaptive immune responses are suppressed by immunoregulatory factors, contributing to viral persistence. Although this suppression is mediated by inhibitory factors, the mechanisms by which virus-specific T cells encounter and integrate immunoregulatory signals during persistent infection are unclear. We show that a distinct population of IL-10-expressing immunoregulatory antigen presenting cells (APC) is amplified during chronic versus acute lymphocytic choriomeningitis virus (LCMV) infection and suppresses T cell responses. Although acute LCMV infection induces the expansion of immunoregulatory APC, they subsequently decline. However, during persistent LCMV infection, immunoregulatory APC are amplified and parallel the viral replication kinetics. Further characterization demonstrates that immunoregulatory APC are molecularly and metabolically distinct, and exhibit increased expression of T cell-interacting molecules and negative regulatory factors that suppress T cell responses. Thus, immunoregulatory APC are amplified during viral persistence and deliver inhibitory signals that suppress antiviral T cell immunity and likely contribute to persistent infection. PMID:22607801

  6. DNA cleavage enzymes for treatment of persistent viral infections: Recent advances and the pathway forward

    SciTech Connect

    Weber, Nicholas D.; Aubert, Martine; Dang, Chung H.; Stone, Daniel; Jerome, Keith R.

    2014-04-15

    Treatment for most persistent viral infections consists of palliative drug options rather than curative approaches. This is often because long-lasting viral DNA in infected cells is not affected by current antivirals, providing a source for viral persistence and reactivation. Targeting latent viral DNA itself could therefore provide a basis for novel curative strategies. DNA cleavage enzymes can be used to induce targeted mutagenesis of specific genes, including those of exogenous viruses. Although initial in vitro and even in vivo studies have been carried out using DNA cleavage enzymes targeting various viruses, many questions still remain concerning the feasibility of these strategies as they transition into preclinical research. Here, we review the most recent findings on DNA cleavage enzymes for human viral infections, consider the most relevant animal models for several human viral infections, and address issues regarding safety and enzyme delivery. Results from well-designed in vivo studies will ideally provide answers to the most urgent remaining questions, and allow continued progress toward clinical application. - Highlights: • Recent in vitro and in vivo results for DNA cleavage enzymes targeting persistent viral infections. • Analysis of the best animal models for testing enzymes for HBV, HSV, HIV and HPV. • Challenges facing in vivo delivery of therapeutic enzymes for persistent viral infections. • Safety issues to be addressed with proper animal studies.

  7. Viral Cyclins Mediate Separate Phases of Infection by Integrating Functions of Distinct Mammalian Cyclins

    PubMed Central

    Lee, Katherine S.; Suarez, Andrea L.; Claypool, David J.; Armstrong, Taylor K.; Buckingham, Erin M.; van Dyk, Linda F.

    2012-01-01

    Gammaherpesvirus cyclins have expanded biochemical features relative to mammalian cyclins, and promote infection and pathogenesis including acute lung infection, viral persistence, and reactivation from latency. To define the essential features of the viral cyclin, we generated a panel of knock-in viruses expressing various viral or mammalian cyclins from the murine gammaherpesvirus 68 cyclin locus. Viral cyclins of both gammaherpesvirus 68 and Kaposi's sarcoma-associated herpesvirus supported all cyclin-dependent stages of infection, indicating functional conservation. Although mammalian cyclins could not restore lung replication, they did promote viral persistence and reactivation. Strikingly, distinct and non-overlapping mammalian cyclins complemented persistence (cyclin A, E) or reactivation from latency (cyclin D3). Based on these data, unique biochemical features of viral cyclins (e.g. enhanced kinase activation) are not essential to mediate specific processes during infection. What is essential for, and unique to, the viral cyclins is the integration of the activities of several different mammalian cyclins, which allows viral cyclins to mediate multiple, discrete stages of infection. These studies also demonstrated that closely related stages of infection, that are cyclin-dependent, are in fact genetically distinct, and thus predict that cyclin requirements may be used to tailor potential therapies for virus-associated diseases. PMID:22319441

  8. Viral Infection in the Development and Progression of Pediatric Acute Respiratory Distress Syndrome.

    PubMed

    Nye, Steven; Whitley, Richard J; Kong, Michele

    2016-01-01

    Viral infections are an important cause of pediatric acute respiratory distress syndrome (ARDS). Numerous viruses, including respiratory syncytial virus (RSV) and influenza A (H1N1) virus, have been implicated in the progression of pneumonia to ARDS; yet the incidence of progression is unknown. Despite acute and chronic morbidity associated with respiratory viral infections, particularly in "at risk" populations, treatment options are limited. Thus, with few exceptions, care is symptomatic. In addition, mortality rates for viral-related ARDS have yet to be determined. This review outlines what is known about ARDS secondary to viral infections including the epidemiology, the pathophysiology, and diagnosis. In addition, emerging treatment options to prevent infection, and to decrease disease burden will be outlined. We focused on RSV and influenza A (H1N1) viral-induced ARDS, as these are the most common viruses leading to pediatric ARDS, and have specific prophylactic and definitive treatment options.

  9. Clinical guidelines for the management of acute viral infections in patients with systemic lupus erythematosus.

    PubMed

    Ramos-Casals, M; Cuadrado, M J; Alba, P; Sanna, G; Brito-Zerón, P; Bertolaccini, L; Babini, A; Moreno, A; D'Cruz, D; Khamashta, M A

    2009-12-01

    In recent decades, many research groups have focused on the role of viral infections in the etiopathogenesis of systemic lupus erythematosus (SLE), the so-called "viral hypothesis". The main candidates are herpes viruses such as Epstein-Barr virus (EBV) and cytomegalovirus (CMV), which have a high seroprevalence in the general population. However, a viral causal agent of SLE has not yet been discovered, although many interesting clinical findings on the complex interactions between viruses and SLE have been made. This review analyzes 88 cases of acute viral infections in adult patients with SLE and identifies situations in which viral infections influenced the diagnosis, prognosis or treatment of SLE. We also propose clinical guidelines for the management of these infections in patients with SLE.

  10. Viral Infection in the Development and Progression of Pediatric Acute Respiratory Distress Syndrome

    PubMed Central

    Nye, Steven; Whitley, Richard J.; Kong, Michele

    2016-01-01

    Viral infections are an important cause of pediatric acute respiratory distress syndrome (ARDS). Numerous viruses, including respiratory syncytial virus (RSV) and influenza A (H1N1) virus, have been implicated in the progression of pneumonia to ARDS; yet the incidence of progression is unknown. Despite acute and chronic morbidity associated with respiratory viral infections, particularly in “at risk” populations, treatment options are limited. Thus, with few exceptions, care is symptomatic. In addition, mortality rates for viral-related ARDS have yet to be determined. This review outlines what is known about ARDS secondary to viral infections including the epidemiology, the pathophysiology, and diagnosis. In addition, emerging treatment options to prevent infection, and to decrease disease burden will be outlined. We focused on RSV and influenza A (H1N1) viral-induced ARDS, as these are the most common viruses leading to pediatric ARDS, and have specific prophylactic and definitive treatment options. PMID:27933286

  11. Factors affecting responses to murine oncogenic viral infections.

    PubMed Central

    Harvey, J. J.; Rager-Zisman, B.; Wheelock, E. F.; Nevin, P. A.

    1980-01-01

    Silica specifically kills macrophages in vitro, and in vivo has been used as a method of determining the possible immunological or other roles of macrophages in a number of viral infections. In experiments reported here, injection of 30 or 50 mg silica i.p. increased the severity of the oncogenic effects of the murine sarcoma virus (MSV) and Friend virus (FV) in BALB/c mice. Unlike Herpes simplex and Coxsackie B-3 infections, however, passive transfer of adult macrophages to suckling mice did not protect the latter against MSV. In mice injected with silica, histological evidence of the compensatory proliferation of macrophages suggests that precursors of these cells may act as target cells for the virus and that this may override any immunosuppressive response effected by the silica. In addition, there was a considerable enhancing effect on the erythroproliferative response to both MSV and FV by injection of saline 5 h before the virus, and indeed to FV after only a simple abdominal needle puncture. We attributed this to the lymphopenic immunodepressive effects of stress, and our data may explain previously published findings of augmented oncogenic responses in mice after "normal" serum injections. Newborn BALB/c (FV-1b) mice were susceptible to N-tropic FV, but developed resistance by 29 days of age. Antithymocyte serum (ATS) but not silica injections or adult thymectomy ablated this resistance. C57BL (FV-2r) mice were completely resistant to FV; however, those receiving FV and ATS developed late-onset leukaemia histologically characteristic of that produced by the helper component of the FV complex. Images Fig. PMID:6248095

  12. First report of viral infections that affect argentine honeybees.

    PubMed

    Reynaldi, Francisco José; Sguazza, Guillermo Hernán; Pecoraro, Marcelo Ricardo; Tizzano, Marco Andrés; Galosi, Cecilia Mónica

    2010-12-01

    Honey is one of the most important agricultural products for export in Argentina. In fact, more than 3.5 million beehives and 50 000 beekeepers are related with this production, mainly located in Buenos Aires province. Honeybee mortality is a serious problem that beekeepers in Argentina have had to face during the last 3 years. It is known that the consequence of the complex interactions between environmental and beekeeping parameters added to the effect of different disease agents such as viruses, bacteria, fungi and parasitic mites may result in a sudden collapse of the colony. In addition, multiple viral infections are frequently detected concomitantly in bee colonies. We describe here the preliminary results of a survey of three honeybee-pathogenic viruses, acute bee paralysis viruses (ABPV), chronic bee paralysis viruses (CBPV) and Sacbrood viruses (SBV) detected during a screening of 61 apiaries located in the main honey producer province using a RT-PCR assay. This is the first molecular report of the presence of these viruses in Argentine apiaries.

  13. Some viral and rickettsial infections in Bosnia and Herzegovina

    PubMed Central

    Terzin, A. L.; Gaon, J.

    1956-01-01

    Investigating viral and rickettsial infections in Bosnia and Herzegovina, the authors submitted 115 sera of healthy persons to complement-fixation tests with typhus, Q fever, mumps, rickettsialpox, and psittacosis antigens. The results obtained indicate that the Moslem population tends to show more typhus-positive titres, and at an earlier age, than the non-Moslem. While Moslems under 20 years old tend to develop typhus in epidemic form, an approximately equal number of epidemic and apparently sporadic cases occurs among non-Moslems. On the other hand, Q fever is more frequent, and occurs earlier, in the non-Moslems. An epidemiological explanation of these phenomena is advanced. From the findings on mumps, it is thought possible that this disease tends to be primarily one of children in Moslems but not in non-Moslems. The rickettsialpox titres suggest the presence of an agent or agents antigenically related to Ricksettsia akari, and the psittacosis titres are thought to be caused by contact with organisms of the psittacosis and lymphogranuloma venereum group. PMID:13383366

  14. Analysis of Practical Identifiability of a Viral Infection Model

    PubMed Central

    Nguyen, Van Kinh; Klawonn, Frank; Mikolajczyk, Rafael; Hernandez-Vargas, Esteban A.

    2016-01-01

    Mathematical modelling approaches have granted a significant contribution to life sciences and beyond to understand experimental results. However, incomplete and inadequate assessments in parameter estimation practices hamper the parameter reliability, and consequently the insights that ultimately could arise from a mathematical model. To keep the diligent works in modelling biological systems from being mistrusted, potential sources of error must be acknowledged. Employing a popular mathematical model in viral infection research, existing means and practices in parameter estimation are exemplified. Numerical results show that poor experimental data is a main source that can lead to erroneous parameter estimates despite the use of innovative parameter estimation algorithms. Arbitrary choices of initial conditions as well as data asynchrony distort the parameter estimates but are often overlooked in modelling studies. This work stresses the existence of several sources of error buried in reports of modelling biological systems, voicing the need for assessing the sources of error, consolidating efforts in solving the immediate difficulties, and possibly reconsidering the use of mathematical modelling to quantify experimental data. PMID:28036339

  15. The role of nanotechnology in the treatment of viral infections

    PubMed Central

    Singh, Lavanya; Kruger, Hendrik G.; Maguire, Glenn E.M.; Govender, Thavendran; Parboosing, Raveen

    2017-01-01

    Infectious diseases are the leading cause of mortality worldwide, with viruses in particular making global impact on healthcare and socioeconomic development. In addition, the rapid development of drug resistance to currently available therapies and adverse side effects due to prolonged use is a serious public health concern. The development of novel treatment strategies is therefore required. The interaction of nanostructures with microorganisms is fast-revolutionizing the biomedical field by offering advantages in both diagnostic and therapeutic applications. Nanoparticles offer unique physical properties that have associated benefits for drug delivery. These are predominantly due to the particle size (which affects bioavailability and circulation time), large surface area to volume ratio (enhanced solubility compared to larger particles), tunable surface charge of the particle with the possibility of encapsulation, and large drug payloads that can be accommodated. These properties, which are unlike bulk materials of the same compositions, make nanoparticulate drug delivery systems ideal candidates to explore in order to achieve and/or improve therapeutic effects. This review presents a broad overview of the application of nanosized materials for the treatment of common viral infections. PMID:28748089

  16. Gene Expression Profiles Link Respiratory Viral Infection, Platelet Response to Aspirin, and Acute Myocardial Infarction

    PubMed Central

    Cyr, Derek D.; Lucas, Joseph E.; Zaas, Aimee K.; Woods, Christopher W.; Newby, L. Kristin; Kraus, William E.; Ginsburg, Geoffrey S.

    2015-01-01

    Background Influenza infection is associated with myocardial infarction (MI), suggesting that respiratory viral infection may induce biologic pathways that contribute to MI. We tested the hypotheses that 1) a validated blood gene expression signature of respiratory viral infection (viral GES) was associated with MI and 2) respiratory viral exposure changes levels of a validated platelet gene expression signature (platelet GES) of platelet function in response to aspirin that is associated with MI. Methods A previously defined viral GES was projected into blood RNA data from 594 patients undergoing elective cardiac catheterization and used to classify patients as having evidence of viral infection or not and tested for association with acute MI using logistic regression. A previously defined platelet GES was projected into blood RNA data from 81 healthy subjects before and after exposure to four respiratory viruses: Respiratory Syncytial Virus (RSV) (n=20), Human Rhinovirus (HRV) (n=20), Influenza A virus subtype H1N1 (H1N1) (n=24), Influenza A Virus subtype H3N2 (H3N2) (n=17). We tested for the change in platelet GES with viral exposure using linear mixed-effects regression and by symptom status. Results In the catheterization cohort, 32 patients had evidence of viral infection based upon the viral GES, of which 25% (8/32) had MI versus 12.2% (69/567) among those without evidence of viral infection (OR 2.3; CI [1.03-5.5], p=0.04). In the infection cohorts, only H1N1 exposure increased platelet GES over time (time course p-value = 1e-04). Conclusions A viral GES of non-specific, respiratory viral infection was associated with acute MI; 18% of the top 49 genes in the viral GES are involved with hemostasis and/or platelet aggregation. Separately, H1N1 exposure, but not exposure to other respiratory viruses, increased a platelet GES previously shown to be associated with MI. Together, these results highlight specific genes and pathways that link viral infection

  17. Viral acute lower respiratory infections impair CD8+ T cells through PD-1

    PubMed Central

    Erickson, John J.; Gilchuk, Pavlo; Hastings, Andrew K.; Tollefson, Sharon J.; Johnson, Monika; Downing, Melissa B.; Boyd, Kelli L.; Johnson, Joyce E.; Kim, Annette S.; Joyce, Sebastian; Williams, John V.

    2012-01-01

    Viruses are leading causes of severe acute lower respiratory infections (LRIs). These infections evoke incomplete immunity, as individuals can be repeatedly reinfected throughout life. We report that acute viral LRI causes rapid pulmonary CD8+ cytotoxic T lymphocyte (TCD8) functional impairment via programmed death–1/programmed death ligand–1 (PD-1/PD-L1) signaling, a pathway previously associated with prolonged antigenic stimulation during chronic infections and cancer. PD-1–mediated TCD8 impairment occurred acutely in mice following infection with human metapneumovirus or influenza virus. Viral antigen was sufficient for PD-1 upregulation, but induction of PD-L1 was required for impairment. During secondary viral infection or epitope-only challenge, memory TCD8 rapidly reexpressed PD-1 and exhibited severe functional impairment. Inhibition of PD-1 signaling using monoclonal antibody blockade prevented TCD8 impairment, reduced viral titers during primary infection, and enhanced protection of immunized mice against challenge infection. Additionally, PD-1 and PD-L1 were upregulated in the lungs of patients with 2009 H1N1 influenza virus, respiratory syncytial virus, or parainfluenza virus infection. These results indicate that PD-1 mediates TCD8 functional impairment during acute viral infection and may contribute to recurrent viral LRIs. Therefore, the PD-1/PD-L1 pathway may represent a therapeutic target in the treatment of respiratory viruses. PMID:22797302

  18. Viral Load Drives Disease in Humans Experimentally Infected with Respiratory Syncytial Virus

    PubMed Central

    DeVincenzo, John P.; Wilkinson, Tom; Vaishnaw, Akshay; Cehelsky, Jeff; Meyers, Rachel; Nochur, Saraswathy; Harrison, Lisa; Meeking, Patricia; Mann, Alex; Moane, Elizabeth; Oxford, John; Pareek, Rajat; Moore, Ryves; Walsh, Ed; Studholme, Robert; Dorsett, Preston; Alvarez, Rene; Lambkin-Williams, Robert

    2010-01-01

    Rationale: Respiratory syncytial virus (RSV) is the leading cause of childhood lower respiratory infection, yet viable therapies are lacking. Two major challenges have stalled antiviral development: ethical difficulties in performing pediatric proof-of-concept studies and the prevailing concept that the disease is immune-mediated rather than being driven by viral load. Objectives: The development of a human experimental wild-type RSV infection model to address these challenges. Methods: Healthy volunteers (n = 35), in five cohorts, received increasing quantities (3.0–5.4 log plaque-forming units/person) of wild-type RSV-A intranasally. Measurements and Main Results: Overall, 77% of volunteers consistently shed virus. Infection rate, viral loads, disease severity, and safety were similar between cohorts and were unrelated to quantity of RSV received. Symptoms began near the time of initial viral detection, peaked in severity near when viral load peaked, and subsided as viral loads (measured by real-time polymerase chain reaction) slowly declined. Viral loads correlated significantly with intranasal proinflammatory cytokine concentrations (IL-6 and IL-8). Increased viral load correlated consistently with increases in multiple different disease measurements (symptoms, physical examination, and amount of nasal mucus). Conclusions: Viral load appears to drive disease manifestations in humans with RSV infection. The observed parallel viral and disease kinetics support a potential clinical benefit of RSV antivirals. This reproducible model facilitates the development of future RSV therapeutics. PMID:20622030

  19. Inferring Viral Dynamics in Chronically HCV Infected Patients from the Spatial Distribution of Infected Hepatocytes

    SciTech Connect

    Graw, Frederik; Balagopal, Ashwin; Kandathil, Abraham J.; Ray, Stuart C.; Thomas, David L.; Ribeiro, Ruy M.; Perelson, Alan S.; Yates, Andrew J.

    2014-11-13

    Chronic liver infection by hepatitis C virus (HCV) is a major public health concern. Despite partly successful treatment options, several aspects of intrahepatic HCV infection dynamics are still poorly understood, including the preferred mode of viral propagation, as well as the proportion of infected hepatocytes. Answers to these questions have important implications for the development of therapeutic interventions. In this study, we present methods to analyze the spatial distribution of infected hepatocytes obtained by single cell laser capture microdissection from liver biopsy samples of patients chronically infected with HCV. By characterizing the internal structure of clusters of infected cells, we are able to evaluate hypotheses about intrahepatic infection dynamics. We found that individual clusters on biopsy samples range in size from 4-50 infected cells. In addition, the HCV RNA content in a cluster declines from the cell that presumably founded the cluster to cells at the maximal cluster extension. These observations support the idea that HCV infection in the liver is seeded randomly (e.g. from the blood) and then spreads locally. Assuming that the amount of intracellular HCV RNA is a proxy for how long a cell has been infected, we estimate based on models of intracellular HCV RNA replication and accumulation that cells in clusters have been infected on average for less than a week. Further, we do not find a relationship between the cluster size and the estimated cluster expansion time. Lastly, our method represents a novel approach to make inferences about infection dynamics in solid tissues from static spatial data.

  20. Inferring Viral Dynamics in Chronically HCV Infected Patients from the Spatial Distribution of Infected Hepatocytes

    DOE PAGES

    Graw, Frederik; Balagopal, Ashwin; Kandathil, Abraham J.; ...

    2014-11-13

    Chronic liver infection by hepatitis C virus (HCV) is a major public health concern. Despite partly successful treatment options, several aspects of intrahepatic HCV infection dynamics are still poorly understood, including the preferred mode of viral propagation, as well as the proportion of infected hepatocytes. Answers to these questions have important implications for the development of therapeutic interventions. In this study, we present methods to analyze the spatial distribution of infected hepatocytes obtained by single cell laser capture microdissection from liver biopsy samples of patients chronically infected with HCV. By characterizing the internal structure of clusters of infected cells, wemore » are able to evaluate hypotheses about intrahepatic infection dynamics. We found that individual clusters on biopsy samples range in size from 4-50 infected cells. In addition, the HCV RNA content in a cluster declines from the cell that presumably founded the cluster to cells at the maximal cluster extension. These observations support the idea that HCV infection in the liver is seeded randomly (e.g. from the blood) and then spreads locally. Assuming that the amount of intracellular HCV RNA is a proxy for how long a cell has been infected, we estimate based on models of intracellular HCV RNA replication and accumulation that cells in clusters have been infected on average for less than a week. Further, we do not find a relationship between the cluster size and the estimated cluster expansion time. Lastly, our method represents a novel approach to make inferences about infection dynamics in solid tissues from static spatial data.« less

  1. Synaptic transmission and the susceptibility of HIV infection to anti-viral drugs

    NASA Astrophysics Data System (ADS)

    Komarova, Natalia L.; Levy, David N.; Wodarz, Dominik

    2013-07-01

    Cell-to-cell viral transmission via virological synapses has been argued to reduce susceptibility of the virus population to anti-viral drugs through multiple infection of cells, contributing to low-level viral persistence during therapy. Using a mathematical framework, we examine the role of synaptic transmission in treatment susceptibility. A key factor is the relative probability of individual virions to infect a cell during free-virus and synaptic transmission, a currently unknown quantity. If this infection probability is higher for free-virus transmission, then treatment susceptibility is lowest if one virus is transferred per synapse, and multiple infection of cells increases susceptibility. In the opposite case, treatment susceptibility is minimized for an intermediate number of virions transferred per synapse. Hence, multiple infection via synapses does not simply lower treatment susceptibility. Without further experimental investigations, one cannot conclude that synaptic transmission provides an additional mechanism for the virus to persist at low levels during anti-viral therapy.

  2. Peroxynitrite inhibition of Coxsackievirus infection by prevention of viral RNA entry

    PubMed Central

    Padalko, Elizaveta; Ohnishi, Tomokazu; Matsushita, Kenji; Sun, Henry; Fox-Talbot, Karen; Bao, Clare; Baldwin, William M.; Lowenstein, Charles J.

    2004-01-01

    Although peroxynitrite is harmful to the host, the beneficial effects of peroxynitrite are less well understood. We explored the role of peroxynitrite in the host immune response to Coxsackievirus infection. Peroxynitrite inhibits viral replication in vitro, in part by inhibiting viral RNA entry into the host cell. Nitrotyrosine, a marker for peroxynitrite production, is colocalized with viral antigens in the hearts of infected mice but not control mice. Nitrotyrosine coprecipitates with the viral polypeptide VP1 as well. Guanidinoethyl disulfide, a scavenger of peroxynitrite, blocks peroxynitrite inhibition of viral replication in vitro and permits an increase in viral replication in vivo. These data suggest that peroxynitrite is an endogenous effector of the immune response to viruses. PMID:15286280

  3. p53 Activation following Rift Valley Fever Virus Infection Contributes to Cell Death and Viral Production

    PubMed Central

    Lundberg, Lindsay; Shafagati, Nazly; Schoonmaker, Annalise; Narayanan, Aarthi; Popova, Taissia; Panthier, Jean Jacques; Kashanchi, Fatah; Bailey, Charles; Kehn-Hall, Kylene

    2012-01-01

    Rift Valley fever virus (RVFV) is an emerging viral zoonosis that is responsible for devastating outbreaks among livestock and is capable of causing potentially fatal disease in humans. Studies have shown that upon infection, certain viruses have the capability of utilizing particular cellular signaling pathways to propagate viral infection. Activation of p53 is important for the DNA damage signaling cascade, initiation of apoptosis, cell cycle arrest and transcriptional regulation of multiple genes. The current study focuses on the role of p53 signaling in RVFV infection and viral replication. These results show an up-regulation of p53 phosphorylation at several serine sites after RVFV MP-12 infection that is highly dependent on the viral protein NSs. qRT-PCR data showed a transcriptional up-regulation of several p53 targeted genes involved in cell cycle and apoptosis regulation following RVFV infection. Cell viability assays demonstrate that loss of p53 results in less RVFV induced cell death. Furthermore, decreased viral titers in p53 null cells indicate that RVFV utilizes p53 to enhance viral production. Collectively, these experiments indicate that the p53 signaling pathway is utilized during RVFV infection to induce cell death and increase viral production. PMID:22574148

  4. [Prevalence and risk factors of respiratory viral infection in acute exacerbation of chronic obstructive pulmonary disease].

    PubMed

    Du, X B; Ma, X; Gao, Y; Wen, L F; Li, J; Wang, Z Z; Liu, S

    2017-04-12

    Objective: To study the prevalence of respiratory viral infection in chronic obstructive pulmonary disease(COPD) exacerbations and to find the factors associated with susceptibility to viral infections. Methods: Eighty patients with exacerbations of COPD and 50 stable COPD patients were recruited. Nasopharyngeal swabs were tested for a range of 18 different respiratory viruses using PCR. Results: Among the COPD exacerbations, viral infection was detected in 18 episodes (22.5%) . The most common virus was rhinovirus (33.3%), followed by coronavirus(27.8%), parainfluenza(22.2%), metapneumovirus(11.1%) and influenza virus B(5.6%). The prevalence of viral infection was 8% in the stable COPD patients. In multivariate regression analysis fever was found to be significantly associated with viral infections in COPD exacerbations (Odds ratio 4.99, 95%CI 1.51-16.48, P=0.008). Conclusion: Viral respiratory pathogens were more often detected in respiratory specimens from hospitalized patients with AECOPD than those with stable COPD. Rhinovirus was the most common infecting agent identified. The symptom of fever was associated with viral detection.

  5. p53 Activation following Rift Valley fever virus infection contributes to cell death and viral production.

    PubMed

    Austin, Dana; Baer, Alan; Lundberg, Lindsay; Shafagati, Nazly; Schoonmaker, Annalise; Narayanan, Aarthi; Popova, Taissia; Panthier, Jean Jacques; Kashanchi, Fatah; Bailey, Charles; Kehn-Hall, Kylene

    2012-01-01

    Rift Valley fever virus (RVFV) is an emerging viral zoonosis that is responsible for devastating outbreaks among livestock and is capable of causing potentially fatal disease in humans. Studies have shown that upon infection, certain viruses have the capability of utilizing particular cellular signaling pathways to propagate viral infection. Activation of p53 is important for the DNA damage signaling cascade, initiation of apoptosis, cell cycle arrest and transcriptional regulation of multiple genes. The current study focuses on the role of p53 signaling in RVFV infection and viral replication. These results show an up-regulation of p53 phosphorylation at several serine sites after RVFV MP-12 infection that is highly dependent on the viral protein NSs. qRT-PCR data showed a transcriptional up-regulation of several p53 targeted genes involved in cell cycle and apoptosis regulation following RVFV infection. Cell viability assays demonstrate that loss of p53 results in less RVFV induced cell death. Furthermore, decreased viral titers in p53 null cells indicate that RVFV utilizes p53 to enhance viral production. Collectively, these experiments indicate that the p53 signaling pathway is utilized during RVFV infection to induce cell death and increase viral production.

  6. Effect of Acyclovir on Viral Protein Synthesis in Cells Infected with Herpes Simplex Virus Type 1

    PubMed Central

    Furman, Phillip A.; McGuirt, Paul V.

    1983-01-01

    The effect of the antiviral agent 9-(2-hydroxyethoxymethyl)guanine (acyclovir) on herpes simplex virus type 1 protein synthesis during virus replication was examined. Treatment of infected cells with acyclovir markedly affected the amounts of the four major glycosylated and certain non-glycosylated viral polypeptides synthesized; other viral polypeptides were made in normal amounts. The reduced amount of late protein synthesis was most likely due to the inhibition of progeny viral DNA synthesis by acyclovir. Images PMID:6301368

  7. Rabies Virus Infection Induces the Formation of Stress Granules Closely Connected to the Viral Factories

    PubMed Central

    Nikolic, Jovan; Civas, Ahmet; Lagaudrière-Gesbert, Cécile; Blondel, Danielle

    2016-01-01

    Stress granules (SGs) are membrane-less dynamic structures consisting of mRNA and protein aggregates that form rapidly in response to a wide range of environmental cellular stresses and viral infections. They act as storage sites for translationally silenced mRNAs under stress conditions. During viral infection, SG formation results in the modulation of innate antiviral immune responses, and several viruses have the ability to either promote or prevent SG assembly. Here, we show that rabies virus (RABV) induces SG formation in infected cells, as revealed by the detection of SG-marker proteins Ras GTPase-activating protein-binding protein 1 (G3BP1), T-cell intracellular antigen 1 (TIA-1) and poly(A)-binding protein (PABP) in the RNA granules formed during viral infection. As shown by live cell imaging, RABV-induced SGs are highly dynamic structures that increase in number, grow in size by fusion events, and undergo assembly/disassembly cycles. Some SGs localize in close proximity to cytoplasmic viral factories, known as Negri bodies (NBs). Three dimensional reconstructions reveal that both structures remain distinct even when they are in close contact. In addition, viral mRNAs synthesized in NBs accumulate in the SGs during viral infection, revealing material exchange between both compartments. Although RABV-induced SG formation is not affected in MEFs lacking TIA-1, TIA-1 depletion promotes viral translation which results in an increase of viral replication indicating that TIA-1 has an antiviral effect. Inhibition of PKR expression significantly prevents RABV-SG formation and favors viral replication by increasing viral translation. This is correlated with a drastic inhibition of IFN-B gene expression indicating that SGs likely mediate an antiviral response which is however not sufficient to fully counteract RABV infection. PMID:27749929

  8. Prevalence and incidence of bloodborne viral infections among Danish prisoners.

    PubMed

    Christensen, P B; Krarup, H B; Niesters, H G; Norder, H; Georgsen, J

    2000-01-01

    In order to determine the prevalence and incidence of bloodborne viral infections among prisoners, we conducted a prospective study in a Danish medium security prison for males. The prisoners were offered an interview and blood test for hepatitis and human immunodeficiency virus HIV at inclusion as well as at release from prison or end of study. Of 403 prisoners available 325 (79%) participated in the initial survey and for 142 (44%) a follow-up test was available. 43% (140/325) of the participants were injecting drug users (IDUs) of whom 64% were positive for hepatitis B (HBV) and 87% for hepatitis C (HCV) markers. No cases of HIV or human T lymphotropic virus (HTLV) were found. 32% of all prisoners could transmit HBV and/or HCV by blood contact. 70% of IDUs had shared injecting equipment, and 60% had injected inside prison. Only 2% of IDUs were vaccinated against HBV. Duration of injecting drug use, numbers of imprisonments, and injecting in prison were independently and positively associated with the presence of HBV antibodies among IDUs by logistic regression analysis. The HBV incidence was 16/100 PY (95% CI: 2-56/100 PY) and the HCV incidence 25/100 PY (1-140) among injecting drug users (IDUs). We conclude that IDUs in prison have an incidence of hepatitis B and C 100 times higher than reported in the general Danish population. They should be vaccinated against hepatitis B and new initiatives to stop sharing of injecting equipment in and outside prison is urgently needed.

  9. Immune and Viral Correlates of “Secondary Viral Control” after Treatment Interruption in Chronically HIV-1 Infected Patients

    PubMed Central

    Van Gulck, Ellen; Bracke, Lotte; Heyndrickx, Leo; Coppens, Sandra; Atkinson, Derek; Merlin, Céline; Pasternak, Alexander; Florence, Eric; Vanham, Guido

    2012-01-01

    Upon interruption of antiretroviral therapy, HIV-infected patients usually show viral load rebound to pre-treatment levels. Four patients, hereafter referred to as secondary controllers (SC), were identified who initiated therapy during chronic infection and, after stopping treatment, could control virus replication at undetectable levels for more than six months. In the present study we set out to unravel possible viral and immune parameters or mechanisms of this phenomenon by comparing secondary controllers with elite controllers and non-controllers, including patients under HAART. As candidate correlates of protection, virus growth kinetics, levels of intracellular viral markers, several aspects of HIV-specific CD4+ and CD8+ T cell function and HIV neutralizing antibodies were investigated. As expected all intracellular viral markers were lower in aviremic as compared to viremic subjects, but in addition both elite and secondary controllers had lower levels of viral unspliced RNA in PBMC as compared to patients on HAART. Ex vivo cultivation of the virus from CD4+ T cells of SC consistently failed in one patient and showed delayed kinetics in the three others. Formal in vitro replication studies of these three viruses showed low to absent growth in two cases and a virus with normal fitness in the third case. T cell responses toward HIV peptides, evaluated in IFN-γ ELISPOT, revealed no significant differences in breadth, magnitude or avidity between SC and all other patient groups. Neither was there a difference in polyfunctionality of CD4+ or CD8+ T cells, as evaluated with intracellular cytokine staining. However, secondary and elite controllers showed higher proliferative responses to Gag and Pol peptides. SC also showed the highest level of autologous neutralizing antibodies. These data suggest that higher T cell proliferative responses and lower replication kinetics might be instrumental in secondary viral control in the absence of treatment. PMID:22666392

  10. Epidemiology and prevention of pediatric viral respiratory infections in health-care institutions.

    PubMed Central

    Goldmann, D. A.

    2001-01-01

    Nosocomial viral respiratory infections cause considerable illness and death on pediatric wards. Common causes of these infections include respiratory syncytial virus and influenza. Although primarily a community pathogen, rhinovirus also occasionally results in hospitalization and serious sequelae. This article reviews effective infection control interventions for these three pathogens, as well as ongoing controversies. PMID:11294717

  11. Experimental infection of pregnant goats with bovine viral diarrhea virus (BVDV)1 or 2

    USDA-ARS?s Scientific Manuscript database

    Infections with bovine viral diarrhea virus (BVDV) of the genus pestivirus, family Flaviviridae, are not limited to cattle but occur in various artiodactyls. Persistently infected (PI) cattle are the main source of BVDV. Persistent infections also occur in heterologous hosts such as sheep and deer. ...

  12. Peripheral immunophenotype and viral promoter variants during the asymptomatic phase of feline immunodeficiency virus infection

    PubMed Central

    Murphy, B.; Hillman, C.; McDonnel, S.

    2014-01-01

    Feline immunodeficiency virus (FIV)-infected cats enter a clinically asymptomatic phase during chronic infection. Despite the lack of overt clinical disease, the asymptomatic phase is characterized by persistent immunologic impairment. In the peripheral blood obtained from cats experimentally infected with FIV-C for approximately 5 years, we identified a persistent inversion of the CD4/CD8 ratio. We cloned and sequenced the FIV-C long terminal repeat containing the viral promoter from cells infected with the inoculating virus and from in vivo-derived peripheral blood mononuclear cells and CD4 T cells isolated at multiple time points throughout the asymptomatic phase. Relative to the inoculating virus, viral sequences amplified from cells isolated from all of the infected animals demonstrated multiple single nucleotide mutations and a short deletion within the viral U3, R and U5 regions. A transcriptionally inactivating proviral mutation in the U3 promoter AP-1 site was identified at multiple time points from all of the infected animals but not within cell-associated viral RNA. In contrast, no mutations were identified within the sequence of the viral dUTPase gene amplified from PBMC isolated at approximately 5 years post-infection relative to the inoculating sequence. The possible implications of these mutations to viral pathogenesis are discussed. PMID:24291288

  13. HIV RNA level in early infection is predicted by viral load in the transmission source

    PubMed Central

    Hecht, Frederick M.; Hartogensis, Wendy; Bragg, Larry; Bacchetti, Peter; Atchison, Robert; Grant, Robert; Barbour, Jason; Deeks, Steven G.

    2010-01-01

    Objective HIV-1 viral load in early infection predicts the risk of subsequent disease progression but the factors responsible for the differences between individuals in viral load during this period have not been fully identified. We sought to determine the relationship between HIV-1 RNA levels in the source partner and recently infected recipient partners within transmission pairs. Methods We recruited donor partners of persons who presented with acute or recent (< 6 months) HIV infection. Transmission was confirmed by phyologenetic comparison of virus sequence in the donor and recipient partners. We compared viral load in the donor partner and the recipient in the first 6 months of HIV infection. Results We identified 24 transmission pairs. The median estimated time from infection to evaluation in acutely/recently infected recipient individuals was 72 days. The viral load in the donor was closely associated with viral load at presentation in the recipient case (r=0.55, P=0.006). Conclusion The strong correlation between HIV-1 RNA levels within HIV transmission pairs indicates that virus characteristics are an important determinant of viral load in early HIV infection. PMID:20168202

  14. Temporal effect of HLA-B*57 on viral control during primary HIV-1 infection

    PubMed Central

    2013-01-01

    Background HLA-B alleles are associated with viral control in chronic HIV-1 infection, however, their role in primary HIV-1 disease is unclear. This study sought to determine the role of HLA-B alleles in viral control during the acute phase of HIV-1 infection and establishment of the early viral load set point (VLSP). Findings Individuals identified during primary HIV-1 infection were HLA class I typed and followed longitudinally. Associations between HLA-B alleles and HIV-1 viral replication during acute infection and VLSP were analyzed in untreated subjects. The results showed that neither HLA-B*57 nor HLA-B*27 were significantly associated with viral control during acute HIV-1 infection (Fiebig stage I-IV, n=171). HLA-B*57 was however significantly associated with a subsequent lower VLSP (p<0.001, n=135) with nearly 1 log10 less median viral load. Analysis of a known polymorphism at position 97 of HLA-B showed significant associations with both lower initial viral load (p<0.01) and lower VLSP (p<0.05). However, this association was dependent on different amino acids at this position for each endpoint. Conclusions The effect of HLA-B*57 on viral control is more pronounced during the later stages of primary HIV-1 infection, which suggests the underlying mechanism of control occurs at a critical period in the first several months after HIV-1 acquisition. The risk profile of polymorphisms at position 97 of HLA-B are more broadly associated with HIV-1 viral load during primary infection and may serve as a focal point in further studies of HLA-B function. PMID:24245727

  15. Stochastic theory of early viral infection: continuous versus burst production of virions.

    PubMed

    Pearson, John E; Krapivsky, Paul; Perelson, Alan S

    2011-02-03

    Viral production from infected cells can occur continuously or in a burst that generally kills the cell. For HIV infection, both modes of production have been suggested. Standard viral dynamic models formulated as sets of ordinary differential equations can not distinguish between these two modes of viral production, as the predicted dynamics is identical as long as infected cells produce the same total number of virions over their lifespan. Here we show that in stochastic models of viral infection the two modes of viral production yield different early term dynamics. Further, we analytically determine the probability that infections initiated with any number of virions and infected cells reach extinction, the state when both the population of virions and infected cells vanish, and show this too has different solutions for continuous and burst production. We also compute the distributions of times to establish infection as well as the distribution of times to extinction starting from both a single virion as well as from a single infected cell for both modes of virion production.

  16. Follicular CXCR5- expressing CD8(+) T cells curtail chronic viral infection.

    PubMed

    He, Ran; Hou, Shiyue; Liu, Cheng; Zhang, Anli; Bai, Qiang; Han, Miao; Yang, Yu; Wei, Gang; Shen, Ting; Yang, Xinxin; Xu, Lifan; Chen, Xiangyu; Hao, Yaxing; Wang, Pengcheng; Zhu, Chuhong; Ou, Juanjuan; Liang, Houjie; Ni, Ting; Zhang, Xiaoyan; Zhou, Xinyuan; Deng, Kai; Chen, Yaokai; Luo, Yadong; Xu, Jianqing; Qi, Hai; Wu, Yuzhang; Ye, Lilin

    2016-08-02

    During chronic viral infection, virus-specific CD8(+) T cells become exhausted, exhibit poor effector function and lose memory potential. However, exhausted CD8(+) T cells can still contain viral replication in chronic infections, although the mechanism of this containment is largely unknown. Here we show that a subset of exhausted CD8(+) T cells expressing the chemokine receptor CXCR5 has a critical role in the control of viral replication in mice that were chronically infected with lymphocytic choriomeningitis virus (LCMV). These CXCR5(+) CD8(+) T cells were able to migrate into B-cell follicles, expressed lower levels of inhibitory receptors and exhibited more potent cytotoxicity than the CXCR5(-) [corrected] subset. Furthermore, we identified the Id2-E2A signalling axis as an important regulator of the generation of this subset. In patients with HIV, we also identified a virus-specific CXCR5(+) CD8(+) T-cell subset, and its number was inversely correlated with viral load. The CXCR5(+) subset showed greater therapeutic potential than the CXCR5(-) [corrected] subset when adoptively transferred to chronically infected mice, and exhibited synergistic reduction of viral load when combined with anti-PD-L1 treatment. This study defines a unique subset of exhausted CD8(+) T cells that has a pivotal role in the control of viral replication during chronic viral infection.

  17. Alpha-Synuclein Expression Restricts RNA Viral Infections in the Brain

    PubMed Central

    Beatman, Erica L.; Massey, Aaron; Shives, Katherine D.; Burrack, Kristina S.; Chamanian, Mastooreh; Morrison, Thomas E.

    2015-01-01

    ABSTRACT We have discovered that native, neuronal expression of alpha-synuclein (Asyn) inhibits viral infection, injury, and disease in the central nervous system (CNS). Enveloped RNA viruses, such as West Nile virus (WNV), invade the CNS and cause encephalitis, yet little is known about the innate neuron-specific inhibitors of viral infections in the CNS. Following WNV infection of primary neurons, we found that Asyn protein expression is increased. The infectious titer of WNV and Venezuelan equine encephalitis virus (VEEV) TC83 in the brains of Asyn-knockout mice exhibited a mean increase of 104.5 infectious viral particles compared to the titers in wild-type and heterozygote littermates. Asyn-knockout mice also exhibited significantly increased virus-induced mortality compared to Asyn heterozygote or homozygote control mice. Virus-induced Asyn localized to perinuclear, neuronal regions expressing viral envelope protein and the endoplasmic reticulum (ER)-associated trafficking protein Rab1. In Asyn-knockout primary neuronal cultures, the levels of expression of ER signaling pathways, known to support WNV replication, were significantly elevated before and during viral infection compared to those in Asyn-expressing primary neuronal cultures. We propose a model in which virus-induced Asyn localizes to ER-derived membranes, modulates virus-induced ER stress signaling, and inhibits viral replication, growth, and injury in the CNS. These data provide a novel and important functional role for the expression of native alpha-synuclein, a protein that is closely associated with the development of Parkinson's disease. IMPORTANCE Neuroinvasive viruses such as West Nile virus are able to infect neurons and cause severe disease, such as encephalitis, or infection of brain tissue. Following viral infection in the central nervous system, only select neurons are infected, implying that neurons exhibit innate resistance to viral infections. We discovered that native neuronal

  18. Viral bacterial co-infection of the respiratory tract during early childhood.

    PubMed

    Brealey, Jaelle C; Sly, Peter D; Young, Paul R; Chappell, Keith J

    2015-05-01

    Acute respiratory infection (ARI) is an important cause of morbidity in children. Mixed aetiology is frequent, with pathogenic viruses and bacteria co-detected in respiratory secretions. However, the clinical significance of these viral/bacterial co-infections has long been a controversial topic. While severe bacterial pneumonia following influenza infection has been well described, associations are less clear among infections caused by viruses that are more common in young children, such as respiratory syncytial virus. Although assessing the overall contribution of bacteria to disease severity is complicated by the presence of many confounding factors in clinical studies, understanding the role of viral/bacterial co-infections in defining the outcome of paediatric ARI will potentially reveal novel treatment and prevention strategies, improving patient outcomes. This review summarizes current evidence for the clinical significance of respiratory viral/bacterial co-infections in young children, discusses possible mechanisms of cooperative interaction between these pathogens and highlights areas that require further investigation.

  19. Impact of cell regeneration in human respiratory tract on simultaneous viral infections

    NASA Astrophysics Data System (ADS)

    Pinky, Lubna Jahan Rashid; Dobrovolny, Hana

    2015-03-01

    Studies have found that ~ 40% of patients hospitalized with influenza-like illness are infected with at least two different viruses. In these longer infections, we need to consider the role of cell regeneration. Several mathematical models have been used to describe cell regeneration in infection models, though the effect of model choice on the predicted time course of simultaneous viral infections is not clear. We investigate a series of mathematical models of cell regeneration during simultaneous respiratory virus infections to determine the effect of cell regeneration on infection dynamics. We perform a nonlinear stability analysis for each model. The analysis suggests that coexistence of two viral species is not possible for any form of regeneration. We find that chronic illness is possible, but with only one viral species.

  20. Cleavage of Grb2-Associated Binding Protein 2 by Viral Proteinase 2A during Coxsackievirus Infection

    PubMed Central

    Deng, Haoyu; Fung, Gabriel; Qiu, Ye; Wang, Chen; Zhang, Jingchun; Jin, Zheng-Gen; Luo, Honglin

    2017-01-01

    Coxsackievirus type B3 (CV-B3), an enterovirus associated with the pathogenesis of several human diseases, subverts, or employs the host intracellular signaling pathways to support effective viral infection. We have previously demonstrated that Grb2-associated binding protein 1 (GAB1), a signaling adaptor protein that serves as a platform for intracellular signaling assembly and transduction, is cleaved upon CV-B3 infection, resulting in a gain-of-pro-viral-function via the modification of GAB1-mediated ERK1/2 pathway. GAB2 is a mammalian homolog of GAB1. In this study, we aim to address whether GAB2 plays a synergistic role with GAB1 in the regulation of CV-B3 replication. Here, we reported that GAB2 is also a target of CV-B3-encoded viral proteinase. We showed that GAB2 is cleaved at G238 during CV-B3 infection by viral proteinase 2A, generating two cleaved fragments of GAB2-N1−237 and GAB2-C238−676. Moreover, knockdown of GAB2 significantly inhibits the synthesis of viral protein and subsequent viral progeny production, accompanied by reduced levels of phosphorylated p38, suggesting a pro-viral function for GAB2 linked to p38 activation. Finally, we examined whether the cleavage of GAB2 can promote viral replication as observed for GAB1 cleavage. We showed that expression of neither GAB2-N1−237 nor GAB2-C238−676 results in enhanced viral infectivity, indicating a loss-of-function, rather than a gain-of-function of GAB2 cleavage in mediating virus replication. Taken together, our findings in this study suggest a novel host defense machinery through which CV-B3 infection is limited by the cleavage of a pro-viral protein. PMID:28361043

  1. Global stability of a multiple delayed viral infection model with general incidence rate and an application to HIV infection.

    PubMed

    Ji, Yu

    2015-06-01

    In this paper, the dynamical behavior of a viral infection model with general incidence rate and two time delays is studied. By using the Lyapunov functional and LaSalle invariance principle, the global stabilities of the infection-free equilibrium and the endemic equilibrium are obtained. We obtain a threshold of the global stability for the uninfected equilibrium, which means the disease will be under control eventually. These results can be applied to a variety of viral infections of disease that would make it possible to devise optimal treatment strategies. Numerical simulations with application to HIV infection are given to verify the analytical results.

  2. Who Regulates Whom? An Overview of RNA Granules and Viral Infections.

    PubMed

    Poblete-Durán, Natalia; Prades-Pérez, Yara; Vera-Otarola, Jorge; Soto-Rifo, Ricardo; Valiente-Echeverría, Fernando

    2016-06-28

    After viral infection, host cells respond by mounting an anti-viral stress response in order to create a hostile atmosphere for viral replication, leading to the shut-off of mRNA translation (protein synthesis) and the assembly of RNA granules. Two of these RNA granules have been well characterized in yeast and mammalian cells, stress granules (SGs), which are translationally silent sites of RNA triage and processing bodies (PBs), which are involved in mRNA degradation. This review discusses the role of these RNA granules in the evasion of anti-viral stress responses through virus-induced remodeling of cellular ribonucleoproteins (RNPs).

  3. How does viral DNA find the nucleus of an infected cell?

    PubMed Central

    Widulle, Herbert

    2012-01-01

    If all locations of a living cell would have the same chemical potential, most viral infections of a cell should be abortive, even after the a penetration of the cell wall by the viral DNA-polymer or viral RNA-polymer occurred. This is obviously not the case. Therefore, there must be a mechanism which transports a viral DNA-polymer from the cell wall to the nucleus and not to any other location. A possible mechanism is proposed which is in accordance with biophysical chemistry. The presented description of the mechanism uses non equilibrium thermodynamics to find a simple solution for the problem. PMID:22558035

  4. Who Regulates Whom? An Overview of RNA Granules and Viral Infections

    PubMed Central

    Poblete-Durán, Natalia; Prades-Pérez, Yara; Vera-Otarola, Jorge; Soto-Rifo, Ricardo; Valiente-Echeverría, Fernando

    2016-01-01

    After viral infection, host cells respond by mounting an anti-viral stress response in order to create a hostile atmosphere for viral replication, leading to the shut-off of mRNA translation (protein synthesis) and the assembly of RNA granules. Two of these RNA granules have been well characterized in yeast and mammalian cells, stress granules (SGs), which are translationally silent sites of RNA triage and processing bodies (PBs), which are involved in mRNA degradation. This review discusses the role of these RNA granules in the evasion of anti-viral stress responses through virus-induced remodeling of cellular ribonucleoproteins (RNPs). PMID:27367717

  5. Viral infections in workers in hospital and research laboratory settings: a comparative review of infection modes and respective biosafety aspects.

    PubMed

    Pedrosa, Pedro B S; Cardoso, Telma A O

    2011-06-01

    To compare modes and sources of infection and clinical and biosafety aspects of accidental viral infections in hospital workers and research laboratory staff reported in scientific articles. PubMed, Google Scholar, ISI Web of Knowledge, Scirus, and Scielo were searched (to December 2008) for reports of accidental viral infections, written in English, Portuguese, Spanish, or German; the authors' personal file of scientific articles and references from the articles retrieved in the initial search were also used. Systematic review was carried out with inclusion criteria of presence of accidental viral infection's cases information, and exclusion criteria of absence of information about the viral etiology, and at least probable mode of infection. One hundred and forty-one scientific articles were obtained, 66 of which were included in the analysis. For arboviruses, 84% of the laboratory infections had aerosol as the source; for alphaviruses alone, aerosol exposure accounted for 94% of accidental infections. Of laboratory arboviral infections, 15.7% were acquired percutaneously, whereas 41.6% of hospital infections were percutaneous. For airborne viruses, 81% of the infections occurred in laboratories, with hantavirus the leading causative agent. Aerosol inhalation was implicated in 96% of lymphocytic choriomeningitis virus infections, 99% of hantavirus infections, and 50% of coxsackievirus infections, but infective droplet inhalation was the leading mode of infection for severe acute respiratory syndrome coronavirus and the mucocutaneous mode of infection was involved in the case of infection with influenza B. For blood-borne viruses, 92% of infections occurred in hospitals and 93% of these had percutaneous mode of infection, while among laboratory infections 77% were due to infective aerosol inhalation. Among blood-borne virus infections there were six cases of particular note: three cases of acute hepatitis following hepatitis C virus infection with a short period of

  6. Viral Load and CD4+ T-Cell Dynamics in Primary HIV-1 Subtype C Infection

    PubMed Central

    Novitsky, Vladimir; Woldegabriel, Elias; Kebaabetswe, Lemme; Rossenkhan, Raabya; Mlotshwa, Busisiwe; Bonney, Caitlin; Finucane, Mariel; Musonda, Rosemary; Moyo, Sikhulile; Wester, Carolyn; van Widenfelt, Erik; Makhema, Joseph; Lagakos, Stephen; Essex, M.

    2009-01-01

    Background Most knowledge of primary HIV-1 infection is based on subtype B studies, whereas the evolution of viral parameters in the early phase of HIV-1 subtype C infection is not well characterized. Methods The kinetics of viral RNA, proviral DNA, CD4+ T-cell count, and subsets of CD4+ T cells expressing CCR5 or CXCR4 were characterized in 8 acute and 62 recent subtype C infections over the first year postseroconversion. Results The viral RNA peak was 6.25 ± 0.92 log10 copies per milliliter. After seroconversion, heterogeneity among acute cases was evident by patterns of change in viral load and CD4+ T-cell count over time. The patterns were supported by the rate of viral RNA decline from peak (P = 0.022), viral RNA means (P = 0.005), CD4 levels (P <0.001), and CD4 decline to 350 (P = 0.011) or 200 (P = 0.046). Proviral DNA had no apparent peak and its mean was 2.59 ± 0.69 log10 per 106 peripheral blood mononuclear cell. In recent infections, viral RNA set point was 4.00 ± 0.97 log10 and viral RNA correlated inversely with CD4+ T cells (P <0.001) and directly with proviral DNA (P <0.001). Conclusions Distinct patterns of viral RNA evolution may exist shortly after seroconversion in HIV-1 subtype C infection. The study provides better understanding of the early phase of subtype C infection. PMID:19295336

  7. Coral Mucus Is a Hot Spot for Viral Infections.

    PubMed

    Nguyen-Kim, Hanh; Bettarel, Yvan; Bouvier, Thierry; Bouvier, Corinne; Doan-Nhu, Hai; Nguyen-Ngoc, Lam; Nguyen-Thanh, Thuy; Tran-Quang, Huy; Brune, Justine

    2015-09-01

    There is increasing suspicion that viral communities play a pivotal role in maintaining coral health, yet their main ecological traits still remain poorly characterized. In this study, we examined the seasonal distribution and reproduction pathways of viruses inhabiting the mucus of the scleractinians Fungia repanda and Acropora formosa collected in Nha Trang Bay (Vietnam) during an 11-month survey. The strong coupling between epibiotic viral and bacterial abundance suggested that phages are dominant among coral-associated viral communities. Mucosal viruses also exhibited significant differences in their main features between the two coral species and were also remarkably contrasted with their planktonic counterparts. For example, their abundance (inferred from epifluorescence counts), lytic production rates (KCN incubations), and the proportion of lysogenic cells (mitomycin C inductions) were, respectively, 2.6-, 9.5-, and 2.2-fold higher in mucus than in the surrounding water. Both lytic and lysogenic indicators were tightly coupled with temperature and salinity, suggesting that the life strategy of viral epibionts is strongly dependent upon environmental circumstances. Finally, our results suggest that coral mucus may represent a highly favorable habitat for viral proliferation, promoting the development of both temperate and virulent phages. Here, we discuss how such an optimized viral arsenal could be crucial for coral viability by presumably forging complex links with both symbiotic and adjacent nonsymbiotic microorganisms.

  8. Coral Mucus Is a Hot Spot for Viral Infections

    PubMed Central

    Nguyen-Kim, Hanh; Bouvier, Thierry; Bouvier, Corinne; Doan-Nhu, Hai; Nguyen-Ngoc, Lam; Nguyen-Thanh, Thuy; Tran-Quang, Huy; Brune, Justine

    2015-01-01

    There is increasing suspicion that viral communities play a pivotal role in maintaining coral health, yet their main ecological traits still remain poorly characterized. In this study, we examined the seasonal distribution and reproduction pathways of viruses inhabiting the mucus of the scleractinians Fungia repanda and Acropora formosa collected in Nha Trang Bay (Vietnam) during an 11-month survey. The strong coupling between epibiotic viral and bacterial abundance suggested that phages are dominant among coral-associated viral communities. Mucosal viruses also exhibited significant differences in their main features between the two coral species and were also remarkably contrasted with their planktonic counterparts. For example, their abundance (inferred from epifluorescence counts), lytic production rates (KCN incubations), and the proportion of lysogenic cells (mitomycin C inductions) were, respectively, 2.6-, 9.5-, and 2.2-fold higher in mucus than in the surrounding water. Both lytic and lysogenic indicators were tightly coupled with temperature and salinity, suggesting that the life strategy of viral epibionts is strongly dependent upon environmental circumstances. Finally, our results suggest that coral mucus may represent a highly favorable habitat for viral proliferation, promoting the development of both temperate and virulent phages. Here, we discuss how such an optimized viral arsenal could be crucial for coral viability by presumably forging complex links with both symbiotic and adjacent nonsymbiotic microorganisms. PMID:26092456

  9. Sperm viral infection and male infertility: focus on HBV, HCV, HIV, HPV, HSV, HCMV, and AAV.

    PubMed

    Garolla, Andrea; Pizzol, Damiano; Bertoldo, Alessandro; Menegazzo, Massimo; Barzon, Luisa; Foresta, Carlo

    2013-11-01

    Chronic viral infections can infect sperm and are considered a risk factor in male infertility. Recent studies have shown that the presence of HIV, HBV or HCV in semen impairs sperm parameters, DNA integrity, and in particular reduces forward motility. In contrast, very little is known about semen infection with human papillomaviruses (HPV), herpesviruses (HSV), cytomegalovirus (HCMV), and adeno-associated virus (AAV). At present, EU directives for the viral screening of couples undergoing assisted reproduction techniques require only the evaluation of HIV, HBV, and HCV. However, growing evidence suggests that HPV, HSV, and HCMV might play a major role in male infertility and it has been demonstrated that HPV semen infection has a negative influence on sperm parameters, fertilization, and the abortion rate. Besides the risk of horizontal or vertical transmission, the negative impact of any viral sperm infection on male reproductive function seems to be dramatic. In addition, treatment with antiviral and antiretroviral therapies may further affect sperm parameters. In this review we attempted to focus on the interactions between defined sperm viral infections and their association with male fertility disorders. All viruses considered in this article have a potentially negative effect on male reproductive function and dangerous infections can be transmitted to partners and newborns. In light of this evidence, we suggest performing targeted sperm washing procedures for each sperm infection and to strongly consider screening male patients seeking fertility for HPV, HSV, and HCMV, both to avoid viral transmission and to improve assisted or even spontaneous fertility outcome.

  10. Viral genome imaging of hepatitis C virus to probe heterogeneous viral infection and responses to antiviral therapies

    PubMed Central

    Ramanan, Vyas; Trehan, Kartik; Ong, Mei-Lyn; Luna, Joseph M.; Hoffmann, Hans-Heinrich; Espiritu, Christine; Sheahan, Timothy P.; Chandrasekar, Hamsika; Schwartz, Robert E.; Christine, Kathleen S.; Rice, Charles M.; van Oudenaarden, Alexander; Bhatia, Sangeeta N.

    2017-01-01

    Hepatitis C virus (HCV) is a positive single-stranded RNA virus of enormous global health importance, with direct-acting antiviral therapies replacing an immunostimulatory interferon-based regimen. The dynamics of HCV positive and negative-strand viral RNAs (vRNAs) under antiviral perturbations have not been studied at the single-cell level, leaving a gap in our understanding of antiviral kinetics and host-virus interactions. Here, we demonstrate quantitative imaging of HCV genomes in multiple infection models, and multiplexing of positive and negative strand vRNAs and host antiviral RNAs. We capture the varying kinetics with which antiviral drugs with different mechanisms of action clear HCV infection, finding the NS5A inhibitor daclatasvir to induce a rapid decline in negative-strand viral RNAs. We also find that the induction of host antiviral genes upon interferon treatment is positively correlated with viral load in single cells. This study adds smFISH to the toolbox available for analyzing the treatment of RNA virus infections. PMID:27128351

  11. Prophylaxis and therapy of viral infections in pediatric patients treated for malignancy

    PubMed Central

    Licciardello, Maria; Pegoraro, Anna; Cesaro, Simone

    2011-01-01

    Infections are still an important cause of mortality and morbidity in pediatric cancer patients. Most of the febrile episodes in immunocompromised patients are classified as a fever of unknown origin (FUO) while bacteria are the more frequent causes of documented infections. Viral infections are also feared during chemotherapy but less data are available on their incidence and morbidity. We reviewed the literature on incidence, morbidity, and mortality of viral infections in children undergoing chemotherapy and discussed the evidence concerning the prophylaxis and the therapy. PMID:21647278

  12. Prophylaxis and therapy of viral infections in pediatric patients treated for malignancy.

    PubMed

    Licciardello, Maria; Pegoraro, Anna; Cesaro, Simone

    2011-02-24

    Infections are still an important cause of mortality and morbidity in pediatric cancer patients. Most of the febrile episodes in immunocompromised patients are classified as a fever of unknown origin (FUO) while bacteria are the more frequent causes of documented infections. Viral infections are also feared during chemotherapy but less data are available on their incidence and morbidity. We reviewed the literature on incidence, morbidity, and mortality of viral infections in children undergoing chemotherapy and discussed the evidence concerning the prophylaxis and the therapy.

  13. Myocarditis, Disseminated Infection, and Early Viral Persistence Following Experimental Coxsackievirus B Infection of Cynomolgus Monkeys

    PubMed Central

    Cammock, Cheryl E.; Halnon, Nancy J.; Skoczylas, Jill; Blanchard, James; Bohm, Rudolf; Miller, Christopher J.; Lai, Chi; Krogstad, Paul A.

    2013-01-01

    Coxsackievirus B (CVB) infection is a common cause of acute viral myocarditis. The clinical presentation of myocarditis caused by this enterovirus is highly variable, ranging from mildly symptoms to complete hemodynamic collapse. These variations in initial symptoms and in the immediate and long term outcomes of this disease have impeded development of effective treatment strategies. Nine cynomolgus monkeys were inoculated with myocarditic strains of CVB. Virological studies performed up to 28 days post-inoculation demonstrated the development of neutralizing antibody in all animals, and the presence of CVB in plasma. High dose intravenous inoculation (n = 2) resulted in severe disseminated disease, while low dose intravenous (n = 6) or oral infection (1 animal) resulted in clinically unapparent infection. Transient, minor, echocardiographic abnormalities were noted in several animals, but no animals displayed signs of significant acute cardiac failure. Although viremia rapidly resolved, signs of myocardial inflammation and injury were observed in all animals at the time of necropsy, and CVB was detected in postmortem myocardial specimens up to 28 days PI. This non-human primate system replicates many features of illness in acute coxsackievirus myocarditis and demonstrates that myocardial involvement may be common in enteroviral infection; it may provide a model system for testing of treatment strategies for enteroviral infections and acute coxsackievirus myocarditis. PMID:24040287

  14. The V3 Loop of HIV-1 Env Determines Viral Susceptibility to IFITM3 Impairment of Viral Infectivity.

    PubMed

    Wang, Yimeng; Pan, Qinghua; Ding, Shilei; Wang, Zhen; Yu, Jingyou; Finzi, Andrés; Liu, Shan-Lu; Liang, Chen

    2017-04-01

    Interferon-inducible transmembrane proteins (IFITMs) inhibit a broad spectrum of viruses, including HIV-1. IFITM proteins deter HIV-1 entry when expressed in target cells and also impair HIV-1 infectivity when expressed in virus producer cells. However, little is known about how viruses resist IFITM inhibition. In this study, we have investigated the susceptibilities of different primary isolates of HIV-1 to the inhibition of viral infectivity by IFITMs. Our results demonstrate that the infectivity of different HIV-1 primary isolates, including transmitted founder viruses, is diminished by IFITM3 to various levels, with strain AD8-1 exhibiting strong resistance. Further mutagenesis studies revealed that HIV-1 Env, and the V3 loop sequence in particular, determines the extent of inhibition of viral infectivity by IFITM3. IFITM3-sensitive Env proteins are also more susceptible to neutralization by soluble CD4 or the 17b antibody than are IFITM3-resistant Env proteins. Together, data from our study suggest that the propensity of HIV-1 Env to sample CD4-bound-like conformations modulates viral sensitivity to IFITM3 inhibition.IMPORTANCE Results of our study have revealed the key features of the HIV-1 envelope protein that are associated with viral resistance to the IFITM3 protein. IFITM proteins are important effectors in interferon-mediated antiviral defense. A variety of viruses are inhibited by IFITMs at the virus entry step. Although it is known that envelope proteins of several different viruses resist IFITM inhibition, the detailed mechanisms are not fully understood. Taking advantage of the fact that envelope proteins of different HIV-1 strains exhibit different degrees of resistance to IFITM3 and that these HIV-1 envelope proteins share the same domain structure and similar sequences, we performed mutagenesis studies and determined the key role of the V3 loop in this viral resistance phenotype. We were also able to associate viral resistance to IFITM3

  15. Late onset cytopenias following haematopoietic stem cell transplant associated with viral infection and cell specific antibodies.

    PubMed

    Lucas, Geoff; Culliford, Steven; Bendukidze, Nina; Dahlstrom, Julia; Grandage, Victoria; Carpenter, Ben; Hough, Rachael

    2017-02-04

    This report describes a patient who received an allogeneic haematopoietic stem cell transplant and who, following a viral infection, developed late onset cytopenias associated with antibodies against red cells, platelets and granulocytes. Investigation of these cytopenias revealed the presence of lineage specific auto- and allo-antibodies, which were not present in either the donor or in the recipient prior to the viral infection. This case provides further evidence for the concept that viral challenges following HSCT can result in the production of cell specific antibodies that can have significant implications for patient management.

  16. Staphylococcus aureus α-toxin modulates skin host response to viral infection.

    PubMed

    Bin, Lianghua; Kim, Byung Eui; Brauweiler, Anne; Goleva, Elena; Streib, Joanne; Ji, Yinduo; Schlievert, Patrick M; Leung, Donald Y M

    2012-09-01

    Patients with atopic dermatitis (AD) with a history of eczema herpeticum have increased staphylococcal colonization and infections. However, whether Staphylococcus aureus alters the outcome of skin viral infection has not been determined. We investigated whether S aureus toxins modulated host response to herpes simplex virus (HSV) 1 and vaccinia virus (VV) infections in normal human keratinocytes (NHKs) and in murine infection models. NHKs were treated with S aureus toxins before incubation of viruses. BALB/c mice were inoculated with S aureus 2 days before VV scarification. Viral loads of HSV-1 and VV were evaluated by using real-time PCR, a viral plaque-forming assay, and immunofluorescence staining. Small interfering RNA duplexes were used to knockdown the gene expression of the cellular receptor of α-toxin, a disintegrin and metalloprotease 10 (ADAM10). ADAM10 protein and α-toxin heptamers were detected by using Western blot assays. We demonstrate that sublytic staphylococcal α-toxin increases viral loads of HSV-1 and VV in NHKs. Furthermore, we demonstrate in vivo that the VV load is significantly greater (P < .05) in murine skin inoculated with an α-toxin-producing S aureus strain compared with murine skin inoculated with the isogenic α-toxin-deleted strain. The viral enhancing effect of α-toxin is mediated by ADAM10 and is associated with its pore-forming property. Moreover, we demonstrate that α-toxin promotes viral entry in NHKs. The current study introduces the novel concept that staphylococcal α-toxin promotes viral skin infection and provides a mechanism by which S aureus infection might predispose the host toward disseminated viral infections. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  17. Human papillomavirus type 16 viral load measurement as a predictor of infection clearance

    PubMed Central

    Schlecht, Nicolas F.; Ramanakumar, Agnihotram V.; Villa, Luisa L.; Franco, Eduardo L.

    2013-01-01

    Viral load measurements may predict whether human papillomavirus (HPV) type 16 infections may become persistent and eventually lead to cervical lesions. Today, multiple PCR methods exist to estimate viral load. We tested three protocols to investigate viral load as a predictor of HPV clearance. We measured viral load in 418 HPV16-positive cervical smears from 224 women participating in the Ludwig–McGill Cohort Study by low-stringency PCR (LS-PCR) using consensus L1 primers targeting over 40 known HPV types, and quantitative real-time PCR (qRT-PCR) targeting the HPV16 E6 and L1 genes. HPV16 clearance was determined by MY09/11 and PGMY PCR testing on repeated smears collected over 5 years. Correlation between viral load measurements by qRT-PCR (E6 versus L1) was excellent (Spearman’s rank correlation, ρ = 0.88), but decreased for L1 qRT-PCR versus LS-PCR (ρ = 0.61). Viral load by LS-PCR was higher for HPV16 and related types independently of other concurrent HPV infections. Median duration of infection was longer for smears with high copy number by all three PCR protocols (log rank P<0.05). Viral load is inversely related to HPV16 clearance independently of concurrent HPV infections and PCR protocol. PMID:23677791

  18. [Relationship between viral burden in urine and hearing loss in neonates with cytomegalovirus infection].

    PubMed

    Li, Xiao; Chen, Yi-Ji; Li, Lu-Quan

    2011-08-01

    To determine the relationship between viral burden in urine and hearing loss in neonates with cytomegalovirus (CMV) infection. Twenty-two neonates with CMV infection between April 2006 and January 2010 were enrolled. Their viral burden in urine and hearing loss information were studied. The receiver operating characteristic curve (ROC) was constructed and the cutoff was determined based on their medical information. The hearing levels were evaluated by brain stem auditory evoked potential (BAEP) during the age of 3 to 6 months in 20 patients. The viral burden in urine in neonates with abnormal BAEP was higher than that in neonates with normal BAEP (5.06 ± 1.50 vs 3.73 ± 0.86, P<0.05). Hearing loss was predicted with a sensitivity of 0.545 and a specificity of 1.0 by using ROC at the cutoff point of 5.1 which were defined after logarithmic conversion at 1.27×10(5) copies/mL of CMV burden in urine. The incidence of hearing loss during the age of 3 to 6 months was strikingly higher in high viral burden group than that in low viral load group (P<0.05). The viral burden in urine can predict the possibility of hearing loss in neonates with CMV infection. Hearing loss is likely to be developed when viral burden in urine ≥1.27×10(5) copies/mL in neonates with CMV infection.

  19. Limiting influenza virus, HIV and dengue virus infection by targeting viral proteostasis

    PubMed Central

    Heaton, Nicholas S.; Moshkina, Natasha; Fenouil, Romain; Gardner, Thomas J.; Aguirre, Sebastian; Shah, Priya S.; Zhao, Nan; Manganaro, Lara; Hultquist, Judd; Noel, Justine; Sachs, David; Hamilton, Jennifer; Leon, Paul E.; Chawdury, Amit; Tripathy, Shashank; Melegari, Camilla; Campisi, Laura; Hai, Rong; Metreveli, Giorgi; Gamarnik, Andrea V.; García-Sastre, Adolfo; Greenbaum, Benjamin; Simon, Viviana; Fernandez-Sesma, Ana; Krogan, Nevan; Mulder, Lubbertus C.F.; van Bakel, Harm; Tortorella, Domenico; Taunton, Jack; Palese, Peter; Marazzi, Ivan

    2016-01-01

    Viruses are obligate parasites as they require the machinery of the host cell to replicate. Inhibition of host factors co-opted during active infection is a strategy 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, 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

  20. Enhanced enteroviral infectivity via viral protease-mediated cleavage of Grb2-associated binder 1

    PubMed Central

    Deng, Haoyu; Fung, Gabriel; Shi, Junyan; Xu, Suowen; Wang, Chen; Yin, Meimei; Hou, Jun; Zhang, Jingchun; Jin, Zheng-Gen; Luo, Honglin

    2015-01-01

    Coxsackievirus B3 (CVB3), an important human causative pathogen for viral myocarditis, pancreatitis, and meningitis, has evolved different strategies to manipulate the host signaling machinery to ensure successful viral infection. We previously revealed a crucial role for the ERK1/2 signaling pathway in regulating viral infectivity. However, the detail mechanism remains largely unknown. Grb2-associated binder 1 (GAB1) is an important docking protein responsible for intracellular signaling assembly and transduction. In this study, we demonstrated that GAB1 was proteolytically cleaved after CVB3 infection at G175 and G436 by virus-encoded protease 2Apro, independent of caspase activation. Knockdown of GAB1 resulted in a significant reduction of viral protein expression and virus titers. Moreover, we showed that virus-induced cleavage of GAB1 is beneficial to viral growth as the N-terminal proteolytic product of GAB1 (GAB1-N1–174) further enhances ERK1/2 activation and promotes viral replication. Our results collectively suggest that CVB3 targets host GAB1 to generate a GAB1-N1–174 fragment that enhances viral infectivity, at least in part, via activation of the ERK pathway. The findings in this study suggest a novel mechanism that CVB3 employs to subvert the host signaling and facilitate consequent viral replication.—Deng, H., Fung, G., Shi, J., Xu, S., Wang, C., Yin, M., Hou, J., Zhang, J., Jin, Z.-G., Luo, H. Enhanced enteroviral infectivity via viral protease-mediated cleavage of Grb2-associated binder 1. PMID:26183772

  1. Cotton Leaf Curl Multan Virus-Derived Viral Small RNAs Can Target Cotton Genes to Promote Viral Infection

    PubMed Central

    Wang, Jinyan; Tang, Yafei; Yang, Yuwen; Ma, Na; Ling, Xitie; Kan, Jialiang; He, Zifu; Zhang, Baolong

    2016-01-01

    RNA silencing is a conserved mechanism in plants that targets viruses. Viral small RNAs (vsiRNAs) can be generated from viral double-stranded RNA replicative intermediates within the infected host, or from host RNA-dependent RNA polymerases activity on viral templates. The abundance and profile of vsiRNAs in viral infections have been reported previously. However, the involvement of vsiRNAs during infection of the Geminiviridae family member cotton leaf curl virus (CLCuD), which causes significant economic losses in cotton growing regions, remains largely uncharacterized. Cotton leaf curl Multan virus (CLCuMuV) associated with a betasatellite called Cotton leaf curl Multan betasatellite (CLCuMuB) is a major constraint to cotton production in South Asia and is now established in Southern China. In this study, we obtained the profiles of vsiRNAs from CLCuMV and CLCuMB in infected upland cotton (Gossypium hirsutum) plants by deep sequencing. Our data showed that vsiRNA that were derived almost equally from sense and antisense CLCuD DNA strands accumulated preferentially as 21- and 22-nucleotide (nt) small RNA population and had a cytosine bias at the 5′-terminus. Polarity distribution revealed that vsiRNAs were almost continuously present along the CLCuD genome and hotspots of sense and antisense strands were mainly distributed in the Rep proteins region of CLCuMuV and in the C1 protein of CLCuMuB. In addition, hundreds of host transcripts targeted by vsiRNAs were predicted, many of which encode transcription factors associated with biotic and abiotic stresses. Quantitative real-time polymerase chain reaction analysis of selected potential vsiRNA targets showed that some targets were significantly down-regulated in CLCuD-infected cotton plants. We also verified the potential function of vsiRNA targets that may be involved in CLCuD infection by virus-induced gene silencing (VIGS) and 5′-rapid amplification of cDNA end (5′-RACE). Here, we provide the first report

  2. Viral infections in type 1 diabetes mellitus--why the β cells?

    PubMed

    Op de Beeck, Anne; Eizirik, Decio L

    2016-05-01

    Type 1 diabetes mellitus (T1DM) is caused by progressive autoimmune-mediated loss of pancreatic β-cell mass via apoptosis. The onset of T1DM depends on environmental factors that interact with predisposing genes to induce an autoimmune assault against β cells. Epidemiological, clinical and pathology studies in humans support viral infection--particularly by enteroviruses (for example, coxsackievirus)--as an environmental trigger for the development of T1DM. Many candidate genes for T1DM, such as MDA5, PTPN2 and TYK2, regulate antiviral responses in both β cells and the immune system. Cellular permissiveness to viral infection is modulated by innate antiviral responses that vary among different tissues or cell types. Some data indicate that pancreatic islet α cells trigger a more efficient antiviral response to infection with diabetogenic viruses than do β cells, and so are able to eradicate viral infections without undergoing apoptosis. This difference could account for the varying ability of islet-cell subtypes to clear viral infections and explain why chronically infected pancreatic β cells, but not α cells, are targeted by an autoimmune response and killed during the development of T1DM. These issues and attempts to target viral infection as a preventive therapy for T1DM are discussed in the present Review.

  3. [Role of combination NK/KIRs in the natural history of viral infections.

    PubMed

    Colomba, Claudia; Cascio, Antonio; Caruso, Calogero; Trizzino, Marcello; Gioè, Claudia; Guadagnino, Giuliana; Tuttolomondo, Antonino; Pinto, Antonio; Saracino, Annalisa; Angarano, Gioacchino; Di Bona, Danilo

    2017-01-01

    Immunological mechanisms involved in the genesis of the immune response against viral infections take into account the activation of both innate adaptative response. Innate immune defenses trigger a rapid local response, which is often sufficient to control viral infection, and promotes the subsequent activation of specific immune defenses. Natural killer (NK) cells that constitute a subpopulation of lymphocyte-related cells are a key factor of innate immune response and play a role in defense against viral infections by killing infected cells or by producing cytokines and interacting with adaptative immune system's cells. Killer immunoglobulin-like receptors (KIRs) regulate the activation of NK cells through their interaction with human leukocyte antigens (HLA). KIRs and HLA loci are highly polymorphic and certain HLA-KIRs combinations have been found to protect against viral infections. In this study we review how the KIRs/HLA repertoire may influence the course of hepatitis B virus (HBV), hepatitis C virus (HCV), cytomegalovirus (CMV) and Herpes Simplex Virus 1 (HSV-1) infection. Results of our study suggest that a combination of KIRs/HLA gene/alleles is able to predict the outcome of viral infection and allows to plan successful customized therapeutic strategies.

  4. Viral infections in type 1 diabetes mellitus — why the β cells?

    PubMed Central

    2017-01-01

    Type 1 diabetes mellitus (T1DM) is caused by progressive autoimmune-mediated loss of pancreatic β-cell mass via apoptosis. The onset of T1DM depends on environmental factors that interact with predisposing genes to induce an autoimmune assault against β cells. Epidemiological, clinical and pathology studies in humans support viral infection — particularly by enteroviruses (for example, coxsackievirus) — as an environmental trigger for the development of T1DM. Many candidate genes for T1DM, such as MDA5, PTPN2 and TYK2, regulate antiviral responses in both β cells and the immune system. Cellular permissiveness to viral infection is modulated by innate antiviral responses that vary among different tissues or cell types. Some data indicate that pancreatic islet α cells trigger a more efficient antiviral response to infection with diabetogenic viruses than do β cells, and so are able to eradicate viral infections without undergoing apoptosis. This difference could account for the varying ability of islet-cell subtypes to clear viral infections and explain why chronically infected pancreatic β cells, but not α cells, are targeted by an autoimmune response and killed during the development of T1DM. These issues and attempts to target viral infection as a preventive therapy for T1DM are discussed in the present Review. PMID:27020257

  5. Lipid rafts both in cellular membrane and viral envelope are critical for PRRSV efficient infection.

    PubMed

    Yang, Qian; Zhang, Qiong; Tang, Jun; Feng, Wen-Hai

    2015-10-01

    Porcine reproductive and respiratory syndrome virus (PRRSV) represents a significantly economical challenge to the swine industry worldwide. In this study, we investigated the importance of cellular and viral lipid rafts in PRRSV infection. First, we demonstrated that PRRSV glycoproteins, Gp3 and Gp4, were associated with lipid rafts during viral entry, and disruption of cellular lipid rafts inhibited PRRSV entry. We also showed the raft-location of CD163, which might contribute to the glycoproteins-raft association. Subsequently, raft disruption caused a significant reduction of viral RNA production. Moreover, Nsp9 was shown to be distributed in rafts, suggesting that rafts probably serve as a platform for PRRSV replication. Finally, we confirmed that disassembly of rafts on the virus envelope may affect the integrity of PRRSV particles and cause the leakage of viral proteins, which impaired PRRSV infectivity. These findings might provide insights on our understanding of the mechanism of PRRSV infection.

  6. Deciphering Multiplicity of HIV-1C Infection: Transmission of Closely Related Multiple Viral Lineages

    PubMed Central

    Novitsky, Vlad; Moyo, Sikhulile; Wang, Rui; Gaseitsiwe, Simani; Essex, M.

    2016-01-01

    Background A single viral variant is transmitted in the majority of HIV infections. However, about 20% of heterosexually transmitted HIV infections are caused by multiple viral variants. Detection of transmitted HIV variants is not trivial, as it involves analysis of multiple viral sequences representing intra-host HIV-1 quasispecies. Methodology We distinguish two types of multiple virus transmission in HIV infection: (1) HIV transmission from the same source, and (2) transmission from different sources. Viral sequences representing intra-host quasispecies in a longitudinally sampled cohort of 42 individuals with primary HIV-1C infection in Botswana were generated by single-genome amplification and sequencing and spanned the V1C5 region of HIV-1C env gp120. The Maximum Likelihood phylogeny and distribution of pairwise raw distances were assessed at each sampling time point (n = 217; 42 patients; median 5 (IQR: 4–6) time points per patient, range 2–12 time points per patient). Results Transmission of multiple viral variants from the same source (likely from the partner with established HIV infection) was found in 9 out of 42 individuals (21%; 95 CI 10–37%). HIV super-infection was identified in 2 patients (5%; 95% CI 1–17%) with an estimated rate of 3.9 per 100 person-years. Transmission of multiple viruses combined with HIV super-infection at a later time point was observed in one individual. Conclusions Multiple HIV lineages transmitted from the same source produce a monophyletic clade in the inferred phylogenetic tree. Such a clade has transiently distinct sub-clusters in the early stage of HIV infection, and follows a predictable evolutionary pathway. Over time, the gap between initially distinct viral lineages fills in and initially distinct sub-clusters converge. Identification of cases with transmission of multiple viral lineages from the same source needs to be taken into account in cross-sectional estimation of HIV recency in epidemiological and

  7. No evidence of an increase of bacterial and viral infections following Measles, Mumps and Rubella vaccine.

    PubMed

    Stowe, Julia; Andrews, Nick; Taylor, Brent; Miller, Elizabeth

    2009-02-25

    The suggestion that multi-antigen vaccines might overload the immune system has led to calls for single antigen vaccines. In 2003 we showed that rather than an increase there appeared to be a reduced risk of severe bacterial infection in the three months following Measles, Mumps and Rubella vaccine (MMR). The present analysis of illnesses in a general population is based on an additional 10 years of data for bacterial infections and also includes admissions with viral infections. Analyses were carried out using the self-controlled case-series method and separately for bacterial and viral infection cases, using risk periods of 0-30 days, 31-60 days and 61-90 days post MMR vaccine. An analysis was also carried out for those cases which were given MMR and Meningococcal serogroup C (MCC) vaccines concomitantly. A reduced risk was seen in the 0-30-day period for both bacterial infection (relative incidence=0.68, 95% CI 0.54-0.86) and viral infections (relative incidence=0.68, 95% CI 0.49-0.93). There was no increased risk in any period when looking at combined viral or bacterial infections or for individual infections with the single exception of an increased risk in the 31-60 days post vaccination period for herpes infections (relative incidence=1.69, 95% CI 1.06-2.70). For the children given Meningococcal group C vaccines concomitantly no significantly increased risk was seen in either the bacterial (relative incidence=0.54, 95% CI 0.26-1.13) or viral cases (relative incidence=0.46, 95% CI 0.11-1.93). Our study confirms that the MMR vaccine does not increase the risk of invasive bacterial or viral infection in the 90 days after the vaccination and does not support the hypothesis that there is an induced immune deficiency due to overload from multi-antigen vaccines.

  8. The Toll-Dorsal Pathway Is Required for Resistance to Viral Oral Infection in Drosophila

    PubMed Central

    Ferreira, Álvaro Gil; Naylor, Huw; Esteves, Sara Santana; Pais, Inês Silva; Martins, Nelson Eduardo; Teixeira, Luis

    2014-01-01

    Pathogen entry route can have a strong impact on the result of microbial infections in different hosts, including insects. Drosophila melanogaster has been a successful model system to study the immune response to systemic viral infection. Here we investigate the role of the Toll pathway in resistance to oral viral infection in D. melanogaster. We show that several Toll pathway components, including Spätzle, Toll, Pelle and the NF-kB-like transcription factor Dorsal, are required to resist oral infection with Drosophila C virus. Furthermore, in the fat body Dorsal is translocated from the cytoplasm to the nucleus and a Toll pathway target gene reporter is upregulated in response to Drosophila C Virus infection. This pathway also mediates resistance to several other RNA viruses (Cricket paralysis virus, Flock House virus, and Nora virus). Compared with control, viral titres are highly increased in Toll pathway mutants. The role of the Toll pathway in resistance to viruses in D. melanogaster is restricted to oral infection since we do not observe a phenotype associated with systemic infection. We also show that Wolbachia and other Drosophila-associated microbiota do not interact with the Toll pathway-mediated resistance to oral infection. We therefore identify the Toll pathway as a new general inducible pathway that mediates strong resistance to viruses with a route-specific role. These results contribute to a better understanding of viral oral infection resistance in insects, which is particularly relevant in the context of transmission of arboviruses by insect vectors. PMID:25473839

  9. Viral targeting of fibroblastic reticular cells contributes to immunosuppression and persistence during chronic infection.

    PubMed

    Mueller, Scott N; Matloubian, Mehrdad; Clemens, Daniel M; Sharpe, Arlene H; Freeman, Gordon J; Gangappa, Shivaprakash; Larsen, Christian P; Ahmed, Rafi

    2007-09-25

    Many chronic viral infections are marked by pathogen persistence and a generalized immunosuppression. The exact mechanisms by which this occurs are still unknown. Using a mouse model of persistent lymphocytic choriomeningitis virus (LCMV) infection, we demonstrate viral targeting of fibroblastic reticular cells (FRC) in the lymphoid organs. The FRC stromal networks are critical for proper lymphoid architecture and function. High numbers of FRC were infected by LCMV clone 13, which causes a chronic infection, whereas few were infected by the acute strain, LCMV Armstrong. The function of the FRC conduit network was altered after clone 13 infection by the action of CD8(+) T cells. Importantly, expression of the inhibitory programmed death ligand 1, which was up-regulated on FRC after infection, reduced early CD8(+) T cell-mediated immunopathology and prevented destruction of the FRC architecture in the spleen. Together, this reveals an important tropism during a persistent viral infection. These data also suggest that the inhibitory PD-1 pathway, which likely evolved to prevent excessive immunopathology, may contribute to viral persistence in FRC during chronic infection.

  10. Using experimental human influenza infections to validate a viral dynamic model and the implications for prediction.

    PubMed

    Chen, S C; You, S H; Liu, C Y; Chio, C P; Liao, C M

    2012-09-01

    The aim of this work was to use experimental infection data of human influenza to assess a simple viral dynamics model in epithelial cells and better understand the underlying complex factors governing the infection process. The developed study model expands on previous reports of a target cell-limited model with delayed virus production. Data from 10 published experimental infection studies of human influenza was used to validate the model. Our results elucidate, mechanistically, the associations between epithelial cells, human immune responses, and viral titres and were supported by the experimental infection data. We report that the maximum total number of free virions following infection is 10(3)-fold higher than the initial introduced titre. Our results indicated that the infection rates of unprotected epithelial cells probably play an important role in affecting viral dynamics. By simulating an advanced model of viral dynamics and applying it to experimental infection data of human influenza, we obtained important estimates of the infection rate. This work provides epidemiologically meaningful results, meriting further efforts to understand the causes and consequences of influenza A infection.

  11. Cellular Immune Responses and Viral Diversity in Individuals Treated during Acute and Early HIV-1 Infection

    PubMed Central

    Altfeld, Marcus; Rosenberg, Eric S.; Shankarappa, Raj; Mukherjee, Joia S.; Hecht, Frederick M.; Eldridge, Robert L.; Addo, Marylyn M.; Poon, Samuel H.; Phillips, Mary N.; Robbins, Gregory K.; Sax, Paul E.; Boswell, Steve; Kahn, James O.; Brander, Christian; Goulder, Philip J.R.; Levy, Jay A.; Mullins, James I.; Walker, Bruce D.

    2001-01-01

    Immune responses induced during the early stages of chronic viral infections are thought to influence disease outcome. Using HIV as a model, we examined virus-specific cytotoxic T lymphocytes (CTLs), T helper cells, and viral genetic diversity in relation to duration of infection and subsequent response to antiviral therapy. Individuals with acute HIV-1 infection treated before seroconversion had weaker CTL responses directed at fewer epitopes than persons who were treated after seroconversion. However, treatment-induced control of viremia was associated with the development of strong T helper cell responses in both groups. After 1 yr of antiviral treatment initiated in acute or early infection, all epitope-specific CTL responses persisted despite undetectable viral loads. The breadth and magnitude of CTL responses remained significantly less in treated acute infection than in treated chronic infection, but viral diversity was also significantly less with immediate therapy. We conclude that early treatment of acute HIV infection leads to a more narrowly directed CTL response, stronger T helper cell responses, and a less diverse virus population. Given the need for T helper cells to maintain effective CTL responses and the ability of virus diversification to accommodate immune escape, we hypothesize that early therapy of primary infection may be beneficial despite induction of less robust CTL responses. These data also provide rationale for therapeutic immunization aimed at broadening CTL responses in treated primary HIV infection. PMID:11148221

  12. Bovine viral diarrhea virus infections: manifestations of infection and recent advances in understanding pathogenesis and control.

    PubMed

    Brodersen, B W

    2014-03-01

    Bovine viral diarrhea virus (BVDV) continues to be of economic significance to the livestock industry in terms of acute disease and fetal loss. Many of the lesions relating to BVDV infection have been well described previously. The virus is perpetuated in herds through the presence of calves that are persistently infected. Relationships between various species and biotypes of BVDV and host defenses are increasingly understood. Understanding of the host defense mechanisms of innate immunity and adaptive immunity continues to improve, and the effects of the virus on these immune mechanisms are being used to explain how persistent infection develops. The noncytopathic biotype of BVDV plays the major role in its effects on the host defenses by inhibiting various aspects of the innate immune system and creation of immunotolerance in the fetus during early gestation. Recent advances have allowed for development of affordable test strategies to identify and remove persistently infected animals. With these improved tests and removal strategies, the livestock industry can begin more widespread effective control programs.

  13. Morphological, Biochemical, and Functional Study of Viral Replication Compartments Isolated from Adenovirus-Infected Cells

    PubMed Central

    Hidalgo, Paloma; Anzures, Lourdes; Hernández-Mendoza, Armando; Guerrero, Adán; Wood, Christopher D.; Valdés, Margarita; Dobner, Thomas

    2016-01-01

    ABSTRACT Adenovirus (Ad) replication compartments (RC) are nuclear microenvironments where the viral genome is replicated and a coordinated program of late gene expression is established. These virus-induced nuclear sites seem to behave as central hubs for the regulation of virus-host cell interactions, since proteins that promote efficient viral replication as well as factors that participate in the antiviral response are coopted and concentrated there. To gain further insight into the activities of viral RC, here we report, for the first time, the morphology, composition, and activities of RC isolated from Ad-infected cells. Morphological analyses of isolated RC particles by superresolution microscopy showed that they were indistinguishable from RC within infected cells and that they displayed a dynamic compartmentalization. Furthermore, the RC-containing fractions (RCf) proved to be functional, as they directed de novo synthesis of viral DNA and RNA as well as RNA splicing, activities that are associated with RC in vivo. A detailed analysis of the production of viral late mRNA from RCf at different times postinfection revealed that viral mRNA splicing occurs in RC and that the synthesis, posttranscriptional processing, and release from RC to the nucleoplasm of individual viral late transcripts are spatiotemporally separate events. The results presented here demonstrate that RCf are a powerful system for detailed study into RC structure, composition, and activities and, as a result, the determination of the molecular mechanisms that induce the formation of these viral sites of adenoviruses and other nuclear-replicating viruses. IMPORTANCE RC may represent molecular hubs where many aspects of virus-host cell interaction are controlled. Here, we show by superresolution microscopy that RCf have morphologies similar to those of RC within Ad-infected cells and that they appear to be compartmentalized, as nucleolin and DBP display different localization in the

  14. Dynamics of viral replication in infants with vertically acquired human immunodeficiency virus type 1 infection.

    PubMed Central

    De Rossi, A; Masiero, S; Giaquinto, C; Ruga, E; Comar, M; Giacca, M; Chieco-Bianchi, L

    1996-01-01

    About one-third of vertically HIV-1 infected infants develop AIDS within the first months of life; the remainder show slower disease progression. We investigated the relationship between the pattern of HIV-1 replication early in life and disease outcome in eleven infected infants sequentially studied from birth. Viral load in cells and plasma was measured by highly sensitive competitive PCR-based methods. Although all infants showed an increase in the indices of viral replication within their first weeks of life, three distinct patterns emerged: (a) a rapid increase in plasma viral RNA and cell-associated proviral DNA during the first 4-6 wk, reaching high steady state levels (> 1,000 HIV-1 copies/10(5) PBMC and > 1,000,000 RNA copies/ml plasma) within 2-3 mo of age; (b) a similar initial rapid increase in viral load, followed by a 2.5-50-fold decline in viral levels; (c) a significantly lower (> 10-fold) viral increase during the first 4-6 wk of age. All infants displaying the first pattern developed early AIDS, while infants with slower clinical progression exhibited the second or third pattern. These findings demonstrate that the pattern of viral replication and clearance in the first 2-3 mo of life is strictly correlated with, and predictive of disease evolution in vertically infected infants. PMID:8567951

  15. Transient Viremia, Plasma Viral Load, and Reservoir Replenishment in HIV-Infected Patients on Antiretroviral Therapy

    PubMed Central

    Jones, Laura E.; Perelson, Alan S.

    2008-01-01

    Summary When antiretroviral therapy (ART) is administered for long periods to HIV-1–infected patients, most achieve viral loads that are “undetectable” by standard assay methods (ie, HIV-1 RNA <50 copies/mL). Despite sustaining viral loads lower than the level of detection, a number of patients experience unexplained episodes of transient viremia or viral “blips.” We propose that transient activation of the immune system by infectious agents may explain these episodes of viremia. Using 2 different mathematical models, one in which blips arise because of target cell activation and subsequent infection and another in which latent cell activation generates blips, we establish a nonlinear (power law) relationship between blip amplitude and viral load (under ART) that suggest blips should be of lower amplitude, and thus harder to detect, as increasingly potent therapy is used. This effect can be more profound than is predicted by simply lowering the baseline viral load from which blips originate. Finally, we suggest that sporadic immune activation may elevate the level of chronically infected cells and replenish viral reservoirs, including the latent cell reservoir, providing a mechanism for recurrent viral blips and low levels of viremia under ART. PMID:17496565

  16. Viral Co-Infections in Pediatric Patients Hospitalized with Lower Tract Acute Respiratory Infections

    PubMed Central

    Cebey-López, Miriam; Herberg, Jethro; Pardo-Seco, Jacobo; Gómez-Carballa, Alberto; Martinón-Torres, Nazareth; Salas, Antonio; Martinón-Sánchez, José María; Gormley, Stuart; Sumner, Edward; Fink, Colin; Martinón-Torres, Federico

    2015-01-01

    Background Molecular techniques can often reveal a broader range of pathogens in respiratory infections. We aim to investigate the prevalence and age pattern of viral co-infection in children hospitalized with lower tract acute respiratory infection (LT-ARI), using molecular techniques. Methods A nested polymerase chain reaction approach was used to detect Influenza (A, B), metapneumovirus, respiratory syncytial virus (RSV), parainfluenza (1–4), rhinovirus, adenovirus (A—F), bocavirus and coronaviruses (NL63, 229E, OC43) in respiratory samples of children with acute respiratory infection prospectively admitted to any of the GENDRES network hospitals between 2011–2013. The results were corroborated in an independent cohort collected in the UK. Results A total of 204 and 97 nasopharyngeal samples were collected in the GENDRES and UK cohorts, respectively. In both cohorts, RSV was the most frequent pathogen (52.9% and 36.1% of the cohorts, respectively). Co-infection with multiple viruses was found in 92 samples (45.1%) and 29 samples (29.9%), respectively; this was most frequent in the 12–24 months age group. The most frequently observed co-infection patterns were RSV—Rhinovirus (23 patients, 11.3%, GENDRES cohort) and RSV—bocavirus / bocavirus—influenza (5 patients, 5.2%, UK cohort). Conclusion The presence of more than one virus in pediatric patients admitted to hospital with LT-ARI is very frequent and seems to peak at 12–24 months of age. The clinical significance of these findings is unclear but should warrant further analysis. PMID:26332375

  17. Type-I Interferon Responses: From Friend to Foe in the Battle against Chronic Viral Infection

    PubMed Central

    Murira, Armstrong; Lamarre, Alain

    2016-01-01

    Type I interferons (IFN-I) have long been heralded as key contributors to effective antiviral responses. More widely understood in the context of acute viral infection, the role of this pleiotropic cytokine has been characterized as triggering antiviral states in cells and potentiating adaptive immune responses. Upon induction in the innate immune response, IFN-I triggers the expression of interferon-stimulated genes (ISGs), which upregulate the effector function of immune cells (e.g., dendritic cells, B cells, and T cells) toward successful resolution of infections. However, emerging lines of evidence reveal that viral persistence in the course of chronic infections could be driven by deleterious immunomodulatory effects upon sustained IFN-I expression. In this setting, elevation of IFN-I and ISGs is directly correlated to viral persistence and elevated viral loads. It is important to note that the correlation among IFN-I expression, ISGs, and viral persistence may be a cause or effect of chronic infection and this is an important distinction to make toward establishing the dichotomous nature of IFN-I responses. The aim of this mini review is to (i) summarize the interaction between IFN-I and downstream effector responses and therefore (ii) delineate the function of this cytokine on positive and negative immunoregulation in chronic infection. This is a significant consideration given the current therapeutic administration of IFN-I in chronic viral infections whose therapeutic significance is projected to continue despite emergence of increasingly efficacious antiviral regimens. Furthermore, elucidation of the interplay between virus and the antiviral response in the context of IFN-I will elucidate avenues toward more effective therapeutic and prophylactic measures against chronic viral infections. PMID:28066419

  18. Rapid, targeted and culture-free viral infectivity assay in drop-based microfluidics.

    PubMed

    Tao, Ye; Rotem, Assaf; Zhang, Huidan; Chang, Connie B; Basu, Anindita; Kolawole, Abimbola O; Koehler, Stephan A; Ren, Yukun; Lin, Jeffrey S; Pipas, James M; Feldman, Andrew B; Wobus, Christiane E; Weitz, David A

    2015-10-07

    A key viral property is infectivity, and its accurate measurement is crucial for the understanding of viral evolution, disease and treatment. Currently viral infectivity is measured using plaque assays, which involve prolonged culturing of host cells, and whose measurement is unable to differentiate between specific strains and is prone to low number fluctuation. We developed a rapid, targeted and culture-free infectivity assay using high-throughput drop-based microfluidics. Single infectious viruses are incubated in a large number of picoliter drops with host cells for one viral replication cycle followed by in-drop gene-specific amplification to detect infection events. Using murine noroviruses (MNV) as a model system, we measure their infectivity and determine the efficacy of a neutralizing antibody for different variants of MNV. Our results are comparable to traditional plaque-based assays and plaque reduction neutralization tests. However, the fast, low-cost, highly accurate genomic-based assay promises to be a superior method for drug screening and isolation of resistant viral strains. Moreover our technique can be adapted to measuring the infectivity of other pathogens, such as bacteria and fungi.

  19. Progress in Treatment of Viral Infections in Children with Acute Lymphoblastic Leukemia

    PubMed Central

    Moschovi, Maria; Adamaki, Maria; Vlahopoulos, Spiros A.

    2016-01-01

    In children, the most commonly encountered type of leukemia is acute lymphoblastic leukemia (ALL). An important source of morbidity and mortality in ALL are viral infections. Even though allogeneic transplantations, which are often applied also in ALL, carry a recognized risk for viral infections, there are multiple factors that make ALL patients susceptible to viral infections. The presence of those factors has an influence in the type and severity of infections. Currently available treatment options do not guarantee a positive outcome for every case of viral infection in ALL, without significant side effects. Side effects can have very serious consequences for the ALL patients, which include nephrotoxicity. For this reason a number of strategies for personalized intervention have been already clinically tested, and experimental approaches are being developed. Adoptive immunotherapy, which entails administration of ex vivo grown immune cells to a patient, is a promising approach in general, and for transplant recipients in particular. The ex vivo grown cells are aimed to strengthen the immune response to the virus that has been identified in the patients’ blood and tissue samples. Even though many patients with weakened immune system can benefit from progress in novel approaches, a viral infection still poses a very significant risk for many patients. Therefore, preventive measures and supportive care are very important for ALL patients. PMID:27471584

  20. Productive infection of human immunodeficiency virus type 1 in dendritic cells requires fusion-mediated viral entry

    SciTech Connect

    Janas, Alicia M.; Dong, Chunsheng; Wang Jianhua; Wu Li

    2008-06-05

    Human immunodeficiency virus type 1 (HIV-1) enters dendritic cells (DCs) through endocytosis and viral receptor-mediated fusion. Although endocytosis-mediated HIV-1 entry can generate productive infection in certain cell types, including human monocyte-derived macrophages, productive HIV-1 infection in DCs appears to be dependent on fusion-mediated viral entry. It remains to be defined whether endocytosed HIV-1 in DCs can initiate productive infection. Using HIV-1 infection and cellular fractionation assays to measure productive viral infection and entry, here we show that HIV-1 enters monocyte-derived DCs predominately through endocytosis; however, endocytosed HIV-1 cannot initiate productive HIV-1 infection in DCs. In contrast, productive HIV-1 infection in DCs requires fusion-mediated viral entry. Together, these results provide functional evidence in understanding HIV-1 cis-infection of DCs, suggesting that different pathways of HIV-1 entry into DCs determine the outcome of viral infection.

  1. NADPH oxidases (NOXes) and reactive oxygen in viral infections, with emphasis on influenza

    USDA-ARS?s Scientific Manuscript database

    The body makes highly reactive molecules, at times as a by-product of other processes, but also sometimes intentionally. This book chapter reviews both the generation of these molecules and how the molecules can impact viral infections. There is a specific focus on influenza virus infections....

  2. Evidence for persistent bovine viral diarrhea virus infection in a captive mountain goat (Oreamnos americanus)

    USDA-ARS?s Scientific Manuscript database

    Bovine viral diarrhea viruses (BVDV) are pestiviruses that have been isolated from domestic and wild ruminants, and there is serologic evidence of pestiviral infection in more than 40 species of free-ranging and captive mammals. Vertical transmission can produce persistently infected animals that ar...

  3. A Rapid Blood Test To Determine the Active Status and Duration of Acute Viral Infection.

    PubMed

    Zheng, Tianyu; Finn, Caroline; Parrett, Christopher J; Dhume, Kunal; Hwang, Ji Hae; Sidhom, David; Strutt, Tara M; Li Sip, Yuen Yee; McKinstry, Karl K; Huo, Qun

    2017-09-20

    The ability to rapidly detect and diagnose acute viral infections is crucial for infectious disease control and management. Serology testing for the presence of virus-elicited antibodies in blood is one of the methods used commonly for clinical diagnosis of viral infections. However, standard serology-based tests have a significant limitation: they cannot easily distinguish active from past, historical infections. As a result, it is difficult to determine whether a patient is currently infected with a virus or not, and on an optimal course of action, based off of positive serology testing responses. Here, we report a nanoparticle-enabled blood test that can help overcome this major challenge. The new test is based on the analysis of virus-elicited immunoglobulin G (IgG) antibody present in the protein corona of a gold nanoparticle surface upon mixing the gold nanoparticles with blood sera. Studies conducted on mouse models of influenza A virus infection show that the test gives positive responses only in the presence of a recent acute viral infection, approximately between day 14 and day 21 following the infection, and becomes negative thereafter. When used together with the traditional serology testing, the nanoparticle test can determine clearly whether a positive serology response is due to a recent or historical viral infection. This new blood test can provide critical clinical information needed to optimize further treatment and/or to determine if further quarantining should be continued.

  4. Management of Respiratory Viral Infections in Hematopoietic Cell Transplant Recipients and Patients With Hematologic Malignancies

    PubMed Central

    Chemaly, Roy F.; Shah, Dimpy P.; Boeckh, Michael J.

    2014-01-01

    Despite preventive strategies and increased awareness, a high incidence of respiratory viral infections still occur in patients with hematologic malignancies (HMs) and in recipients of hematopoietic cell transplant (HCT). Progression of these viral infections to lower respiratory tract may prove fatal, especially in HCT recipients. Increasing evidence on the successful use of ribavirin (alone or in combination with immunomodulators) for the treatment of respiratory syncytial virus infections in HM patients and HCT recipients is available from retrospective studies; however, prospective clinical trials are necessary to establish its efficacy with confidence. The impact on progression to pneumonitis and/or mortality of treating parainfluenza virus infections with available (ribavirin) or investigational (DAS181) antiviral agents still needs to be determined. Influenza infections have been successfully treated with neuraminidase inhibitors (oseltamivir or zanamivir); however, the efficacy of these agents for influenza pneumonia has not been established, and immunocompromised patients are highly susceptible to emergence of antiviral drug resistance, most probably due to prolonged viral shedding. Infection control measures and an appreciation of the complications following respiratory viral infections in immunocompromised patients remain crucial for reducing transmission. Future studies should focus on strategies to identify patients at high risk for increased morbidity and mortality from these infections and to determine the efficacy of novel or available antiviral drugs. PMID:25352629

  5. Long-term clincopathological characteristics of alpacas naturally infected with bovine viral diarrhea virus type Ib

    USDA-ARS?s Scientific Manuscript database

    Background: Substantial bovine viral diarrhea virus (BVDV)-related production losses in North American alpaca herds have been associated with BVDV type Ib infection. Objectives: To classify and differentiate the long-term clinicopathological characteristics of BVDV type Ib infection of alpaca crias,...

  6. The effects of exposure of susceptible alpacas to alpacas persistently infected with bovine viral diarrhea virus

    USDA-ARS?s Scientific Manuscript database

    Reports of bovine viral diarrhea virus (BVDV) infections in alpacas have been increasing over the past several years but much is still unknown about the mechanisms of disease in this species. This report describes research performed to characterize the transmission of BVDV from persistently infected...

  7. First report of bovine viral diarrhoea virus-2 infection in cattle in Poland.

    PubMed

    Polak, Mirosław P; Kuta, Aleksandra; Rybałtowski, Wiesław; Rola, Jerzy; Larska, Magdalena; Zmudziński, Jan F

    2014-12-01

    This report describes the first identification in Poland of bovine viral diarrhoea virus (BVDV)-2 in a dairy herd where severe clinical disease with losses of young animals was observed. The virus was readily cultivated in cell culture and a phylogenetic analysis of the nucleotide sequences and secondary structures of the viral genomic 5' untranslated region confirmed virus identity. The economic impact of the infection was significant compared to the previously prevalent BVDV-1 infections confirming that this genotype of BVDV can cause severe sickness in affected herds. The use of BVDV-1 vaccine did not prevent the infection with the BVDV-2 genotype.

  8. Identification of focal viral infections by confocal microscopy for subsequent ultrastructural analysis.

    PubMed

    Miller, S E; Levenson, R M; Aldridge, C; Hester, S; Kenan, D J; Howell, D N

    1997-01-01

    A correlative microscopy method for the ultrastructural analysis of focal viral tissue infections is presented. Using a confocal scanning laser microscope, foci of infection are identified in tissue sections prior to embedment; a variety of techniques can be employed for viral detection, including staining with standard histochemical reagents and fluorescently labeled antibodies. Areas of infection identified using confocal microscopy are excised from the tissue sections, embedded, and examined by transmission electron microscopy. Applications of this technique in both diagnostic and basic research settings are described.

  9. Metabolomics technology and their application to the study of the viral infection.

    PubMed

    Noto, Antonio; Dessi, Angelica; Puddu, Melania; Mussap, Michele; Fanos, Vassilios

    2014-10-01

    In the present review article we have summarized the use of the metabolomics approach to study the metabolic modifications occurring in several bio-fluids due to viral infections. The aim is to highlight the ability of metabolomics to find early fingerprints, which are related to the infections. The (1)H-NMR, UHPLC/MS/MS(2), UPLC/ESI-SYNAPT-HDMS, UPLC-Q-TOF-HDMS analyses were used for the determination of several metabolites representative of the viral infections. The data were analyzed by Principal Component Analysis (PCA), Partial Least Square Discriminant Analysis (PLS-DA) and by regression techniques. The major changes were related to nucleotide, carbohydrates, lipids and amino acid metabolisms. The metabolomics approach could be considered a viable option for characterization of the viral infection and for detecting on going differences in the bio-fluids composition.

  10. The effects of exposure of susceptible alpacas to alpacas persistently infected with bovine viral diarrhea virus

    PubMed Central

    Byers, Stacey R.; Evermann, James F.; Bradway, Daniel S.; Grimm, Amanda L.; Ridpath, Julia F.; Parish, Steven M.; Tibary, Ahmed; Barrington, George M.

    2011-01-01

    Reports of bovine viral diarrhea virus (BVDV) infections in alpacas have been increasing in recent years but much is still unknown about the mechanisms of disease in this species. This report characterizes the transmission of BVDV from persistently infected (PI) alpacas to BVDV naïve alpacas, documents shedding patterns, and characterizes the disease effects in both PI and transiently infected alpacas. Two PI alpacas shed BVDV Type 1b virus in most body fluids, and commonly available diagnostic tests verified their status. Bovine viral diarrhea virus Type 1b transient infections produced only mild signs of disease in BVDV naïve alpacas. Viremia was detected in whole blood, but viral shedding during the acute phase was not detected and antibody appeared to be protective upon re-exposure to the virus. PMID:21629418

  11. [An epidemiological study of herpetic viral infections in the Republic of Byelarus].

    PubMed

    Kolomiets, A G; Savitskaia, T V; Matveev, V A; Mel'nichenko, E M; Zhukovskiĭ, V G; Luk'ianenko, I G; Sebut, N S; Ospovat, Ia M; Kolomiets, N D

    1997-01-01

    Studies on the epidemiology of infections caused by Herpes simplex virus, cytomegalovirus and Epstein-Barr virus in different age groups of the population of the Republic of Belarus, carried out over the period of many years, are summarized. The frequency of clinical manifestations of different forms of herpetic viral pathology in newborns, children and adults in different regions of the republic was studied. More frequent cases of the most severe clinical forms of herpetic viral infections (encephalitides, generalized infection) were noted in persons having immunodeficient states of different etiology, as well as among the population residing on the territory with unfavorable radiation conditions as a consequence of the catastrophe in the Chernobyl nuclear electric power station. For further study of the specific features of the epidemiology of herpetic obligatory registration of all cases of herpetic viral infections, starting from January 1, 1996, was introduced.

  12. Neural dysfunction following respiratory viral infection as a cause of chronic cough hypersensitivity.

    PubMed

    Undem, Bradley J; Zaccone, Eric; McGarvey, Lorcan; Mazzone, Stuart B

    2015-08-01

    Respiratory viral infections are a common cause of acute coughing, an irritating symptom for the patient and an important mechanism of transmission for the virus. Although poorly described, the inflammatory consequences of infection likely induce coughing by chemical (inflammatory mediator) or mechanical (mucous) activation of the cough-evoking sensory nerves that innervate the airway wall. For some individuals, acute cough can evolve into a chronic condition, in which cough and aberrant airway sensations long outlast the initial viral infection. This suggests that some viruses have the capacity to induce persistent plasticity in the neural pathways mediating cough. In this brief review we present the clinical evidence of acute and chronic neural dysfunction following viral respiratory tract infections and explore possible mechanisms by which the nervous system may undergo activation, sensitization and plasticity.

  13. HBV/HCV dual infection impacts viral load, antibody response, and cytokine expression differently from HBV or HCV single infection

    PubMed Central

    Chen, Fei; Zhang, Jian; Wen, Bo; Luo, Shan; Lin, Yingbiao; Ou, Wensheng; Guo, Fengfan; Tang, Ping; Liu, Wenpei; Qu, Xiaowang

    2016-01-01

    Hepatitis B virus/hepatitis C virus (HBV/HCV) dual infection is common among high-risk individuals. To characterize the virological and immunological features of patients with HBV/HCV dual infection, we enrolled 1,049 individuals who have been identified as injection drug users. Patients were divided into single and dual infection groups according to the serological markers. We found the average HCV RNA level was significantly lower; however, HBV viral load was significantly higher in HBV/HCV dual-infected patients (n = 42) comparing HCV single infection (n = 340) or HBV single infection (n = 136). The level of anti-HBs in patients who experienced spontaneous HBV clearance was higher than that in HCV single-infected patients with HBV spontaneous clearance. The level of anti-HCV E2 in HBV/HCV dual infection was lower than that detected in HCV single infection. Serum levels of IL-6, IL-8, and TNF-α were significantly lower in HBV/HCV dual-infected patients than in patients infected with HBV or HCV alone. Taken together, two viral replications are imbalanced in dual infected patients. The anti-HBs and anti-HCV E2 antibody production were impaired and proinflammatory IL-6, IL-8, and TNF-α also downregulated due to dual infection. These findings will help further understanding the pathogenesis of HBV/HCV dual infection. PMID:28009018

  14. Differential infection patterns of CD4+ T cells and lymphoid tissue viral burden distinguish progressive and nonprogressive lentiviral infections

    PubMed Central

    Vinton, Carol; Tabb, Brian; Hao, Xing Pei; Connick, Elizabeth; Paiardini, Mirko; Lifson, Jeffrey D.; Silvestri, Guido

    2012-01-01

    Nonhuman primate natural hosts for simian immunodeficiency viruses (SIV) develop a nonresolving chronic infection but do not develop AIDS. Mechanisms to explain the nonprogressive nature of SIV infection in natural hosts that underlie maintained high levels of plasma viremia without apparent loss of target cells remain unclear. Here we used comprehensive approaches (ie, FACS sorting, quantitative RT-PCR, immunohistochemistry, and in situ hybridization) to study viral infection within subsets of peripheral blood and lymphoid tissue (LT) CD4+ T cells in cohorts of chronically SIV-infected rhesus macaques (RMs), HIV-infected humans, and SIVsmm-infected sooty mangabeys (SMs). We find: (1) infection frequencies among CD4+ T cells in chronically SIV-infected RMs are significantly higher than those in SIVsmm-infected SMs; (2) infected cells are found in distinct anatomic LT niches and different CD4+ T-cell subsets in SIV-infected RMs and SMs, with infection patterns of RMs reflecting HIV infection in humans; (3) TFH cells are infected at higher frequencies in RMs and humans than in SMs; and (4) LT viral burden, including follicular dendritic cell deposition of virus, is increased in RMs and humans compared with SMs. These data provide insights into how natural hosts are able to maintain high levels of plasma viremia while avoiding development of immunodeficiency. PMID:22990012

  15. Tick-borne flavivirus infection in Ixodes scapularis larvae: development of a novel method for synchronous viral infection of ticks

    PubMed Central

    Mitzel, Dana N.; Wolfinbarger, James B.; Daniel Long, R.; Masnick, Max; Best, Sonja M.; Bloom, Marshall E.

    2007-01-01

    Following a bite from an infected tick, tick-borne flaviviruses cause encephalitis, meningitis and hemorrhagic fever in humans. Although these viruses spend most of their time in the tick, little is known regarding the virus-vector interactions. We developed a simple method for synchronously infecting Ixodes scapularis larvae with Langat virus (LGTV) by immersion in media containing the virus. This technique resulted in approximately 96% of ticks becoming infected. LGTV infection and replication were demonstrated by both viral antigen expression and the accumulation of viral RNA. Furthermore, ticks transmitted LGTV to 100% of the mice and maintained the virus through molting into the next life stage. This technique circumvents limitations present in the current methods by mimicking the natural route of infection and by using attenuated virus strains to infect ticks; thereby, making this technique a powerful tool to study both virus and tick determinants of replication, pathogenesis and transmission. PMID:17490700

  16. Tick-borne flavivirus infection in Ixodes scapularis larvae: development of a novel method for synchronous viral infection of ticks.

    PubMed

    Mitzel, Dana N; Wolfinbarger, James B; Long, R Daniel; Masnick, Max; Best, Sonja M; Bloom, Marshall E

    2007-09-01

    Following a bite from an infected tick, tick-borne flaviviruses cause encephalitis, meningitis and hemorrhagic fever in humans. Although these viruses spend most of their time in the tick, little is known regarding the virus-vector interactions. We developed a simple method for synchronously infecting Ixodes scapularis larvae with Langat virus (LGTV) by immersion in media containing the virus. This technique resulted in approximately 96% of ticks becoming infected. LGTV infection and replication were demonstrated by both viral antigen expression and the accumulation of viral RNA. Furthermore, ticks transmitted LGTV to 100% of the mice and maintained the virus through molting into the next life stage. This technique circumvents limitations present in the current methods by mimicking the natural route of infection and by using attenuated virus strains to infect ticks, thereby making this technique a powerful tool to study both virus and tick determinants of replication, pathogenesis and transmission.

  17. A host-based RT-PCR gene expression signature to identify acute respiratory viral infection.

    PubMed

    Zaas, Aimee K; Burke, Thomas; Chen, Minhua; McClain, Micah; Nicholson, Bradly; Veldman, Timothy; Tsalik, Ephraim L; Fowler, Vance; Rivers, Emanuel P; Otero, Ronny; Kingsmore, Stephen F; Voora, Deepak; Lucas, Joseph; Hero, Alfred O; Carin, Lawrence; Woods, Christopher W; Ginsburg, Geoffrey S

    2013-09-18

    Improved ways to diagnose acute respiratory viral infections could decrease inappropriate antibacterial use and serve as a vital triage mechanism in the event of a potential viral pandemic. Measurement of the host response to infection is an alternative to pathogen-based diagnostic testing and may improve diagnostic accuracy. We have developed a host-based assay with a reverse transcription polymerase chain reaction (RT-PCR) TaqMan low-density array (TLDA) platform for classifying respiratory viral infection. We developed the assay using two cohorts experimentally infected with influenza A H3N2/Wisconsin or influenza A H1N1/Brisbane, and validated the assay in a sample of adults presenting to the emergency department with fever (n = 102) and in healthy volunteers (n = 41). Peripheral blood RNA samples were obtained from individuals who underwent experimental viral challenge or who presented to the emergency department and had microbiologically proven viral respiratory infection or systemic bacterial infection. The selected gene set on the RT-PCR TLDA assay classified participants with experimentally induced influenza H3N2 and H1N1 infection with 100 and 87% accuracy, respectively. We validated this host gene expression signature in a cohort of 102 individuals arriving at the emergency department. The sensitivity of the RT-PCR test was 89% [95% confidence interval (CI), 72 to 98%], and the specificity was 94% (95% CI, 86 to 99%). These results show that RT-PCR-based detection of a host gene expression signature can classify individuals with respiratory viral infection and sets the stage for prospective evaluation of this diagnostic approach in a clinical setting.

  18. In vivo imaging of alphaherpesvirus infection reveals synchronized activity dependent on axonal sorting of viral proteins.

    PubMed

    Granstedt, Andrea E; Bosse, Jens B; Thiberge, Stephan Y; Enquist, Lynn W

    2013-09-10

    A clinical hallmark of human alphaherpesvirus infections is peripheral pain or itching. Pseudorabies virus (PRV), a broad host range alphaherpesvirus, causes violent pruritus in many different animals, but the mechanism is unknown. Previous in vitro studies have shown that infected, cultured peripheral nervous system (PNS) neurons exhibited aberrant electrical activity after PRV infection due to the action of viral membrane fusion proteins, yet it is unclear if such activity occurs in infected PNS ganglia in living animals and if it correlates with disease symptoms. Using two-photon microscopy, we imaged autonomic ganglia in living mice infected with PRV strains expressing GCaMP3, a genetically encoded calcium indicator, and used the changes in calcium flux to monitor the activity of many neurons simultaneously with single-cell resolution. Infection with virulent PRV caused these PNS neurons to fire synchronously and cyclically in highly correlated patterns among infected neurons. This activity persisted even when we severed the presynaptic axons, showing that infection-induced firing is independent of input from presynaptic brainstem neurons. This activity was not observed after infections with an attenuated PRV recombinant used for circuit tracing or with PRV mutants lacking either viral glycoprotein B, required for membrane fusion, or viral membrane protein Us9, required for sorting virions and viral glycoproteins into axons. We propose that the viral fusion proteins produced by virulent PRV infection induce electrical coupling in unmyelinated axons in vivo. This action would then give rise to the synchronous and cyclical activity in the ganglia and contribute to the characteristic peripheral neuropathy.

  19. Live cell imaging reveals the relocation of dsRNA binding proteins upon viral infection.

    PubMed

    Barton, Deborah; Roovers, Elke; Gouil, Quentin; C da Fonseca, Guilherme; Reis, Rodrigo S; Jackson, Craig; Overall, Robyn; Fusaro, Adriana; Waterhouse, Peter

    2017-03-15

    Viral infection triggers a range of plant responses such as the activation of the RNA interference (RNAi) pathway. The double-stranded RNA binding (DRB) proteins, DRB3 and DRB4, are part of this pathway and aid in defending against DNA and RNA viruses, respectively. Using live cell imaging, we show that DRB2, DRB3 and DRB5 relocate from their uniform cytoplasmic distribution to concentrated accumulation in nascent viral replication complexes (VRCs) that develop following cell invasion by viral RNA. Inactivation of the DRB3 gene in Arabidopsis, by T-DNA insertion, rendered these plants less able to repress RNA viral replication. We propose a model for the early stages of virus defense in which DRB2, DRB3 and DRB5 are invasion sensors that relocate to nascent VRCs, where they bind to viral RNA and inhibit virus replication.

  20. An accurate two-phase approximate solution to the acute viral infection model

    SciTech Connect

    Perelson, Alan S

    2009-01-01

    During an acute viral infection, virus levels rise, reach a peak and then decline. Data and numerical solutions suggest the growth and decay phases are linear on a log scale. While viral dynamic models are typically nonlinear with analytical solutions difficult to obtain, the exponential nature of the solutions suggests approximations can be found. We derive a two-phase approximate solution to the target cell limited influenza model and illustrate the accuracy using data and previously established parameter values of six patients infected with influenza A. For one patient, the subsequent fall in virus concentration was not consistent with our predictions during the decay phase and an alternate approximation is derived. We find expressions for the rate and length of initial viral growth in terms of the parameters, the extent each parameter is involved in viral peaks, and the single parameter responsible for virus decay. We discuss applications of this analysis in antiviral treatments and investigating host and virus heterogeneities.

  1. Viral infection and aging as cofactors for the development of pulmonary fibrosis

    PubMed Central

    Naik, Payal K; Moore, Bethany B

    2011-01-01

    Idiopathic pulmonary fibrosis (IPF) is a disease of unknown origin and progression that primarily affects older adults. Accumulating clinical and experimental evidence suggests that viral infections may play a role, either as agents that predispose the lung to fibrosis or exacerbate existing fibrosis. In particular, herpesviruses have been linked with IPF. This article summarizes the evidence for and against viral cofactors in IPF pathogenesis. In addition, we review mechanistic studies in animal models that highlight the fibrotic potential of viral infection, and explore the different mechanisms that might be responsible. We also review early evidence to suggest that the aged lung may be particularly susceptible to viral-induced fibrosis and make recommendations for future research directions. PMID:21128751

  2. Molecular detection of gastrointestinal viral infections in hospitalized patients.

    PubMed

    Rovida, Francesca; Campanini, Giulia; Piralla, Antonio; Adzasehoun, Kodjo Messan Guy; Sarasini, Antonella; Baldanti, Fausto

    2013-11-01

    Gastrointestinal viral syndromes are a common cause of morbidity and mortality in humans worldwide. Etiological agents include a large number of viruses encompassing several orders, families, and genera. During the period April 2011 to April 2012, 689 stool samples from as many patients hospitalized at the Fondazione IRCCS Policlinico San Matteo of Pavia exhibiting gastrointestinal syndromes were examined for the presence of rotavirus, norovirus, astrovirus, adenovirus, rhinovirus, enterovirus, parechovirus, bocavirus, coronavirus, sapovirus, cosavirus, and aichi virus using polymerase chain reaction assays. Gastrointestinal viral agents were detected in 246 (36%) patients of the 689 analyzed. Adenovirus and norovirus were the most common viruses in this cohort, while aichi virus was the only gastrointestinal agent not detected. Surprisingly, rhinovirus was one of the most frequently detected viruses. However, a potential association with gastroenteritis remains to be confirmed.

  3. Passive immunization against highly pathogenic Avian Influenza Virus (AIV) strain H7N3 with antiserum generated from viral polypeptides protect poultry birds from lethal viral infection.

    PubMed

    Shahzad, Mirza Imran; Naeem, Khalid; Mukhtar, Muhammad; Khanum, Azra

    2008-11-28

    Our studies were aimed at developing a vaccination strategy that could provide protection against highly pathogenic avian influenza virus (AIV), H7N3 or its variants outbreaks. A purified viral stock of highly pathogenic H7N3 isolate was lysed to isolate viral proteins by electrophresing on 12% sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), followed by their elution from gel through trituration in phosphate buffered saline (PBS). Overall, five isolated viral polypeptides/proteins upon characterization were used to prepare hyperimmune monovalent serum against respective polypeptides independently and a mixture of all five in poultry birds, and specificity confirmation of each antiserum through dot blot and Western blotting. Antiserum generated from various group birds was pooled and evaluated in 2-week old broiler chicken, for its protection against viral challenge. To evaluate in-vivo protection of each antiserum against viral challenges, six groups of 2-week old broiler chicken were injected with antiserum and a seventh control group received normal saline. Each group was exposed to purified highly pathogenic AIV H7N3 strain at a dose 10(5) embryo lethal dose (ELD(50)). We observed that nucleoprotein (NP) antiserum significantly protected birds from viral infection induced morbidity, mortality and lowered viral shedding compared with antiserum from individual viral proteins or mixed polypeptides/proteins inclusive of NP component. The capability of individual viral polypeptide specific antisera to protect against viral challenges in decreasing order was nucleoprotein (NP) > hemagglutinin (HA) > neuraminidase (NA) > viral proteins mix > viral polymerase (PM) > non-structural proteins (NS). Our data provide proof of concept for potential utilization of passive immunization in protecting poultry industry during infection outbreaks. Furthermore conserved nature of avian NP makes it an ideal candidate to produce antiserum protective against viral

  4. Asthma: the interplay between viral infections and allergic diseases.

    PubMed

    Rowe, Regina K; Gill, Michelle A

    2015-02-01

    Respiratory viruses and allergens synergistically contribute to disease pathogenesis in asthma. Potential mechanisms underlying this clinically relevant association are the subject of intense investigation. This review summarizes current knowledge and recent advances in this area, with an emphasis on potential mechanisms involving immunoglobulin E, type I interferon antiviral responses, epithelial factors, and the role of dendritic cells and other antigen-presenting cells in linking viral and allergic inflammatory responses relevant to asthmatic disease.

  5. Effect of the bovine viral diarrhoea virus (BVDV) infection on dairy calf rearing.

    PubMed

    Diéguez, Francisco J; Yus, Eduardo; Vilar, María J; Sanjuán, María L; Arnaiz, Ignacio

    2009-08-01

    The aim of this study was to compare the cumulative incidence of mortality, clinical diarrhoea and respiratory disease in calves, during their first six months of age, in herds with different bovine viral diarrhoea virus (BVDV) infection status. Calves' health indicators were tested by comparing proportions in 101 farms with dissimilar infection condition. The results indicate that there was a significant relationship between the BVDV status (actively infected herd or not) and the cumulative incidence of mortality and respiratory disorders.

  6. [Presence of autocomplementary RNA with viral specificity in cells infected with herpes virus].

    PubMed

    Béchet, J M; Montagnier, L; Latarjet, R

    1975-01-13

    RNA from cells infected with Herpes simplex virus contain a higher percentage of double-stranded RNA than non-infected cells. This percentage increases three-fold upon self-annealing. The complementary RNA sequences were shown to be virus-specific by the following criteria: (1) high melting temperature than double-stranded RNA from non infected cells; (2) higher density in caesium sulphate; (3) specific hybridization with viral DNA.

  7. Viral infections transmitted by food of animal origin: the present situation in the European Union.

    PubMed

    Stolle, A; Sperner, B

    1997-01-01

    The goal of this presentation was to clarify which foods are involved in viral diseases, which viruses are transmitted via food and how to evaluate the risk of a foodborne viral infection. Food items frequently identified as cause of viral disease outbreaks were shellfish harvested in sewage-contaminated water. Another common source of foodborne viral illness was cold food contaminated by infected food handlers. In the European Union the viruses most frequently associated with foodborne illness were hepatitis A virus and the SRSV's. A few isolated cases of foodborne hepatitis E were reported in Mediterranean countries. Compared to other foodborne diseases, those caused by viruses are less severe and seldom fatal. This might be a reason why the problem of viral contamination of food has been neglected. Yet, because many foodborne viral diseases are not recognized either as foodborne or as caused by viruses, the actual number of cases must be assumed to be significantly higher than the reported number. Consequently, food associated diseases of viral origin should be granted more attention.

  8. [Imported viral infections in international travel; from the virtual to real epidemiology of pandemics].

    PubMed

    Jänisch, T; Junghanss, T

    2000-07-15

    Viruses have become more mobile alongside with increasing human mobility and speed of travel. At the same time we get access to information on viral outbreaks and epidemics from large parts of the world faster than ever before. Two recent epidemics will be presented to explore the value and the consequences of communicating epidemiological information through the Internet. The epidemiology, clinical features, diagnostic procedures and prophylaxis of imported viral infections are presented. Risk factors for the emergence and resurgence of viral diseases are being discussed.

  9. Twenty years of psychoneuroimmunology and viral infections in Brain, Behavior, and Immunity.

    PubMed

    Bonneau, Robert H; Padgett, David A; Sheridan, John F

    2007-03-01

    For 20 years, Brain, Behavior, and Immunity has provided an important venue for the publication of studies in psychoneuroimmunology. During this time period, psychoneuroimmunology has matured into an important multidisciplinary science that has contributed significantly to our knowledge of mind, brain, and body interactions. This review will not only focus on the primary research papers dealing with psychoneuroimmunology, viral infections, and anti-viral vaccine responses in humans and animal models that have appeared on the pages of Brain, Behavior, and Immunity during the past 20 years, but will also outline a variety of strategies that could be used for expanding our understanding of the neuroimmune-viral pathogen relationship.

  10. Radiometric Methods for Rapid Diagnosis of Viral Infection.

    DTIC Science & Technology

    1975-11-01

    4, 6, 24, 48, and 72 hours postinfection, infection time beginning when the 14C-labeled medium was added. Nucleic acid sT, thesis system. Stationary...coccus epidermidis, Pseudomonas aeruginosa, and Acinetobacter caloaceticus var. anitratus) had no effect on the DNA synthesis of HSV-1 infected or...7 UNCLASS 41 RADIOMETRIC METHODS FOR RAPID DIAGNIS F VIRA ~ /fl INFECTION (U) JOHNS HOPKINS UNIV BALTIMORE MDUNC . IFEDH N WAG ER FT AL. NOV 75

  11. Stimulation of viral infection of bacterioplankton during a mesoscale iron fertilization experiment in the Southern Ocean

    NASA Astrophysics Data System (ADS)

    Weinbauer, M. G.; Arrieta, J.-M.; Herndl, G. J.

    2003-04-01

    A mesoscale iron fertilization in the Southern Ocean (Eisenex ) induced a phytoplankton bloom within three weeks observation as well as in an increased bacterial abundance and production. Viral abundance and viral production were stimulated as well. A virus-dilution approach was used to estimate the frequency of infected cells (FIC) and the frequency of lysogenic cells (FLC), i.e. cells with a dormant viral genome. While the FLC did not vary strongly within the iron-enriched patch and did not differ from waters outside the patch, FIC increased significantly within the iron fertilized patch. This suggests that induction of the lytic cycle in lysogenic cells was not significant. Rather, the stimulated bacterial production and abundance within the patch resulted in higher and more successful encounters between viruses and hosts and thus in higher FIC values. Consequently, the iron fertilization enhanced the influence of viral infection in the microbial food web. According to the current model, this should result a stimulation of bacterial production, since lysed bacterial cells cannot be consumed up by protists and transferred to higher trophic level; lysis products can be taken up by bacteria and thus organic carbon spins within this viral loop. Viral infection is a significant and previously overlooked factor in the carbon flow during iron fertilization experiments.

  12. Inflammation and innate immune response against viral infections in marine fish.

    PubMed

    Novoa, B; Mackenzie, S; Figueras, A

    2010-01-01

    Viral infections in fish are common in both natural and cultured fish populations and the spread of infectious disease is a serious threat to both natural ecosystems and commercial exploitations. A significant body of studies have addressed the host response to viral infection including the efficacy of DNA vaccines however we still have a fragmented vision of both pathologies associated with viral infection and the immune response to those across fish species. Many studies have concentrated upon freshwater fish including the zebrafish (Danio rerio) and the Rainbow trout (Oncorhynchus mykiss) whereas the majority of marine fish studies address the Atlantic salmon (Salmo salar). Here we provide a comprehensive review concentrating upon the salient pathological features of the most common viral infections including examples of the Betanodaviruses, Birnaviruses, Rhabdoviruses and the Isavirus in cultured fish with emphasis where possible upon non-salmonid cold water adapted marine species. In parallel we review the current state of the art mainly in reference to gene expression studies describing the host innate immune response concentrating upon the inflammatory response and its relationship toward anti-viral immunity in fish. Due to the complexity of the observed responses and the limitations of candidate gene expression studies to describe global biological processes, recent efforts in the use of microarray analysis for the study of the anti-viral response have been highlighted including members of the Pleuronectiform and the Perciform families. Finally we review the potential of the zebrafish to become a significant biological model in the elucidation of the molecular mechanisms underlying the piscine immune response to viral infection.

  13. Dengue viral infection monitoring from diagnostic to recovery using Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Firdous, Shamaraz; Anwar, Shahzad

    2015-08-01

    Raman spectroscopy has been found useful for monitoring the dengue patient diagnostic and recovery after infection. In the present work, spectral changes that occurred in the blood sera of a dengue infected patient and their possible utilization for monitoring of infection and recovery were investigated using 532 nm wavelength of light. Raman spectrum peaks for normal and after recovery of dengue infection are observed at 1527, 1170, 1021 cm-1 attributed to guanine, adenine, TRP (protein) carbohydrates peak for solids, and skeletal C-C stretch of lipids acyl chains. Where in the dengue infected patient Raman peaks are at 1467, 1316, 1083, and 860 attributed to CH2/CH3 deformation of lipids and collagen, guanine (B, Z-marker), lipids and protein bands. Due to antibodies and antigen reactions the portions and lipids concentration totally changes in dengue viral infection compared to normal blood. These chemical changes in blood sera of dengue viral infection in human blood may be used as possible markers to indicate successful remission and suggest that Raman spectroscopy may provide a rapid optical method for continuous monitoring or evaluation of a protein bands and an antibodies population. Accumulate acquisition mode was used to reduce noise and thermal fluctuation and improve signal to noise ratio. This in vitro dengue infection monitoring methodology will lead in vivo noninvasive on-line monitoring and screening of viral infected patients and their recovery.

  14. Does Viral Co-Infection Influence the Severity of Acute Respiratory Infection in Children?

    PubMed

    Cebey-López, Miriam; Herberg, Jethro; Pardo-Seco, Jacobo; Gómez-Carballa, Alberto; Martinón-Torres, Nazareth; Salas, Antonio; Martinón-Sánchez, José María; Justicia, Antonio; Rivero-Calle, Irene; Sumner, Edward; Fink, Colin; Martinón-Torres, Federico

    2016-01-01

    Multiple viruses are often detected in children with respiratory infection but the significance of co-infection in pathogenesis, severity and outcome is unclear. To correlate the presence of viral co-infection with clinical phenotype in children admitted with acute respiratory infections (ARI). We collected detailed clinical information on severity for children admitted with ARI as part of a Spanish prospective multicenter study (GENDRES network) between 2011-2013. A nested polymerase chain reaction (PCR) approach was used to detect respiratory viruses in respiratory secretions. Findings were compared to an independent cohort collected in the UK. 204 children were recruited in the main cohort and 97 in the replication cohort. The number of detected viruses did not correlate with any markers of severity. However, bacterial superinfection was associated with increased severity (OR: 4.356; P-value = 0.005), PICU admission (OR: 3.342; P-value = 0.006), higher clinical score (1.988; P-value = 0.002) respiratory support requirement (OR: 7.484; P-value < 0.001) and longer hospital length of stay (OR: 1.468; P-value < 0.001). In addition, pneumococcal vaccination was found to be a protective factor in terms of degree of respiratory distress (OR: 2.917; P-value = 0.035), PICU admission (OR: 0.301; P-value = 0.011), lower clinical score (-1.499; P-value = 0.021) respiratory support requirement (OR: 0.324; P-value = 0.016) and oxygen necessity (OR: 0.328; P-value = 0.001). All these findings were replicated in the UK cohort. The presence of more than one virus in hospitalized children with ARI is very frequent but it does not seem to have a major clinical impact in terms of severity. However bacterial superinfection increases the severity of the disease course. On the contrary, pneumococcal vaccination plays a protective role.

  15. Viral infection triggers rapid differentiation of human blood monocytes into dendritic cells.

    PubMed

    Hou, Wanqiu; Gibbs, James S; Lu, Xiuju; Brooke, Christopher B; Roy, Devika; Modlin, Robert L; Bennink, Jack R; Yewdell, Jonathan W

    2012-03-29

    Surprisingly little is known about the interaction of human blood mononuclear cells with viruses. Here, we show that monocytes are the predominant cell type infected when peripheral blood mononuclear cells are exposed to viruses ex vivo. Remarkably, infection with vesicular stomatitis virus, vaccinia virus, and a variety of influenza A viruses (including circulating swine-origin virus) induces monocytes to differentiate within 18 hours into CD16(-)CD83(+) mature dendritic cells with enhanced capacity to activate T cells. Differentiation into dendritic cells does not require cell division and occurs despite the synthesis of viral proteins, which demonstrates that monocytes counteract the capacity of these highly lytic viruses to hijack host cell biosynthetic capacity. Indeed, differentiation requires infectious virus and viral protein synthesis. These findings demonstrate that monocytes are uniquely susceptible to viral infection among blood mononuclear cells, with the likely purpose of generating cells with enhanced capacity to activate innate and acquired antiviral immunity.

  16. Experimental infection of pigs with the porcine respiratory coronavirus (PRCV): measure of viral excretion.

    PubMed

    Bourgueil, E; Hutet, E; Cariolet, R; Vannier, P

    1992-04-01

    Twelve pigs were experimentally infected with a porcine respiratory coronavirus (PRCV) by the oronasal route. Viral excretion was measured daily by two means-deep nasal swabs and air samples obtained in a cyclone sampler. Clinical signs were very slight on infected pigs. Airborne virus could be recovered from day 1 to day 6 post-infection in the cyclone sampler as well as in petri dishes placed in the same loose-box. Viral titres obtained from nasal swabs were significantly correlated with those obtained from air samples. Different collection media were compared. The most efficient media for the collection of infectious viral particles contained a protective agent such as foetal calf serum.

  17. Methamphetamine mediates immune dysregulation in a murine model of chronic viral infection

    PubMed Central

    Sriram, Uma; Haldar, Bijayesh; Cenna, Jonathan M.; Gofman, Larisa; Potula, Raghava

    2015-01-01

    Methamphetamine (METH) is a highly addictive psychostimulant that not only affects the brain and cognitive functions but also greatly impacts the host immune system, rendering the body susceptible to infections and exacerbating the severity of disease. Although there is gathering evidence about METH abuse and increased incidence of HIV and other viral infections, not much is known about the effects on the immune system in a chronic viral infection setting. We have used the lymphocytic choriomeningitis virus (LCMV) chronic mouse model of viral infection in a chronic METH environment and demonstrate that METH significantly increases CD3 marker on splenocytes and programmed death-1 (PD-1) expression on T cells, a cell surface signaling molecule known to inhibit T cell function and cause exhaustion in a lymphoid organ. Many of these METH effects were more pronounced during early stage of infection, which are gradually attenuated during later stages of infection. An essential cytokine for T-lymphocyte homeostasis, Interleukin-2 (IL-2) in serum was prominently reduced in METH-exposed infected mice. In addition, the serum pro-inflammatory (TNF, IL12 p70, IL1β, IL-6, and KC-GRO) and Th2 (IL-2, IL-10, and IL-4) cytokine profiles were also altered in the presence of METH. Interestingly CXCR3, an inflammatory chemokine receptor, showed significant increase in the METH treated LCMV infected mice. Similarly, compared to only infected mice, epidermal growth factor receptor (EGFR) in METH exposed LCMV infected mice were up regulated. Collectively, our data suggest that METH alters systemic, peripheral immune responses and modulates key markers on T cells involved in pathogenesis of chronic viral infection. PMID:26322025

  18. Evidence for persistent Bovine viral diarrhea virus infection in a captive mountain goat (Oreamnos americanus).

    PubMed

    Nelson, Danielle D; Dark, Michael J; Bradway, Daniel S; Ridpath, Julia F; Call, Neill; Haruna, Julius; Rurangirwa, Fred R; Evermann, James F

    2008-11-01

    Bovine viral diarrhea (BVD) viruses are pestiviruses that have been isolated from domestic and wild ruminants. There is serologic evidence of pestiviral infection in more than 40 species of free-range and captive mammals. Vertical transmission can produce persistently infected animals that are immunotolerant to the infecting strain of Bovine viral diarrhea virus (BVDV) and shed virus throughout their lives. Seven species (white-tailed deer, mouse deer, eland, domestic cattle, alpaca, sheep, and pigs) have been definitively identified as persistently infected with BVDV. This study provides serological, molecular, immunohistochemical, and histological evidence for BVDV infection in 2 captive mountain goats from a zoological park in Idaho. The study was triggered by isolation of BVDV from tissues and immunohistochemical identification of viral antigen within lesions of a 7-month-old male mountain goat (goat 1). Blood was collected from other mountain goats and white-tailed and mule deer on the premises for BVDV serum neutralization, viral isolation, and reverse transcription polymerase chain reaction. One 3-month-old mountain goat (goat 2) was antibody negative and BVDV positive in serum samples collected 3 months apart. This goat subsequently died, and though still antibody negative, BVDV was isolated from tissues and identified by immunohistochemistry within lesions. Sequencing and phylogenetic analysis identified the isolates as BVDV-2. These findings provide evidence of persistent infection in a mountain goat, underscoring the need for pestivirus control strategies for wild ruminants in zoological collections.

  19. Cytotoxic CD4 T Cells—Friend or Foe during Viral Infection?

    PubMed Central

    Juno, Jennifer A.; van Bockel, David; Kent, Stephen J.; Kelleher, Anthony D.; Zaunders, John J.; Munier, C. Mee Ling

    2017-01-01

    CD4 T cells with cytotoxic function were once thought to be an artifact due to long-term in vitro cultures but have in more recent years become accepted and reported in the literature in response to a number of viral infections. In this review, we focus on cytotoxic CD4 T cells in the context of human viral infections and in some infections that affect mice and non-human primates. We examine the effector mechanisms used by cytotoxic CD4 cells, the phenotypes that describe this population, and the transcription factors and pathways that lead to their induction following infection. We further consider the cells that are the predominant targets of this effector subset and describe the viral infections in which CD4 cytotoxic T lymphocytes have been shown to play a protective or pathologic role. Cytotoxic CD4 T cells are detected in the circulation at much higher levels than previously realized and are now recognized to have an important role in the immune response to viral infections. PMID:28167943

  20. Cytotoxic CD4 T Cells-Friend or Foe during Viral Infection?

    PubMed

    Juno, Jennifer A; van Bockel, David; Kent, Stephen J; Kelleher, Anthony D; Zaunders, John J; Munier, C Mee Ling

    2017-01-01

    CD4 T cells with cytotoxic function were once thought to be an artifact due to long-term in vitro cultures but have in more recent years become accepted and reported in the literature in response to a number of viral infections. In this review, we focus on cytotoxic CD4 T cells in the context of human viral infections and in some infections that affect mice and non-human primates. We examine the effector mechanisms used by cytotoxic CD4 cells, the phenotypes that describe this population, and the transcription factors and pathways that lead to their induction following infection. We further consider the cells that are the predominant targets of this effector subset and describe the viral infections in which CD4 cytotoxic T lymphocytes have been shown to play a protective or pathologic role. Cytotoxic CD4 T cells are detected in the circulation at much higher levels than previously realized and are now recognized to have an important role in the immune response to viral infections.

  1. New possible biomarkers for diagnosis of infections and diagnostic distinction between bacterial and viral infections in children.

    PubMed

    Yusa, Takashi; Tateda, Kazuhiro; Ohara, Akira; Miyazaki, Shuichi

    2017-02-01

    Detailed information about patients with infections is required to ensure appropriate choice of treatment. Although white blood cell (WBC) counts, and C-reactive protein (CRP) levels are useful diagnostic indicators of infections, more rapid and easily assayed indicator(s) could improve diagnosis. Moreover, it is of pivotal importance to distinguish bacteria or viruses as causative pathogens. Overall, TLR2 and TLR4 expression levels in neutrophils derived from individuals (n = 118) with bacterial (n = 37) and viral (n = 34) infections were higher than those in control samples (n = 47). Significant higher levels of TNF-α in patients with both types of the infection were observed, and those of IL-4, IL-8, IL-10, and IL-12 also were observed in the present study. Levels of IL-2, IL-8, and IL-10 on day 1 post-viral infection were significantly higher than those on day 1 post-bacterial infection. Therefore, there is a possibility that IL-4, IL-8, IL-10, IL-12 and TNF-α might be biomarkers for infections, in addition to WBC counts and CRP levels, and that IL-2, IL-8 or IL-10 are potentially able to distinguish between bacterial and viral infections. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. Contrasting life strategies of viruses that infect photo- and heterotrophic bacteria, as revealed by viral tagging.

    PubMed

    Deng, Li; Gregory, Ann; Yilmaz, Suzan; Poulos, Bonnie T; Hugenholtz, Philip; Sullivan, Matthew B

    2012-10-30

    Ocean viruses are ubiquitous and abundant and play important roles in global biogeochemical cycles by means of their mortality, horizontal gene transfer, and manipulation of host metabolism. However, the obstacles involved in linking viruses to their hosts in a high-throughput manner bottlenecks our ability to understand virus-host interactions in complex communities. We have developed a method called viral tagging (VT), which combines mixtures of host cells and fluorescent viruses with flow cytometry. We investigated multiple viruses which infect each of two model marine bacteria that represent the slow-growing, photoautotrophic genus Synechococcus (Cyanobacteria) and the fast-growing, heterotrophic genus Pseudoalteromonas (Gammaproteobacteria). Overall, viral tagging results for viral infection were consistent with plaque and liquid infection assays for cyanobacterial myo-, podo- and siphoviruses and some (myo- and podoviruses) but not all (four siphoviruses) heterotrophic bacterial viruses. Virus-tagged Pseudoalteromonas organisms were proportional to the added viruses under varied infection conditions (virus-bacterium ratios), while no more than 50% of the Synechococcus organisms were virus tagged even at viral abundances that exceeded (5 to 10×) that of their hosts. Further, we found that host growth phase minimally impacts the fraction of virus-tagged Synechococcus organisms while greatly affecting phage adsorption to Pseudoalteromonas. Together these findings suggest that at least two contrasting viral life strategies exist in the oceans and that they likely reflect adaptation to their host microbes. Looking forward to the point at which the virus-tagging signature is well understood (e.g., for Synechococcus), application to natural communities should begin to provide population genomic data at the proper scale for predictively modeling two of the most abundant biological entities on Earth. Viral study suffers from an inability to link viruses to hosts en

  3. Viral Protein Kinetics of Piscine Orthoreovirus Infection in Atlantic Salmon Blood Cells

    PubMed Central

    Haatveit, Hanne Merethe; Wessel, Øystein; Markussen, Turhan; Lund, Morten; Thiede, Bernd; Nyman, Ingvild Berg; Braaen, Stine; Dahle, Maria Krudtaa; Rimstad, Espen

    2017-01-01

    Piscine orthoreovirus (PRV) is ubiquitous in farmed Atlantic salmon (Salmo salar) and the cause of heart and skeletal muscle inflammation. Erythrocytes are important target cells for PRV. We have investigated the kinetics of PRV infection in salmon blood cells. The findings indicate that PRV causes an acute infection of blood cells lasting 1–2 weeks, before it subsides into persistence. A high production of viral proteins occurred initially in the acute phase which significantly correlated with antiviral gene transcription. Globular viral factories organized by the non-structural protein µNS were also observed initially, but were not evident at later stages. Interactions between µNS and the PRV structural proteins λ1, µ1, σ1 and σ3 were demonstrated. Different size variants of µNS and the outer capsid protein µ1 appeared at specific time points during infection. Maximal viral protein load was observed five weeks post cohabitant challenge and was undetectable from seven weeks post challenge. In contrast, viral RNA at a high level could be detected throughout the eight-week trial. A proteolytic cleavage fragment of the µ1 protein was the only viral protein detectable after seven weeks post challenge, indicating that this µ1 fragment may be involved in the mechanisms of persistent infection. PMID:28335455

  4. Viral Protein Kinetics of Piscine Orthoreovirus Infection in Atlantic Salmon Blood Cells.

    PubMed

    Haatveit, Hanne Merethe; Wessel, Øystein; Markussen, Turhan; Lund, Morten; Thiede, Bernd; Nyman, Ingvild Berg; Braaen, Stine; Dahle, Maria Krudtaa; Rimstad, Espen

    2017-03-18

    Piscine orthoreovirus (PRV) is ubiquitous in farmed Atlantic salmon (Salmo salar) and the cause of heart and skeletal muscle inflammation. Erythrocytes are important target cells for PRV. We have investigated the kinetics of PRV infection in salmon blood cells. The findings indicate that PRV causes an acute infection of blood cells lasting 1-2 weeks, before it subsides into persistence. A high production of viral proteins occurred initially in the acute phase which significantly correlated with antiviral gene transcription. Globular viral factories organized by the non-structural protein µNS were also observed initially, but were not evident at later stages. Interactions between µNS and the PRV structural proteins λ1, µ1, σ1 and σ3 were demonstrated. Different size variants of µNS and the outer capsid protein µ1 appeared at specific time points during infection. Maximal viral protein load was observed five weeks post cohabitant challenge and was undetectable from seven weeks post challenge. In contrast, viral RNA at a high level could be detected throughout the eight-week trial. A proteolytic cleavage fragment of the µ1 protein was the only viral protein detectable after seven weeks post challenge, indicating that this µ1 fragment may be involved in the mechanisms of persistent infection.

  5. Evidence of restricted viral replication in adult mink infected with Aleutian disease of mink parvovirus.

    PubMed Central

    Alexandersen, S; Bloom, M E; Wolfinbarger, J

    1988-01-01

    Strand-specific hybridization probes were used in in situ molecular hybridization specifically to localize cells containing replicative intermediates of Aleutian disease of mink parvovirus (ADV). When adult mink of Aleutian genotype were infected with ADV Utah I, the largest number of cells positive for viral replication (i.e., containing replicative-form DNA and RNA) were found in the mesenteric lymph nodes and spleens at 10 days after infection. The localization of positive cells in the middle of germinal centers suggested that they were B lymphoblasts. Circulating leukocytes and bone marrow cells also contained viral RNA, but the levels of replicative-form DNA were below detectability. The levels of viral DNA and RNA in adult mink cells replicating ADV were decreased compared with those in permissively infected cell cultures or neonatal mink, suggesting that the replication of ADV in adult mink might be semipermissive or restricted at some early stage of viral gene expression. The low level of viral replication and transcription in lymphoid cells might provide a mechanism for the development of immune disorders and for the maintenance of persistent infection. Single-stranded virion DNA was found in other organs, but the strand-specific probes made it possible to show that this DNA represented virus sequestration. In addition, glomerular immune complexes containing virion DNA were detected, suggesting that ADV virions, or perhaps free DNA, may have a role in the development of ADV-induced glomerulonephritis. Images PMID:2833604

  6. A tightly regulated IL-22 response maintains immune functions and homeostasis in systemic viral infection.

    PubMed

    Yi, Panpan; Liang, Yuejin; Yuan, Denley Ming Kee; Jie, Zuliang; Kwota, Zakari; Chen, Yan; Cong, Yingzi; Fan, Xuegong; Sun, Jiaren

    2017-06-20

    Interleukin-22 (IL-22) plays an important role in host immunity and tissue homeostasis in infectious and inflammatory diseases. However, the function and regulation of IL-22 in viral infection remain largely unknown. Here, we report that viral infection triggered early IL-22 production from the liver and lymphoid organs. γδ T cells are the main immune cells to produce IL-22 in the liver, a process mediated by the IL-23/phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin complex 1 (mTORC1) signaling pathway. In the presence of IL-23, IL-22 production is independent of aryl hydrocarbon receptor (AhR) signaling. In acute and persistent viral infections, IL-22 deficiency resulted in thymic and splenic hypertrophy, while excessive IL-22 induced atrophy in these lymphoid organs. Moreover, IL-22 deficiency enhanced T cell responses to promote viral clearance, but increased IL-22 in vivo decreased T cell numbers and functions in the liver and lymphoid tissues. Together, our findings reveal a significant effect of the IL-23/PI3K/mTORC1 axis on regulating IL-22 production and also identify a novel role of IL-22 in controlling antiviral T cell responses in the non-lymphoid and lymphoid organs during acute and persistent viral infections.

  7. Combined genetic and epigenetic interferences with interferon signaling expose prostate cancer cells to viral infection

    PubMed Central

    Sabo, Yosef; Bacharach, Eran; Ehrlich, Marcelo

    2016-01-01

    Interferons (IFNs) induce anti-viral programs, regulate immune responses, and exert anti-proliferative effects. To escape anti-tumorigenic effects of IFNs, malignant cells attenuate JAK/STAT signaling and expression of IFN stimulated genes (ISGs). Such attenuation may enhance the susceptibility of tumor cells to oncolytic virotherapy. Here we studied genetic and epigenetic mechanisms of interference with JAK/STAT signaling and their contribution to susceptibility of prostate cancer cells to viral infection. Bioinformatics analysis of gene-expression in cohorts of prostate cancer patients revealed genetic and epigenetic interference with the IFN program. To correlate lack of IFN signaling and susceptibility to viral infection and oncolysis; we employed LNCaP prostate cancer cells as cellular model, and the human metapneumovirus and the epizootic hemorrhagic disease virus as infectious agents. In LNCaP cells, JAK1 is silenced by bi-allelic inactivating mutations and epigenetic silencing, which also silences ISGs. Chemical inhibition of epigenetic silencing partially restored IFN-sensitivity, induced low levels of expression of selected ISGs and attenuated, but failed to block, viral infection and oncolysis. Since viral infection was not blocked by epigenetic modifiers, and these compounds may independently-induce anti-tumor effects, we propose that epigenetic modifiers and virotherapy are compatible in treatment of prostate tumors defective in JAK1 expression and IFN signaling. PMID:27366948

  8. Mobilizing monocytes to cross-present circulating viral antigen in chronic infection

    PubMed Central

    Gehring, Adam J.; Haniffa, Muzlifah; Kennedy, Patrick T.; Ho, Zi Zong; Boni, Carolina; Shin, Amanda; Banu, Nasirah; Chia, Adeline; Lim, Seng Gee; Ferrari, Carlo; Ginhoux, Florent; Bertoletti, Antonio

    2013-01-01

    Selection of antigens for therapeutic vaccination against chronic viral infections is complicated by pathogen genetic variations. We tested whether antigens present during persistent viral infections could provide a personalized antigenic reservoir for therapeutic T cell expansion in humans. We focused our study on the HBV surface antigen (HBsAg), which is present in microgram quantities in the serum of chronic HBV patients. We demonstrated by quantitative fluorescent microscopy that, out of 6 professional APC populations in the circulation, only CD14 monocytes (MNs) retained an HBsAg depot. Using TCR-redirected CD8+ T cells specific for MHC-I–restricted HBV epitopes, we showed that, despite being constantly exposed to antigen, ex vivo–isolated APCs did not constitutively activate HBV-specific CD8+ T cells. However, differentiation of HBsAg+ CD14 MNs from chronic patients to MN-derived DCs (moDCs) induced cross-presentation of the intracellular reservoir of viral antigen. We exploited this mechanism to cross-present circulating viral antigen and showed that moDCs from chronically infected patients stimulated expansion of autologous HBV-specific T cells. Thus, these data demonstrate that circulating viral antigen produced during chronic infection can serve as a personalized antigenic reservoir to activate virus-specific T cells. PMID:23908113

  9. Sphingosine Kinase 1 Serves as a Pro-Viral Factor by Regulating Viral RNA Synthesis and Nuclear Export of Viral Ribonucleoprotein Complex upon Influenza Virus Infection

    PubMed Central

    Seo, Young-Jin; Pritzl, Curtis J.; Vijayan, Madhuvanthi; Bomb, Kavita; McClain, Mariah E.; Alexander, Stephen; Hahm, Bumsuk

    2013-01-01

    Influenza continues to pose a threat to humans by causing significant morbidity and mortality. Thus, it is imperative to investigate mechanisms by which influenza virus manipulates the function of host factors and cellular signal pathways. In this study, we demonstrate that influenza virus increases the expression and activation of sphingosine kinase (SK) 1, which in turn regulates diverse cellular signaling pathways. Inhibition of SK suppressed virus-induced NF-κB activation and markedly reduced the synthesis of viral RNAs and proteins. Further, SK blockade interfered with activation of Ran-binding protein 3 (RanBP3), a cofactor of chromosome region maintenance 1 (CRM1), to inhibit CRM1-mediated nuclear export of the influenza viral ribonucleoprotein complex. In support of this observation, SK inhibition altered the phosphorylation of ERK, p90RSK, and AKT, which is the upstream signal of RanBP3/CRM1 activation. Collectively, these results indicate that SK is a key pro-viral factor regulating multiple cellular signal pathways triggered by influenza virus infection. PMID:24137500

  10. Complexities in Isolation and Purification of Multiple Viruses from Mixed Viral Infections: Viral Interference, Persistence and Exclusion.

    PubMed

    Kumar, Naveen; Barua, Sanjay; Riyesh, Thachamvally; Chaubey, Kundan K; Rawat, Krishan Dutt; Khandelwal, Nitin; Mishra, Anil K; Sharma, Nitika; Chandel, Surender S; Sharma, Shalini; Singh, Manoj K; Sharma, Dinesh K; Singh, Shoor V; Tripathi, Bhupendra N

    2016-01-01

    Successful purification of multiple viruses from mixed infections remains a challenge. In this study, we investigated peste des petits ruminants virus (PPRV) and foot-and-mouth disease virus (FMDV) mixed infection in goats. Rather than in a single cell type, cytopathic effect (CPE) of the virus was observed in cocultured Vero/BHK-21 cells at 6th blind passage (BP). PPRV, but not FMDV could be purified from the virus mixture by plaque assay. Viral RNA (mixture) transfection in BHK-21 cells produced FMDV but not PPRV virions, a strategy which we have successfully employed for the first time to eliminate the negative-stranded RNA virus from the virus mixture. FMDV phenotypes, such as replication competent but noncytolytic, cytolytic but defective in plaque formation and, cytolytic but defective in both plaque formation and standard FMDV genome were observed respectively, at passage level BP8, BP15 and BP19 and hence complicated virus isolation in the cell culture system. Mixed infection was not found to induce any significant antigenic and genetic diversity in both PPRV and FMDV. Further, we for the first time demonstrated the viral interference between PPRV and FMDV. Prior transfection of PPRV RNA, but not Newcastle disease virus (NDV) and rotavirus RNA resulted in reduced FMDV replication in BHK-21 cells suggesting that the PPRV RNA-induced interference was specifically directed against FMDV. On long-term coinfection of some acute pathogenic viruses (all possible combinations of PPRV, FMDV, NDV and buffalopox virus) in Vero cells, in most cases, one of the coinfecting viruses was excluded at passage level 5 suggesting that the long-term coinfection may modify viral persistence. To the best of our knowledge, this is the first documented evidence describing a natural mixed infection of FMDV and PPRV. The study not only provides simple and reliable methodologies for isolation and purification of two epidemiologically and economically important groups of viruses, but

  11. Complexities in Isolation and Purification of Multiple Viruses from Mixed Viral Infections: Viral Interference, Persistence and Exclusion

    PubMed Central

    Kumar, Naveen; Barua, Sanjay; Riyesh, Thachamvally; Chaubey, Kundan K.; Rawat, Krishan Dutt; Khandelwal, Nitin; Mishra, Anil K.; Sharma, Nitika; Chandel, Surender S.; Sharma, Shalini; Singh, Manoj K.; Sharma, Dinesh K.; Singh, Shoor V.; Tripathi, Bhupendra N.

    2016-01-01

    Successful purification of multiple viruses from mixed infections remains a challenge. In this study, we investigated peste des petits ruminants virus (PPRV) and foot-and-mouth disease virus (FMDV) mixed infection in goats. Rather than in a single cell type, cytopathic effect (CPE) of the virus was observed in cocultured Vero/BHK-21 cells at 6th blind passage (BP). PPRV, but not FMDV could be purified from the virus mixture by plaque assay. Viral RNA (mixture) transfection in BHK-21 cells produced FMDV but not PPRV virions, a strategy which we have successfully employed for the first time to eliminate the negative-stranded RNA virus from the virus mixture. FMDV phenotypes, such as replication competent but noncytolytic, cytolytic but defective in plaque formation and, cytolytic but defective in both plaque formation and standard FMDV genome were observed respectively, at passage level BP8, BP15 and BP19 and hence complicated virus isolation in the cell culture system. Mixed infection was not found to induce any significant antigenic and genetic diversity in both PPRV and FMDV. Further, we for the first time demonstrated the viral interference between PPRV and FMDV. Prior transfection of PPRV RNA, but not Newcastle disease virus (NDV) and rotavirus RNA resulted in reduced FMDV replication in BHK-21 cells suggesting that the PPRV RNA-induced interference was specifically directed against FMDV. On long-term coinfection of some acute pathogenic viruses (all possible combinations of PPRV, FMDV, NDV and buffalopox virus) in Vero cells, in most cases, one of the coinfecting viruses was excluded at passage level 5 suggesting that the long-term coinfection may modify viral persistence. To the best of our knowledge, this is the first documented evidence describing a natural mixed infection of FMDV and PPRV. The study not only provides simple and reliable methodologies for isolation and purification of two epidemiologically and economically important groups of viruses, but

  12. Host Transcriptional Response to Influenza and Other Acute Respiratory Viral Infections--A Prospective Cohort Study.

    PubMed

    Zhai, Yijie; Franco, Luis M; Atmar, Robert L; Quarles, John M; Arden, Nancy; Bucasas, Kristine L; Wells, Janet M; Niño, Diane; Wang, Xueqing; Zapata, Gladys E; Shaw, Chad A; Belmont, John W; Couch, Robert B

    2015-06-01

    To better understand the systemic response to naturally acquired acute respiratory viral infections, we prospectively enrolled 1610 healthy adults in 2009 and 2010. Of these, 142 subjects were followed for detailed evaluation of acute viral respiratory illness. We examined peripheral blood gene expression at 7 timepoints: enrollment, 5 illness visits and the end of each year of the study. 133 completed all study visits and yielded technically adequate peripheral blood microarray gene expression data. Seventy-three (55%) had an influenza virus infection, 64 influenza A and 9 influenza B. The remaining subjects had a rhinovirus infection (N = 32), other viral infections (N = 4), or no viral agent identified (N = 24). The results, which were replicated between two seasons, showed a dramatic upregulation of interferon pathway and innate immunity genes. This persisted for 2-4 days. The data show a recovery phase at days 4 and 6 with differentially expressed transcripts implicated in cell proliferation and repair. By day 21 the gene expression pattern was indistinguishable from baseline (enrollment). Influenza virus infection induced a higher magnitude and longer duration of the shared expression signature of illness compared to the other viral infections. Using lineage and activation state-specific transcripts to produce cell composition scores, patterns of B and T lymphocyte depressions accompanied by a major activation of NK cells were detected in the acute phase of illness. The data also demonstrate multiple dynamic gene modules that are reorganized and strengthened following infection. Finally, we examined pre- and post-infection anti-influenza antibody titers defining novel gene expression correlates.

  13. Host Transcriptional Response to Influenza and Other Acute Respiratory Viral Infections – A Prospective Cohort Study

    PubMed Central

    Zhai, Yijie; Franco, Luis M.; Atmar, Robert L.; Quarles, John M.; Arden, Nancy; Bucasas, Kristine L.; Wells, Janet M.; Niño, Diane; Wang, Xueqing; Zapata, Gladys E.; Shaw, Chad A.; Belmont, John W.; Couch, Robert B.

    2015-01-01

    To better understand the systemic response to naturally acquired acute respiratory viral infections, we prospectively enrolled 1610 healthy adults in 2009 and 2010. Of these, 142 subjects were followed for detailed evaluation of acute viral respiratory illness. We examined peripheral blood gene expression at 7 timepoints: enrollment, 5 illness visits and the end of each year of the study. 133 completed all study visits and yielded technically adequate peripheral blood microarray gene expression data. Seventy-three (55%) had an influenza virus infection, 64 influenza A and 9 influenza B. The remaining subjects had a rhinovirus infection (N = 32), other viral infections (N = 4), or no viral agent identified (N = 24). The results, which were replicated between two seasons, showed a dramatic upregulation of interferon pathway and innate immunity genes. This persisted for 2-4 days. The data show a recovery phase at days 4 and 6 with differentially expressed transcripts implicated in cell proliferation and repair. By day 21 the gene expression pattern was indistinguishable from baseline (enrollment). Influenza virus infection induced a higher magnitude and longer duration of the shared expression signature of illness compared to the other viral infections. Using lineage and activation state-specific transcripts to produce cell composition scores, patterns of B and T lymphocyte depressions accompanied by a major activation of NK cells were detected in the acute phase of illness. The data also demonstrate multiple dynamic gene modules that are reorganized and strengthened following infection. Finally, we examined pre- and post-infection anti-influenza antibody titers defining novel gene expression correlates. PMID:26070066

  14. Final Technical Report: Viral Infection of Subsurface Microorganisms and Metal/Radionuclide Transport

    SciTech Connect

    Weber, Karrie A.; Bender, Kelly S.; Li, Yusong

    2013-09-28

    Microbially mediated metabolisms have been identified as a significant factor either directly or indirectly impacting the fate and transport of heavy metal/radionuclide contaminants. To date microorganisms have been isolated from contaminated environments. Examination of annotated finished genome sequences of many of these subsurface isolates from DOE sites, revealed evidence of prior viral infection. To date the role that viruses play influencing microbial mortality and the resulting community structure which directly influences biogeochemical cycling in soils and sedimentary environments remains poorly understood. The objective of this exploratory study was to investigate the role of viral infection of subsurface bacteria and the formation of contaminant-bearing viral particles. This objective was approached by examining the following working hypotheses: (i) subsurface microorganisms are susceptible to viral infections by the indigenous subsurface viral community, and (ii) viral surfaces will adsorb heavy metals and radionuclides. Our results have addressed basic research needed to accomplish the BER Long Term Measure to provide sufficient scientific understanding such that DOE sites would be able to incorporate coupled physical, chemical and biological processes into decision making for environmental remediation or natural attenuation and long-term stewardship by establishing viral-microbial relationships on the subsequent fate and transport of heavy metals and radionuclides. Here we demonstrated that viruses play a significant role in microbial mortality and community structure in terrestrial subsurface sedimentary systems. The production of viral-like particles within subsurface sediments in response to biostimulation with dissolved organic carbon and a terminal electron acceptor resulted in the production of viral-like particles. Organic carbon alone did not result in significant viral production and required the addition of a terminal electron acceptor

  15. Tissue distribution of bovine viral diarrhea virus antigens in persistently infected cattle.

    PubMed

    Shin, T; Acland, H

    2001-08-01

    The tissue distribution and cellular localization of viral antigens in three cattle with persistent bovine viral diarrhea virus (BVDV) infection was studied. In three cases, necropsy findings of oral ulcers, abmasal ulcers and necrosis of Peyer's patches were suspected have been caused by BVDV infection. Non-cytopathic BVDV was isolated from a tissue pool of liver, kidneys and spleen. Immunohistochemical detection of BVDV showed that BVDV antigens were detected in both epithelial and nonepithelial cells in all examined organs, including the gastrointestinal tract, liver, pancreas, lung, lymphatic organs (spleen, lymph nodes), adrenal gland, ovary, uterus, and the mammary gland. These findings support the hypothesis that animals with persistent BVDV infection spread BVDV through all routes, and that infertility in BVDV infection is associated with the infection of BVDV in the ovaries and uteri.

  16. Long-range transport and universality classes in in vitro viral infection spread

    NASA Astrophysics Data System (ADS)

    Manrubia, S. C.; García-Arriaza, J.; Domingo, E.; Escarmís, C.

    2006-05-01

    Dispersal mechanisms play a main role in the dynamics of infection spread. Recent experimental results with in vitro infections of foot-and-mouth disease virus reveal that the time needed for the virus to kill a cellular monolayer depends qualitatively on the number of viral particles required to initiate infection in a susceptible cell. A two-dimensional susceptible-infected-removed (SIR) model based on the experimental setting agrees with the observations only when viral particles are subject to long-range transport. Numerical and analytical results show that this long-range transport plays a role when a single particle causes infection, while it is inefficient when complementation between two or more particles is necessary.

  17. Influence of viral infection on essential oil composition of Ocimum basilicum (Lamiaceae).

    PubMed

    Nagai, Alice; Duarte, Ligia M L; Santos, Déborah Y A C

    2011-08-01

    Ocimum basilicum L., popularly known as sweet basil, is a Lamiaceae species whose essential oil is mainly composed of monoterpenes, sesquiterpenes and phenylpropanoids. The contents of these compounds can be affected by abiotic and biotic factors such as infections caused by viruses. The main goal of this research was an investigation of the effects of viral infection on the essential oil profile of common basil. Seeds of O. basilicum L. cv. Genovese were sowed and kept in a greenhouse. Plants presenting two pairs of leaves above the cotyledons were inoculated with an unidentified virus isolated from a field plant showing chlorotic yellow spots and foliar deformation. Essential oils of healthy and infected plants were extracted by hydrodistillation and analyzed by GCMS. Changes in essential oil composition due to viral infection were observed. Methyleugenol and p-cresol,2,6-di-tert-butyl were the main constituents. However, methyleugenol contents were significantly decreased in infected plants.

  18. dsRNA sensing during viral infection: lessons from plants, worms, insects, and mammals.

    PubMed

    de Faria, Isaque João da Silva; Olmo, Roenick Proveti; Silva, Emanuele Guimarães; Marques, João Trindade

    2013-05-01

    Host defense systems often rely on direct and indirect pattern recognition to sense the presence of invading pathogens. Patterns can be molecules directly produced by the pathogen or indirectly generated by changes in host parameters as a consequence of infection. Viruses are intracellular pathogens that hijack the cellular machinery to synthesize their own molecules making direct recognition of viral molecules a great challenge. Antiviral systems in prokaryotes and eukaryotes commonly exploit aberrant nucleic acid sensing to recognize virus infection as host and viral nucleic acid metabolism can greatly differ. Indeed, the generation of dsRNA is often associated with viral infection. In this review, we discuss current knowledge on the mechanisms of viral dsRNA sensing utilized by 2 important antiviral defense systems, RNA interference (RNAi) and the vertebrate immune system. The major viral sensors of the vertebrate immune systems are RIG-like receptors, while RNAi pathways depend on Dicer proteins. These 2 families of sensors share a similar helicase domain with high specificity for dsRNA, which is necessary, but not sufficient for efficient recognition by these receptors. Additional intrinsic features to the dsRNA molecule are also necessary for activation of antiviral systems. Studies utilizing synthetic ligands, in vitro biochemistry and reporter systems have greatly helped increase our knowledge on intrinsic features of dsRNA recognition. However, characteristics such as subcellular localization are extrinsic to the dsRNA itself, but certainly influence the recognition in vivo. Thus, mechanisms of viral dsRNA recognition must address how cellular sensors are recruited to nucleic acids or vice versa. Accessory proteins are likely important for in vivo recognition of extrinsic features of viral RNA, but have mostly remained undiscovered due to the limitations of previous strategies. Hence, the identification of novel components of antiviral systems must take

  19. Viral Infection Is Not Uncommon in Adult Patients with Severe Hospital-Acquired Pneumonia

    PubMed Central

    Hong, Hyo-Lim; Hong, Sang-Bum; Ko, Gwang-Beom; Huh, Jin Won; Sung, Heungsup; Do, Kyung-Hyun; Kim, Sung-Han; Lee, Sang-Oh; Kim, Mi-Na; Jeong, Jin-Yong; Lim, Chae-Man; Kim, Yang Soo; Woo, Jun Hee; Koh, Younsuck; Choi, Sang-Ho

    2014-01-01

    Background Viral pathogens have not generally been regarded as important causes of severe hospital-acquired pneumonia (HAP), except in patients with hematologic malignancy or transplant recipients. We investigated the role and distribution of viruses in adult with severe HAP who required intensive care. Methods From March 2010 to February 2012, adult patients with severe HAP required admission to the intensive care unit (ICU), 28-bed medical ICU in a tertiary care hospital, were prospectively enrolled. Respiratory viruses were detected using multiplex reverse-transcription polymerase chain reaction and/or shell vial culture. Results A total of 262 patients were enrolled and 107 patients (40.8%) underwent bronchoscopic BAL for etiologic diagnosis. One hundred and fifty-six patients (59.5%) had bacterial infections and 59 patients (22.5%) had viral infections. Viruses were detected in BAL fluid specimens of 37 patients (62.7%, 37/59). The most commonly identified viruses were respiratory syncytial virus and parainfluenza virus (both 27.1%, 16/59), followed by rhinovirus (25.4%, 15/59), and influenza virus (16.9%, 10/59). Twenty-one patients (8.0%, 21/262) had bacterial-viral coinfections and Staphylococcus aureus was the most commonly coexisting bacteria (n = 10). Viral infection in non-immunocompromised patients was not uncommon (11.1%, 16/143), although it was not as frequent as that in immunocompromised patients (36.4%, 43/119). Non-immunocompromised patients were significantly older than immunocompromised patients and had significantly higher rates of underlying chronic obstructive pulmonary disease, tuberculous destroyed lung and chronic kidney disease. The 28 day mortalities of patients with bacterial infections, viral infections and bacterial-viral coinfections were not significantly different (29.5%, 35.6% and 19.0%, respectively; p = 0.321). Conclusions Viral pathogens are not uncommon in adult patients with severe HAP who required ICU admission

  20. Exhaustion of type I interferon response following an acute viral infection.

    PubMed

    Alsharifi, Mohammed; Regner, Matthias; Blanden, Robert; Lobigs, Mario; Lee, Eva; Koskinen, Aulikki; Müllbacher, Arno

    2006-09-01

    Viral infections often cause a period of heightened susceptibility to a secondary infection but the cause of this phenomenon is unknown. We found that a primary viral infection in mice rapidly triggers an IFN-I-dependent partial activation state in the majority of B and T lymphocytes, which reverts to a resting phenotype within 5 days. When a secondary infection with an unrelated virus occurred 5 to 9 days after the primary infection, no recurrence of marked activation of lymphocytes was observed. This was not due to an inherent inability of the previously activated cells to undergo renewed partial activation, because they responded when challenged with virus after transfer into "naive" recipients. Instead, the failure to respond optimally resided in the original host's incapacity to mount an IFN-I response to the secondary infection during this time period. Thus, transient immunosuppression through exhaustion of IFN-I production during an acute viral infection creates a time period of enhanced susceptibility to secondary infection.

  1. Viral kinetics and exhaled droplet size affect indoor transmission dynamics of influenza infection.

    PubMed

    Chen, S C; Chio, C P; Jou, L J; Liao, C M

    2009-10-01

    The purpose of this paper was to investigate the effects of viral kinetics and exhaled droplet size on indoor transmission dynamics of influenza infection. The target cell-limited model with delayed virus production was adopted to strengthen the inner mechanisms of virus infection on human epithelial cell. The particle number and volume involved in the viral kinetics were linked with Wells-Riley mathematical equation to quantify the infection risk. We investigated population dynamics in a specific elementary school by using the seasonal susceptible - exposed - infected - recovery (SEIR) model. We found that exhaled pulmonary bioaerosol of sneeze (particle diameter <10 microm) have 10(2)-fold estimate higher than that of cough. Sneeze and cough caused risk probabilities range from 0.075 to 0.30 and 0.076, respectively; whereas basic reproduction numbers (R(0)) estimates range from 4 to 17 for sneeze and nearly 4 for cough, indicating sneeze-posed higher infection risk. The viral kinetics and exhaled droplet size for sneeze affect indoor transmission dynamics of influenza infection since date post-infection 1-7. This study provides direct mechanistic support that indoor influenza virus transmission can be characterized by viral kinetics in human upper respiratory tracts that are modulated by exhaled droplet size. Practical Implications This paper provides a predictive model that can integrate the influenza viral kinetics (target cell-limited model), indoor aerosol transmission potential (Wells-Riley mathematical equation), and population dynamic model [susceptible - exposed - infected - recovery (SEIR) model] in a proposed susceptible population. Viral kinetics expresses the competed results of human immunity ability with influenza virus generation. By linking the viral kinetics and different exposure parameters and environmental factors in a proposed school setting with five age groups, the influenza infection risk can be estimated. On the other hand, we implicated

  2. Strain Variation and Disease Severity in Congenital Cytomegalovirus Infection: In Search of a Viral Marker.

    PubMed

    Arav-Boger, Ravit

    2015-09-01

    The wide spectrum of congenital cytomegalovirus (CMV) disease and known differences in the biology and in vitro growth of CMV strains continue to drive studies in search for specific viral genetic determinants that may predict severity of congenital CMV disease. Several CMV genes have been studied in detail in congenitally infected children, but the complexity of the viral genome and differences in the definition of symptomatic disease versus asymptomatic CMV infection continue to raise questions related to what constitutes a pathogenic CMV strain. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Viral RNA at Two Stages of Reovirus Infection Is Required for the Induction of Necroptosis.

    PubMed

    Berger, Angela K; Hiller, Bradley E; Thete, Deepti; Snyder, Anthony J; Perez, Encarnacion; Upton, Jason W; Danthi, Pranav

    2017-03-15

    Necroptosis, a regulated form of necrotic cell death, requires the activation of the RIP3 kinase. Here, we identify that infection of host cells with reovirus can result in necroptosis. We find that necroptosis requires sensing of the genomic RNA within incoming virus particles via cytoplasmic RNA sensors to produce type I interferon (IFN). While these events that occur prior to the de novo synthesis of viral RNA are required for the induction of necroptosis, they are not sufficient. The induction of necroptosis also requires late stages of reovirus infection. Specifically, efficient synthesis of double-stranded RNA (dsRNA) within infected cells is required for necroptosis. These data indicate that viral RNA interfaces with host components at two different stages of infection to induce necroptosis. This work provides new molecular details about events in the viral replication cycle that contribute to the induction of necroptosis following infection with an RNA virus.IMPORTANCE An appreciation of how cell death pathways are regulated following viral infection may reveal strategies to limit tissue destruction and prevent the onset of disease. Cell death following virus infection can occur by apoptosis or a regulated form of necrosis known as necroptosis. Apoptotic cells are typically disposed of without activating the immune system. In contrast, necroptotic cells alert the immune system, resulting in inflammation and tissue damage. While apoptosis following virus infection has been extensively investigated, how necroptosis is unleashed following virus infection is understood for only a small group of viruses. Here, using mammalian reovirus, we highlight the molecular mechanism by which infection with a dsRNA virus results in necroptosis.

  4. The control of bovine viral diarrhoea virus infection.

    PubMed

    Harkness, J W

    1987-01-01

    In this paper, current ideas concerning the epidemiology of BVD virus infection are reviewed briefly, together with its possible economic implications. The different types of control strategies are considered. Problems associated with vaccination are discussed.

  5. Dendritic cell-mediated HIV-1 infection of T-cells demonstrates a direct relationship to plasma viral RNA levels

    PubMed Central

    Arora, Reetakshi; Bull, Lara; Siwak, Edward B.; Thippeshappa, Rajesh; Arduino, Roberto C.; Kimata, Jason T.

    2011-01-01

    Objective To examine the relationship between infectivity of HIV-1 variants in dendritic cell-mediated in trans infection of T-cells and plasma viral RNA levels in infected subjects. Methods HIV-1 was isolated from PBMCs of chronically infected individuals, typed for coreceptor usage, and viral replication was examined in monocyte derived-dendritic cells-peripheral blood lymphocytes (DC-PBL) co-cultures. The rate of p24 antigen production during the logarithmic phase of viral replication was determined by ELISA. Additionally, nef variants were cloned and expressed in trans with a HIV-luciferase vector and CCR5-tropic HIV-1 envelope, and infectivity was measured in DC-mediated capture-transfer assays. Results Replication capacity of HIV-1 viral CCR5-tropic isolates in DC-PBL co-cultures was linearly associated with the plasma viral RNA levels in a cohort of HIV-1 infected individuals exhibiting an inverse relationship between plasma viral RNA and CD4 cell count. Furthermore, infectivity activity of Nef variants in context of DC-mediated enhanced infection of T-cells also showed a linear relationship to plasma viral RNA levels. Conclusion These results illustrate that replication capacity of HIV-1 in DC-T-cell cultures is a significant predictor of plasma viral RNA level. The data suggest that adaptation of HIV-1 to DC interactions with T-cells influences the level of viral replication in the host. PMID:20386455

  6. High Serum Lipopolysaccharide-Binding Protein Level in Chronic Hepatitis C Viral Infection Is Reduced by Anti-Viral Treatments

    PubMed Central

    Nien, Hsiao-Ching; Hsu, Shih-Jer; Su, Tung-Hung; Yang, Po-Jen; Sheu, Jin-Chuan; Wang, Jin-Town; Chow, Lu-Ping; Chen, Chi-Ling

    2017-01-01

    Background Lipopolysaccharide-binding protein (LBP) has been reported to associate with metabolic diseases, such as obesity, diabetes, and non-alcoholic fatty liver disease. Since chronic hepatitis C virus (HCV) infection is associated with metabolic derangements, the relationship between LBP and HCV deserves additional studies. This study aimed to determine the serum LBP level in subjects with or without HCV infection and investigate the change of its level after anti-viral treatments with or without interferon. Methods and Findings We recruited 120 non-HCV subjects, 42 and 17 HCV-infected subjects respectively treated with peginterferon α-2a/ribavirin and direct-acting antiviral drugs. Basic information, clinical data, serum LBP level and abdominal ultrasonography were collected. All the subjects provided written informed consent before being enrolled approved by the Research Ethics Committee of the National Taiwan University Hospital. Serum LBP level was significantly higher in HCV-infected subjects than non-HCV subjects (31.0 ± 8.8 versus 20.0 ± 6.4 μg/mL; p-value < 0.001). After multivariate analyses, LBP at baseline was independently associated with body mass index, hemoglobin A1c, alanine aminotransferase (ALT) and HCV infection. Moreover, the baseline LBP was only significantly positively associated with ALT and inversely with fatty liver in HCV-infected subjects. The LBP level significantly decreased at sustained virologic response (27.4 ± 6.6 versus 34.6 ± 7.3 μg/mL, p-value < 0.001; 15.9 ± 4.4 versus 22.2 ± 5.7 μg/mL, p-value = 0.001), regardless of interferon-based or -free therapy. Conclusions LBP, an endotoxemia associated protein might be used as an inflammatory biomarker of both infectious and non-infectious origins in HCV-infected subjects. PMID:28107471

  7. Fatal hepatitis E viral infection in pregnant women in Ghana: a case series

    PubMed Central

    2012-01-01

    Background Viral infections during pregnancy can pose serious threats to mother and fetus from the time of conception to the time of delivery. These lead to congenital defects, spontaneous abortion and even death. The definitive diagnosis and management of pregnancy-related viral infections may be challenging especially in less resourced countries. Case presentation We present clinical and laboratory responses to the diagnosis and management of three cases of fulminant hepatitis secondary to Hepatitis E viral infection in pregnancy. Case 1 was a 31-year-old Ghanaian woman who presented with a week’s history of passing dark urine as well as yellowish discoloration of the eyes. She subsequently developed fulminant hepatitis secondary to Hepatitis E viral infection, spontaneously aborted at 24 weeks of gestation and later died. Case 2 was also a 31-year-old Ghanaian woman who was admitted with a four-day history of jaundice. She had low grade fever, but no history of abdominal pain, haematuria, pale stool or pruritus. She next developed fulminant hepatitis secondary to Hepatitis E viral infection. However, she did not miscarry but died at 28 weeks of gestation. Case 3 was a 17-year-old Ghanaian woman who was referred to the tertiary health facility on account of jaundice and anaemia. She had delivered a live male infant at maturity of 32 weeks but noticed she was jaundiced and had a presentation of active disease 3 days prior to delivery. The baby was icteric at birth and on evaluation, had elevated bilirubin (mixed type) with normal liver enzymes. Hepatitis E virus infection was confirmed in both mother and baby. However, the jaundice and the hepatomegaly resolved in mother and baby after 5 and 12 days respectively. Conclusion To the best of our knowledge, these are the first documented cases of fatal fulminant hepatic failures resulting from HEV infection in Ghana. PMID:22937872

  8. Liver Monocytes and Kupffer Cells Remain Transcriptionally Distinct during Chronic Viral Infection

    PubMed Central

    van de Garde, Martijn D. B.; Movita, Dowty; van der Heide, Marieke; Herschke, Florence; De Jonghe, Sandra; Gama, Lucio; Boonstra, Andre

    2016-01-01

    Due to the scarcity of immunocompetent animal models for chronic viral hepatitis, little is known about the role of the innate intrahepatic immune system during viral replication in the liver. These insights are however fundamental for the understanding of the inappropriate adaptive immune responses during the chronic phase of the infection. We apply the Lymphocytic Choriomenigitis Virus (LCMV) clone 13 mouse model to examine chronic virus-host interactions of Kupffer cells (KC) and infiltrating monocytes (IM) in an infected liver. LCMV infection induced overt clinical hepatitis, with rise in ALT and serum cytokines, and increased intrahepatic F4/80 expression. Despite ongoing viral replication, whole liver transcriptome showed baseline expression levels of inflammatory cytokines, interferons, and interferon induced genes during the chronic infection phase. Transcriptome analyses of sorted KC and IMs using NanoString technology revealed two unique phenotypes with only minimal overlap. At the chronic viral infection phase, KC showed no increased transcription of activation markers Cd80 and Cd86, but an increased expression of genes related to antigen presentation, whereas monocytes were more activated and expressed higher levels of Tnf transcripts. Although both KCs and intrahepatic IM share the surface markers F4/80 and CD11b, their transcriptomes point towards distinctive roles during virus-induced chronic hepatitis. PMID:27812182

  9. Respiratory viral infections in children with asthma: do they matter and can we prevent them?

    PubMed Central

    2012-01-01

    Background Asthma is a major public health problem with a huge social and economic burden affecting 300 million people worldwide. Viral respiratory infections are the major cause of acute asthma exacerbations and may contribute to asthma inception in high risk young children with susceptible genetic background. Acute exacerbations are associated with decreased lung growth or accelerated loss of lung function and, as such, add substantially to both the cost and morbidity associated with asthma. Discussion While the importance of preventing viral infection is well established, preventive strategies have not been well explored. Good personal hygiene, hand-washing and avoidance of cigarette smoke are likely to reduce respiratory viral infections. Eating a healthy balanced diet, active probiotic supplements and bacterial-derived products, such as OM-85, may reduce recurrent infections in susceptible children. There are no practical anti-viral therapies currently available that are suitable for widespread use. Summary Hand hygiene is the best measure to prevent the common cold. A healthy balanced diet, active probiotic supplements and immunostimulant OM-85 may reduce recurrent infections in asthmatic children. PMID:22974166

  10. Cullin4 Is Pro-Viral during West Nile Virus Infection of Culex Mosquitoes

    PubMed Central

    Paradkar, Prasad N.; Duchemin, Jean-Bernard; Rodriguez-Andres, Julio; Trinidad, Lee; Walker, Peter J.

    2015-01-01

    Although mosquitoes serve as vectors of many pathogens of public health importance, their response to viral infection is poorly understood. It also remains to be investigated whether viruses deploy some mechanism to be able to overcome this immune response. Here, we have used an RNA-Seq approach to identify differentially regulated genes in Culex quinquefasciatus cells following West Nile virus (WNV) infection, identifying 265 transcripts from various cellular pathways that were either upregulated or downregulated. Ubiquitin-proteasomal pathway genes, comprising 12% of total differentially regulated genes, were selected for further validation by real time RT-qPCR and functional analysis. It was found that treatment of infected cells with proteasomal inhibitor, MG-132, decreased WNV titers, indicating importance of this pathway during infection process. In infection models, the Culex ortholog of mammalian Cul4A/B (cullin RING ubiquitin ligase) was found to be upregulated in vitro as well as in vivo, especially in midguts of mosquitoes. Gene knockdown using dsRNA and overexpression studies indicated that Culex Cul4 acts as a pro-viral protein by degradation of CxSTAT via ubiquitin-proteasomal pathway. We also show that gene knockdown of Culex Cul4 leads to activation of the Jak-STAT pathway in mosquitoes leading to decrease viral replication in the body as well as saliva. Our results suggest a novel mechanism adopted by WNV to overcome mosquito immune response and increase viral replication. PMID:26325027

  11. Cleavage of spike protein of SARS coronavirus by protease factor Xa is associated with viral infectivity

    SciTech Connect

    Du, Lanying; Kao, Richard Y.; Zhou, Yusen; He, Yuxian; Zhao, Guangyu; Wong, Charlotte; Jiang, Shibo; Yuen, Kwok-Yung; Jin, Dong-Yan; Zheng, Bo-Jian . E-mail: bzheng@hkucc.hku.hk

    2007-07-20

    The spike (S) protein of SARS coronavirus (SARS-CoV) has been known to recognize and bind to host receptors, whose conformational changes then facilitate fusion between the viral envelope and host cell membrane, leading to viral entry into target cells. However, other functions of SARS-CoV S protein such as proteolytic cleavage and its implications to viral infection are incompletely understood. In this study, we demonstrated that the infection of SARS-CoV and a pseudovirus bearing the S protein of SARS-CoV was inhibited by a protease inhibitor Ben-HCl. Also, the protease Factor Xa, a target of Ben-HCl abundantly expressed in infected cells, was able to cleave the recombinant and pseudoviral S protein into S1 and S2 subunits, and the cleavage was inhibited by Ben-HCl. Furthermore, this cleavage correlated with the infectivity of the pseudovirus. Taken together, our study suggests a plausible mechanism by which SARS-CoV cleaves its S protein to facilitate viral infection.

  12. P53-Mediated Rapid Induction of Apoptosis Conveys Resistance to Viral Infection in Drosophila melanogaster

    PubMed Central

    Liu, Bo; Behura, Susanta K.; Clem, Rollie J.; Schneemann, Anette; Becnel, James; Severson, David W.; Zhou, Lei

    2013-01-01

    Arthropod-borne pathogens account for millions of deaths each year. Understanding the genetic mechanisms controlling vector susceptibility to pathogens has profound implications for developing novel strategies for controlling insect-transmitted infectious diseases. The fact that many viruses carry genes that have anti-apoptotic activity has long led to the hypothesis that induction of apoptosis could be a fundamental innate immune response. However, the cellular mechanisms mediating the induction of apoptosis following viral infection remained enigmatic, which has prevented experimental verification of the functional significance of apoptosis in limiting viral infection in insects. In addition, studies with cultured insect cells have shown that there is sometimes a lack of apoptosis, or the pro-apoptotic response happens relatively late, thus casting doubt on the functional significance of apoptosis as an innate immunity. Using in vivo mosquito models and the native route of infection, we found that there is a rapid induction of reaper-like pro-apoptotic genes within a few hours following exposure to DNA or RNA viruses. Recapitulating a similar response in Drosophila, we found that this rapid induction of apoptosis requires the function of P53 and is mediated by a stress–responsive regulatory region upstream of reaper. More importantly, we showed that the rapid induction of apoptosis is responsible for preventing the expression of viral genes and blocking the infection. Genetic changes influencing this rapid induction of reaper-like pro-apoptotic genes led to significant differences in susceptibility to viral infection. PMID:23408884

  13. Impact of Viral Infections on Hematopoiesis: From Beneficial to Detrimental Effects on Bone Marrow Output

    PubMed Central

    Pascutti, Maria Fernanda; Erkelens, Martje N.; Nolte, Martijn A.

    2016-01-01

    The ability of the bone marrow (BM) to generate copious amounts of blood cells required on a daily basis depends on a highly orchestrated process of proliferation and differentiation of hematopoietic stem and progenitor cells (HSPCs). This process can be rapidly adapted under stress conditions, such as infections, to meet the specific cellular needs of the immune response and the ensuing physiological changes. This requires a tight regulation in order to prevent either hematopoietic failure or transformation. Although adaptation to bacterial infections or systemic inflammation has been studied and reviewed in depth, specific alterations of hematopoiesis to viral infections have received less attention so far. Viruses constantly pose a significant health risk and demand an adequate, balanced response from our immune system, which also affects the BM. In fact, both the virus itself and the ensuing immune response can have a tremendous impact on the hematopoietic process. On one hand, this can be beneficial: it helps to boost the cellular response of the body to resolve the viral infection. But on the other hand, when the virus and the resulting antiviral response persist, the inflammatory feedback to the hematopoietic system will become chronic, which can be detrimental for a balanced BM output. Chronic viral infections frequently have clinical manifestations at the level of blood cell formation, and we summarize which viruses can lead to BM pathologies, like aplastic anemia, pancytopenia, hemophagocytic lymphohistiocytosis, lymphoproliferative disorders, and malignancies. Regarding the underlying mechanisms, we address specific effects of acute and chronic viral infections on blood cell production. As such, we distinguish four different levels in which this can occur: (1) direct viral infection of HSPCs, (2) viral recognition by HSPCs, (3) indirect effects on HSPCs by inflammatory mediators, and (4) the role of the BM microenvironment on hematopoiesis upon virus

  14. [WASTE WATERS AS THE RESERVOIR OF INTESTINAL ENTERIC VIRAL INFECTIONS].

    PubMed

    Nedachin, A E; Dmitrieva, R A; Doskina, T V; Dolgin, V A; Chulanov, V P; Pimenov, N N

    2015-01-01

    In the paper there are presented data of field observations of the spectrum of viruses, contained in the waste waters. The studies were performed on the territory of the city and the territory unfavorable for hepatitis A. In the territory of the big city by RT-PCR in the waste liquid the enterovirus RNA was detected in 45% of samples; astroviruses--90%; noroviruses--80% and 15% of rotaviruses. Samples from 2 wells were slightly positive for the presence of HCV RNA A. In the waste liquid on the territory, unfavorable for viral hepatitis A, in 100% of the samples there were determined noro- and astroviruses RNA and adenovirus DNA, in 75%--enterovirus RNA; 50%--HAV RNA and a 25%--rotavirus RNA.

  15. Healthcare-associated viral and bacterial infections in dentistry

    PubMed Central

    Laheij, A.M.G.A.; Kistler, J.O.; Belibasakis, G.N.; Välimaa, H.; de Soet, J.J.

    2012-01-01

    Infection prevention in dentistry is an important topic that has gained more interest in recent years and guidelines for the prevention of cross-transmission are common practice in many countries. However, little is known about the real risks of cross-transmission, specifically in the dental healthcare setting. This paper evaluated the literature to determine the risk of cross-transmission and infection of viruses and bacteria that are of particular relevance in the dental practice environment. Facts from the literature on HSV, VZV, HIV, Hepatitis B, C and D viruses, Mycobacterium spp., Pseudomonas spp., Legionella spp. and multi-resistant bacteria are presented. There is evidence that Hepatitis B virus is a real threat for cross-infection in dentistry. Data for the transmission of, and infection with, other viruses or bacteria in dental practice are scarce. However, a number of cases are probably not acknowledged by patients, healthcare workers and authorities. Furthermore, cross-transmission in dentistry is under-reported in the literature. For the above reasons, the real risks of cross-transmission are likely to be higher. There is therefore a need for prospective longitudinal research in this area, to determine the real risks of cross-infection in dentistry. This will assist the adoption of effective hygiene procedures in dental practice. PMID:22701774

  16. Respiratory tract viral infections in bone marrow transplant patients.

    PubMed

    Raboni, Sonia M; Nogueira, Meri B; Tsuchiya, Luine R V; Takahashi, Gislene A; Pereira, Luciane A; Pasquini, Ricardo; Siqueira, Marilda M

    2003-07-15

    Community respiratory viruses such as respiratory syncytial virus (RSV), adenovirus, influenza A, influenza B, and the parainfluenza group are frequent causes of respiratory disease in bone marrow transplant (BMT) patients. During the period from March 1993 to August 1999, 810 samples of respiratory secretions, nasopharyngeal aspirate (NPA) or bronchoalveolar lavage (BAL), from 722 patients with upper respiratory infections symptoms at the BMT unit of the Federal University in the state of Paraná, Brazil were evaluated for respiratory virus infection. One hundred thirty-six (17%) samples were reactive in 62 patients. RSV was found in 30 of 62 (48%), influenza A in 14 of 62 (23%), influenza B in 9 of 62 (15%), parainfluenza group in 7 of 62 (11%), and adenovirus in 2 of 62 (3%) infected patients. The most frequent clinical manifestations were cough and fever. Pneumonia occurred in 19 of 62 (31%) cases. The mortality rate was 23 of 62 (37%), being higher among patients infected with adenovirus and influenza A. Infections in BMT patients occurred during the outbreak period of these viruses in the community, highlighting the need to establish surveillance measures in units with immunocompromised patients in addition to the development of sensitive and rapid diagnostic tests for the detection of these viruses in patients with respiratory symptoms.

  17. Epidemiology and aetiology of maternal bacterial and viral infections in low- and middle-income countries

    PubMed Central

    Velu, Prasad Palani; Gravett, Courtney A.; Roberts, Tom K.; Wagner, Thor A.; Zhang, Jian Shayne F.; Rubens, Craig E.; Gravett, Michael G.; Campbell, Harry; Rudan, Igor

    2011-01-01

    Background Maternal morbidity and mortality in low- and middle-income countries has remained exceedingly high. However, information on bacterial and viral maternal infections, which are important contributors to poor pregnancy outcomes, is sparse and poorly characterised. This review aims to describe the epidemiology and aetiology of bacterial and viral maternal infections in low- and middle-income countries. Methods A systematic search of published literature was conducted and data on aetiology and epidemiology of maternal infections was extracted from relevant studies for analysis. Searches were conducted in parallel by two reviewers (using OVID) in the following databases: Medline (1950 to 2010), EMBASE (1980 to 2010) and Global Health (1973 to 2010). Results Data from 158 relevant studies was used to characterise the epidemiology of the 10 most extensively reported maternal infections with the following median prevalence rates: Treponema pallidum (2.6%), Neisseria gonorrhoeae (1.5%), Chlamydia trachomatis (5.8%), Group B Streptococcus (8.6%), bacterial vaginosis (20.9%), hepatitis B virus (4.3%), hepatitis C virus (1.4%), Cytomegalovirus (95.7% past infection), Rubella (8.9% susceptible) and Herpes simplex (20.7%). Large variations in the prevalence of these infections between countries and regions were noted. Conclusion This review confirms the suspected high prevalence of maternal bacterial and viral infections and identifies particular diseases and regions requiring urgent attention in public health policy planning, setting research priorities and donor funding towards reducing maternal morbidity and mortality in low- and middle-income countries. PMID:23198117

  18. PAR-1 contributes to the innate immune response during viral infection

    PubMed Central

    Antoniak, Silvio; Owens, A. Phillip; Baunacke, Martin; Williams, Julie C.; Lee, Rebecca D.; Weithäuser, Alice; Sheridan, Patricia A.; Malz, Ronny; Luyendyk, James P.; Esserman, Denise A.; Trejo, JoAnn; Kirchhofer, Daniel; Blaxall, Burns C.; Pawlinski, Rafal; Beck, Melinda A.; Rauch, Ursula; Mackman, Nigel

    2013-01-01

    Coagulation is a host defense system that limits the spread of pathogens. Coagulation proteases, such as thrombin, also activate cells by cleaving PARs. In this study, we analyzed the role of PAR-1 in coxsackievirus B3–induced (CVB3-induced) myocarditis and influenza A infection. CVB3-infected Par1–/– mice expressed reduced levels of IFN-β and CXCL10 during the early phase of infection compared with Par1+/+ mice that resulted in higher viral loads and cardiac injury at day 8 after infection. Inhibition of either tissue factor or thrombin in WT mice also significantly increased CVB3 levels in the heart and cardiac injury compared with controls. BM transplantation experiments demonstrated that PAR-1 in nonhematopoietic cells protected mice from CVB3 infection. Transgenic mice overexpressing PAR-1 in cardiomyocytes had reduced CVB3-induced myocarditis. We found that cooperative signaling between PAR-1 and TLR3 in mouse cardiac fibroblasts enhanced activation of p38 and induction of IFN-β and CXCL10 expression. Par1–/– mice also had decreased CXCL10 expression and increased viral levels in the lung after influenza A infection compared with Par1+/+ mice. Our results indicate that the tissue factor/thrombin/PAR-1 pathway enhances IFN-β expression and contributes to the innate immune response during single-stranded RNA viral infection. PMID:23391721

  19. Actin-binding Protein Drebrin Regulates HIV-1-triggered Actin Polymerization and Viral Infection*

    PubMed Central

    Gordón-Alonso, Mónica; Rocha-Perugini, Vera; Álvarez, Susana; Ursa, Ángeles; Izquierdo-Useros, Nuria; Martinez-Picado, Javier; Muñoz-Fernández, María A.; Sánchez-Madrid, Francisco

    2013-01-01

    HIV-1 contact with target cells triggers F-actin rearrangements that are essential for several steps of the viral cycle. Successful HIV entry into CD4+ T cells requires actin reorganization induced by the interaction of the cellular receptor/co-receptor complex CD4/CXCR4 with the viral envelope complex gp120/gp41 (Env). In this report, we analyze the role of the actin modulator drebrin in HIV-1 viral infection and cell to cell fusion. We show that drebrin associates with CXCR4 before and during HIV infection. Drebrin is actively recruited toward cell-virus and Env-driven cell to cell contacts. After viral internalization, drebrin clustering is retained in a fraction of the internalized particles. Through a combination of RNAi-based inhibition of endogenous drebrin and GFP-tagged expression of wild-type and mutant forms, we establish drebrin as a negative regulator of HIV entry and HIV-mediated cell fusion. Down-regulation of drebrin expression promotes HIV-1 entry, decreases F-actin polymerization, and enhances profilin local accumulation in response to HIV-1. These data underscore the negative role of drebrin in HIV infection by modulating viral entry, mainly through the control of actin cytoskeleton polymerization in response to HIV-1. PMID:23926103

  20. DNA methyltransferase DNMT3A associates with viral proteins and impacts HSV-1 infection.

    PubMed

    Rowles, Daniell L; Tsai, Yuan-Chin; Greco, Todd M; Lin, Aaron E; Li, Minghao; Yeh, Justin; Cristea, Ileana M

    2015-06-01

    Viral infections can alter the cellular epigenetic landscape, through modulation of either DNA methylation profiles or chromatin remodeling enzymes and histone modifications. These changes can act to promote viral replication or host defense. Herpes simplex virus type 1 (HSV-1) is a prominent human pathogen, which relies on interactions with host factors for efficient replication and spread. Nevertheless, the knowledge regarding its modulation of epigenetic factors remains limited. Here, we used fluorescently-labeled viruses in conjunction with immunoaffinity purification and MS to study virus-virus and virus-host protein interactions during HSV-1 infection in primary human fibroblasts. We identified interactions among viral capsid and tegument proteins, detecting phosphorylation of the capsid protein VP26 at sites within its UL37-binding domain, and an acetylation within the major capsid protein VP5. Interestingly, we found a nuclear association between viral capsid proteins and the de novo DNA methyltransferase DNA (cytosine-5)-methyltransferase 3A (DNMT3A), which we confirmed by reciprocal isolations and microscopy. We show that drug-induced inhibition of DNA methyltransferase activity, as well as siRNA- and shRNA-mediated DNMT3A knockdowns trigger reductions in virus titers. Altogether, our results highlight a functional association of viral proteins with the mammalian DNA methyltransferase machinery, pointing to DNMT3A as a host factor required for effective HSV-1 infection.

  1. Viral RNA Degradation and Diffusion Act as a Bottleneck for the Influenza A Virus Infection Efficiency

    PubMed Central

    Jolmes, Fabian; Welke, Robert-William; Klipp, Edda; Herrmann, Andreas; Flöttmann, Max

    2016-01-01

    After endocytic uptake, influenza viruses transit early endosomal compartments and eventually reach late endosomes. There, the viral glycoprotein hemagglutinin (HA) triggers fusion between endosomal and viral membrane, a critical step that leads to release of the viral segmented genome destined to reach the cell nucleus. Endosomal maturation is a complex process involving acidification of the endosomal lumen as well as endosome motility along microtubules. While the pH drop is clearly critical for the conformational change and membrane fusion activity of HA, the effect of intracellular transport dynamics on the progress of infection remains largely unclear. In this study, we developed a comprehensive mathematical model accounting for the first steps of influenza virus infection. We calibrated our model with experimental data and challenged its predictions using recombinant viruses with altered pH sensitivity of HA. We identified the time point of virus-endosome fusion and thereby the diffusion distance of the released viral genome to the nucleus as a critical bottleneck for efficient virus infection. Further, we concluded and supported experimentally that the viral RNA is subjected to cytosolic degradation strongly limiting the probability of a successful genome import into the nucleus. PMID:27780209

  2. Influence of Viral Envelope on Newcastle Disease Virus Infection1

    PubMed Central

    Young, Nancy P.; Ash, Ronald J.

    1974-01-01

    The adsorption characteristics of Newcastle disease virus (NDV) propagated in chicken cells (NDV-C) and in human cells (NDV-H) were examined. Adsorption experiments performed at different temperatures indicated that virus propagated in a particular cell infected that cell type more readily than did virus propagated in a different host. For example, NDV-C was more efficient in initiating infection of chicken cells at 22 C than was NDV-H; the reverse was true when human cells were employed. The results indicate that infection of susceptible cells by NDV is influenced by the host cell in which the virus was propagated. The data also suggest that NDV may be useful in studies on homologous and heterologous membrane-membrane interactions. PMID:4858501

  3. Management of respiratory viral infections in hematopoietic cell transplant recipients

    PubMed Central

    Shah, Dimpy P; Ghantoji, Shashank S; Mulanovich, Victor E; Ariza-heredia, Ella J; Chemaly, Roy F

    2012-01-01

    Advances in stem cell transplantation procedures and the overall improvement in the clinical management of hematopoietic cell transplant (HCT) recipients over the past 2 decades have led to an increase in survival duration, in part owing to better strategies for prevention and treatment of post-transplant complications, including opportunistic infections. However, post-HCT infections remain a concern for HCT recipients, particularly infections caused by community respiratory viruses (CRVs), which can lead to significant morbidity and mortality. These viruses can potentially cause lower respiratory tract illness, which is associated with a higher mortality rate among HCT recipients. Clinical management of CRV infections in HCT recipients includes supportive care and antiviral therapy, especially in high-risk individuals, when available. Directed antiviral therapy is only available for influenza infections, where successful use of neuraminidase inhibitors (oseltamivir or zanamivir) and/or M2 inhibitors (amantadine or rimantadine) has been reported. Data on the successful use of ribavirin, with or without immunomodulators, for respiratory syncytial virus infections in HCT recipients has emerged over the past 2 decades but is still controversial at best because of a lack of randomized controlled trials. Because of the lack of directed antiviral therapy for most of these viruses, prevention should be emphasized for healthcare workers, patients, family, and friends and should include the promotion of the licensed inactivated influenza vaccine for HCT recipients, when indicated. In this review, we discuss the clinical management of respiratory viruses in this special patient population, focusing on commercially available antivirals, adjuvant therapy, and novel drugs under investigation, as well as on available means for prevention. PMID:23226621

  4. Mother-to-infant transmission of multiple blood-borne viral infections from multi-infected mothers.

    PubMed

    Indolfi, Giuseppe; Moriondo, Maria; Galli, Luisa; Azzari, Chiara; Poggi, Giovanni Maria; Resti, Massimo; de Martino, Maurizio

    2007-06-01

    Infants born from mothers with multiple blood-borne viral infections are at risk of multiple transmissions. Whether the risk of transmission of multiple infections increases with the number of viruses infecting the mother is still unknown. The aim of this study was to describe the risk of mother-to-infant transmission of multiple infections from multi-infected mothers. Sixty-four pregnant women infected by at least two viruses among human immunodeficiency virus-type 1 (HIV-1), hepatitis C virus, TT virus, and GB virus type C, together with their 64 infants, were studied. Maternal blood samples were collected in the third trimester of pregnancy and all infants were prospectively followed for evaluation of transmission within 3 months after birth and two times in the subsequent 24 months. Transmission of single and of dual infection from mothers infected by two viruses was, respectively, 10/40 (25%) and 5/40 (12.5%) and from mothers infected by three viruses 9/20 (45%) and 2/20 (10%). One (25%) infant infected by one virus was born from the four mothers infected by four viruses. Transmission of single or dual infection was not significantly associated with the number of viruses infecting the mother (P = 0.9) in the linear regression analysis. Present study suggests the absence of a synergistic effect from viral interactions toward mother-to-infant transmission of multiple infections and supports the hypothesis that transmission from multi-infected mothers is the result of the specific interaction between each virus and the host. These observations may be of clinical relevance in perinatal counseling. (c) 2007 Wiley-Liss, Inc.

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

    USDA-ARS?s Scientific Manuscript database

    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...

  6. Value of serological tests in the diagnosis of viral acute respiratory infections in adults.

    PubMed

    Căruntu, F; Dogaru, D; Stefan, D; Căruntu, V; Angelescu, C; Streinu-Cercel, A; Colţan, G; Petrescu, A L; Tarţă, D; Bârnaure, F

    1986-01-01

    The dynamics of the antibody response to influenza viruses A (H1N1), A (H3N2) and B, to parainfluenza viruses 1, 2, 3, to adenoviruses and respiratory syncytial virus was studied in paired serum samples collected from 110 patients hospitalized with acute respiratory infections (ARI) and in 40 patients suffering from other diseases. Rises in serum antibody titers to 1--5 of the above mentioned antigens were detected in many of the patients of both groups. The fact is most likely due to the presence of some epidemiologically and clinically uncharacteristic viral ARI (influenza included); simultaneous or successive infections with influenza virus and different other viruses were very frequent. A greater efficiency of the etiological diagnosis of viral ARI can be achieved only by the association of epidemiological and clinical criteria with serological data, the visualization of viral antigens and virus isolation.

  7. Nuclear Sensing of Viral DNA, Epigenetic Regulation of Herpes Simplex Virus Infection, and Innate Immunity

    PubMed Central

    Knipe, David M.

    2015-01-01

    Herpes simplex virus (HSV) undergoes a lytic infection in epithelial cells and a latent infection in neuronal cells, and epigenetic mechanisms play a major role in the differential gene expression under the two conditions. Herpes viron DNA is not associated with histones but is rapidly loaded with heterochromatin upon entry into the cell. Viral proteins promote reversal of the epigenetic silencing in epithelial cells while the viral latency-associated transcript promotes additional heterochromatin in neuronal cells. The cellular sensors that initiate the chromatinization of foreign DNA have not been fully defined. IFI16 and cGAS are both essential for innate sensing of HSV DNA, and new evidence shows how they work together to initiate innate signaling. IFI16 also plays a role in the heterochromatinization of HSV DNA, and this review will examine how IFI16 integrates epigenetic regulation and innate sensing of foreign viral DNA to show how these two responses are related. PMID:25742715

  8. Transkingdom control of viral infection and immunity in the mammalian intestine

    PubMed Central

    Pfeiffer, Julie K.; Virgin, Herbert W.

    2016-01-01

    Viruses that infect the intestine include major human pathogens (retroviruses, noroviruses, rotaviruses, astroviruses, picornaviruses, adenoviruses, herpesviruses) constituting a major public health problem worldwide. These viral pathogens are members of a large, complex viral community inhabiting the intestine termed the enteric virome. Enteric viruses have intimate functional and genetic relationships with both the host and other microbial constituents that inhabit the intestine, like the bacterial microbiota, their associated phages, helminthes and fungi which together constitute the microbiome. Emerging data indicate that enteric viruses regulate, and are in turn regulated by, these other microbes through a series of processes termed transkingdom interactions. This represents a changing paradigm in intestinal immunity to viral infection. Here we review recent advances in the field and propose new ways in which to conceptualize this important area. PMID:26816384

  9. Nutrition, immunity and viral infections in honey bees

    USDA-ARS?s Scientific Manuscript database

    Honey bees can be infected with viruses that can spread rapidly in colonies. Here we discuss how honey bees decrease the risk of disease outbreaks by a combination of behaviors (social immunity) and individual immunity. The effectiveness of both social and individual immunity relies on nutrition. Ho...

  10. Viral infection of human lung macrophages increases PDL1 expression via IFNβ.

    PubMed

    Staples, Karl J; Nicholas, Ben; McKendry, Richard T; Spalluto, C Mirella; Wallington, Joshua C; Bragg, Craig W; Robinson, Emily C; Martin, Kirstin; Djukanović, Ratko; Wilkinson, Tom M A

    2015-01-01

    Lung macrophages are an important defence against respiratory viral infection and recent work has demonstrated that influenza-induced macrophage PDL1 expression in the murine lung leads to rapid modulation of CD8+ T cell responses via the PD1 receptor. This PD1/PDL1 pathway may downregulate acute inflammatory responses to prevent tissue damage. The aim of this study was to investigate the mechanisms of PDL1 regulation by human macrophages in response to viral infection. Ex-vivo viral infection models using influenza and RSV were established in human lung explants, isolated lung macrophages and monocyte-derived macrophages (MDM) and analysed by flow cytometry and RT-PCR. Incubation of lung explants, lung macrophages and MDM with X31 resulted in mean cellular infection rates of 18%, 18% and 29% respectively. Viral infection significantly increased cell surface expression of PDL1 on explant macrophages, lung macrophages and MDM but not explant epithelial cells. Infected MDM induced IFNγ release from autologous CD8+ T cells, an effect enhanced by PDL1 blockade. We observed increases in PDL1 mRNA and IFNβ mRNA and protein release by MDM in response to influenza infection. Knockdown of IFNβ by siRNA, resulted in a 37.5% reduction in IFNβ gene expression in response to infection, and a significant decrease in PDL1 mRNA. Furthermore, when MDM were incubated with IFNβ, this cytokine caused increased expression of PDL1 mRNA. These data indicate that human macrophage PDL1 expression modulates CD8+ cell IFNγ release in response to virus and that this expression is regulated by autologous IFNβ production.

  11. Communication via extracellular vesicles enhances viral infection of a cosmopolitan alga.

    PubMed

    Schatz, Daniella; Rosenwasser, Shilo; Malitsky, Sergey; Wolf, Sharon G; Feldmesser, Ester; Vardi, Assaf

    2017-09-18

    Communication between microorganisms in the marine environment has immense ecological impact by mediating trophic-level interactions and thus determining community structure (1) . Extracellular vesicles (EVs) are produced by bacteria (2,3) , archaea (4) , protists (5) and metazoans, and can mediate pathogenicity (6) or act as vectors for intercellular communication. However, little is known about the involvement of EVs in microbial interactions in the marine environment (7) . Here we investigated the signalling role of EVs produced during interactions between the cosmopolitan alga Emiliania huxleyi and its specific virus (EhV, Phycodnaviridae) (8) , which leads to the demise of these large-scale oceanic blooms (9,10) . We found that EVs are highly produced during viral infection or when bystander cells are exposed to infochemicals derived from infected cells. These vesicles have a unique lipid composition that differs from that of viruses and their infected host cells, and their cargo is composed of specific small RNAs that are predicted to target sphingolipid metabolism and cell-cycle pathways. EVs can be internalized by E. huxleyi cells, which consequently leads to a faster viral infection dynamic. EVs can also prolong EhV half-life in the extracellular milieu. We propose that EVs are exploited by viruses to sustain efficient infectivity and propagation across E. huxleyi blooms. As these algal blooms have an immense impact on the cycling of carbon and other nutrients (11,12) , this mode of cell-cell communication may influence the fate of the blooms and, consequently, the composition and flow of nutrients in marine microbial food webs.Infection of the alga Emiliania huxleyi with its virus EhV results in the increased release of extracellular vesicles that impact viral decay and infection, suggesting that EhV exploits these extracellular vesicles for efficient viral infection during algal blooms.

  12. Canine viral enteritis: prevalence of parvo-, corona- and rotavirus infections in dogs in the Netherlands.

    PubMed

    Osterhaus, A D; Drost, G A; Wirahadiredja, R M; van den Ingh, T S

    1980-10-15

    After a brief review of the present knowledge about canine viral enteritis, the role played by parvoviral, coronaviral and rotaviral infections in contagious diarrhoea in dogs in the Netherlands is discussed. For this purpose a serologic survey, pathologic findings in dogs, and the demonstration of parvoviral antigen with an immunofluorescence test and with a newly developed haemadsorption-elution-haemagglutination assay (HEHA) are presented. It is concluded that infections with canine parvovirus, coronavirus and rotavirus appear widespread among dog populations in the Netherlands.

  13. Does Viral Co-Infection Influence the Severity of Acute Respiratory Infection in Children?

    PubMed Central

    Pardo-Seco, Jacobo; Gómez-Carballa, Alberto; Martinón-Torres, Nazareth; Salas, Antonio; Martinón-Sánchez, José María; Justicia, Antonio; Rivero-Calle, Irene; Sumner, Edward; Fink, Colin

    2016-01-01

    Background Multiple viruses are often detected in children with respiratory infection but the significance of co-infection in pathogenesis, severity and outcome is unclear. Objectives To correlate the presence of viral co-infection with clinical phenotype in children admitted with acute respiratory infections (ARI). Methods We collected detailed clinical information on severity for children admitted with ARI as part of a Spanish prospective multicenter study (GENDRES network) between 2011–2013. A nested polymerase chain reaction (PCR) approach was used to detect respiratory viruses in respiratory secretions. Findings were compared to an independent cohort collected in the UK. Results 204 children were recruited in the main cohort and 97 in the replication cohort. The number of detected viruses did not correlate with any markers of severity. However, bacterial superinfection was associated with increased severity (OR: 4.356; P-value = 0.005), PICU admission (OR: 3.342; P-value = 0.006), higher clinical score (1.988; P-value = 0.002) respiratory support requirement (OR: 7.484; P-value < 0.001) and longer hospital length of stay (OR: 1.468; P-value < 0.001). In addition, pneumococcal vaccination was found to be a protective factor in terms of degree of respiratory distress (OR: 2.917; P-value = 0.035), PICU admission (OR: 0.301; P-value = 0.011), lower clinical score (-1.499; P-value = 0.021) respiratory support requirement (OR: 0.324; P-value = 0.016) and oxygen necessity (OR: 0.328; P-value = 0.001). All these findings were replicated in the UK cohort. Conclusion The presence of more than one virus in hospitalized children with ARI is very frequent but it does not seem to have a major clinical impact in terms of severity. However bacterial superinfection increases the severity of the disease course. On the contrary, pneumococcal vaccination plays a protective role. PMID:27096199

  14. ModeLang: A New Approach for Experts-Friendly Viral Infections Modeling

    PubMed Central

    Blazewicz, Jacek

    2013-01-01

    Computational modeling is an important element of systems biology. One of its important applications is modeling complex, dynamical, and biological systems, including viral infections. This type of modeling usually requires close cooperation between biologists and mathematicians. However, such cooperation often faces communication problems because biologists do not have sufficient knowledge to understand mathematical description of the models, and mathematicians do not have sufficient knowledge to define and verify these models. In many areas of systems biology, this problem has already been solved; however, in some of these areas there are still certain problematic aspects. The goal of the presented research was to facilitate this cooperation by designing seminatural formal language for describing viral infection models that will be easy to understand for biologists and easy to use by mathematicians and computer scientists. The ModeLang language was designed in cooperation with biologists and its computer implementation was prepared. Tests proved that it can be successfully used to describe commonly used viral infection models and then to simulate and verify them. As a result, it can make cooperation between biologists and mathematicians modeling viral infections much easier, speeding up computational verification of formulated hypotheses. PMID:24454531

  15. Viral infection and innate pattern recognition receptors in induction of Hashimoto's thyroiditis.

    PubMed

    Morohoshi, Kazuki; Takahashi, Yurie; Mori, Kouki

    2011-12-01

    Hashimoto's thyroiditis, a common organ-specific autoimmune disease, is multifactorial in which both genetic susceptibility and environmental factors including infection play a critical role in its pathogenesis. Viral infection activates both the innate and adaptive immunity and is implicated as a trigger of Hashimoto's thyroiditis. Candidate viruses include hepatitis C virus and human parvovirus B19. Viral components, which are recognized by innate receptors including Toll-like receptors (TLRs), are detected in thyroid tissues and sera of patients with Hashimoto's thyroiditis. While conflicting results have been obtained regarding the role of TLRs in autoimmune diseases, our preliminary study suggested a contribution of TLR2 and dectin-1 in combination, TLR4, or TLR7 to the production of anti-thyroglobulin antibody in nonobese diabetic mice, a mouse model of Hashimoto's thyroiditis. Despite interesting circumstantial evidence, however, whether viral infection and innate receptors are involved in the development of Hashimoto's thyroiditis remains largely unclear. In this review, we summarize our knowledge regarding the role of viral infection and innate receptors in the etiology of Hashimoto's thyroiditis.

  16. Effects of Viral Infection on Blood-Feeding Behavior in Culicoides sonorensis (Diptera: Ceratopogonidae)

    USDA-ARS?s Scientific Manuscript database

    Culicoides sonorensis (Diptera: Ceratopogonidae) is the primary vector of bluetongue virus (BTV) in North America and a competent vector of vesicular stomatitis virus (VSV). Little is known about how viral infection of this midge affects its blood feeding behavior. Midges were intrathoracically inoc...

  17. Effects of Viral Infection on Blood Feeding Behavior and Fecundity in Culicoides Sonorensis (Diptera: Ceratopogonidae)

    USDA-ARS?s Scientific Manuscript database

    Culicoides sonorensis (Diptera: Ceratopogonidae) is the primary vector of bluetongue virus (BTV) in North America and a competent vector of vesicular stomatitis virus (VSV). Little is known about how viral infection of this midge affects its blood feeding behavior and fecundity. Blood feeding succes...

  18. Improved impression cytology techniques for the immunopathological diagnosis of superficial viral infections

    PubMed Central

    Thiel, M; Bossart, W; Bernauer, W

    1997-01-01

    BACKGROUND—For epidemiological and therapeutic reasons early diagnosis of superficial viral infections is crucial. Conventional microbiological techniques are expensive, time consuming, and not sufficiently sensitive. In this study impression cytology techniques were evaluated to analyse their diagnostic potential in viral infections of the ocular surface.
METHOD—A Biopore membrane device instead of the original impression cytology technique was used to allow better quality and handling of the specimens. The impressions were processed, using monoclonal antibodies and immunoperoxidase or immunofluorescence techniques to assess the presence of herpes simplex virus, varicella zoster virus, or adenovirus antigens. Ocular surface specimens from healthy individuals (n=10) and from patients with suspected viral surface disease (n=19) were studied. Infected and non-infected cell cultures served as controls.
RESULTS—This modified technique of impression cytology allowed the collection of large conjunctival and corneal epithelial cell layers with excellent morphology. Immunocytological staining of these samples provided diagnostic results for all three viruses in patients with viral surface disease.
CONCLUSIONS—The use of Biopore membrane devices for the collection of ocular surface epithelia offers new diagnostic possibilities for external eye diseases. Immunopathological methods that are applied directly on these membrane devices can provide virological results within 1-4 hours. This contributes considerably to the clinical management of patients with infectious diseases of the ocular surface.

 PMID:9505824

  19. Resolving bovine viral diarrhea virus subtypes from persistently infected US beef calves with complete genome sequence

    USDA-ARS?s Scientific Manuscript database

    Bovine viral diarrhea virus (BVDV) is classified into 2 genotypes, BVDV-1 and BVDV-2, each of which contains distinct subtypes with genetic and antigenic differences. Currently, three major subtypes circulate in the United States: BVDV-1a, 1b, and 2a. In addition, a single case of BVDV-2b infection ...

  20. At the crossroads of autophagy and infection: Noncanonical roles for ATG proteins in viral replication

    PubMed Central

    Solvik, Tina

    2016-01-01

    Autophagy-related (ATG) proteins have increasingly demonstrated functions other than cellular self-eating. In this issue, Mauthe et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201602046) conduct an unbiased RNA interference screen of the ATG proteome to reveal numerous noncanonical roles for ATG proteins during viral infection. PMID:27573461

  1. Noninvasive visualization of respiratory viral infection using bioorthogonal conjugated near-infrared-emitting quantum dots.

    PubMed

    Pan, Hong; Zhang, Pengfei; Gao, Duyang; Zhang, Yijuan; Li, Ping; Liu, Lanlan; Wang, Ce; Wang, Hanzhong; Ma, Yifan; Cai, Lintao

    2014-06-24

    Highly pathogenic avian influenza A viruses are emerging pandemic threats in human beings. Monitoring the in vivo dynamics of avian influenza viruses is extremely important for understanding viral pathogenesis and developing antiviral drugs. Although a number of technologies have been applied for tracking viral infection in vivo, most of them are laborious with unsatisfactory detection sensitivity. Herein we labeled avian influenza H5N1 pseudotype virus (H5N1p) with near-infrared (NIR)-emitting QDs by bioorthogonal chemistry. The conjugation of QDs onto H5N1p was highly efficient with superior stability both in vitro and in vivo. Furthermore, QD-labeled H5N1p (QD-H5N1p) demonstrated bright and sustained fluorescent signals in mouse lung tissues, allowing us to visualize respiratory viral infection in a noninvasive and real-time manner. The fluorescence signals of QD-H5N1p in lung were correlated with the severity of virus infection and significantly attenuated by antiviral agents, such as oseltamivir carboxylate and mouse antiserum against H5N1p. The biodistribution of QD-H5N1p in lungs and other organs could be easily quantified by measuring fluorescent signals and cadmium concentration of virus-conjugated QDs in tissues. Hence, virus labeling with NIR QDs provides a simple, reliable, and quantitative strategy for tracking respiratory viral infection and for antiviral drug screening.

  2. Comment on ‘Dengue viral infection monitoring from diagnostic to recovery using Raman spectroscopy’

    NASA Astrophysics Data System (ADS)

    Darvin, Maxim E.; Lademann, Juergen; Brandt, Nikolay N.

    2016-04-01

    The results of the letter ‘Dengue viral infection monitoring from diagnostic to recovery using Raman spectroscopy’ authored by Firdous and Anwar (2015 Laser Phys. Lett. 12 085601) are discussed. We show that the original interpretation of the results is not correct and does not correspond to data in the literature.

  3. Case Report: Emergence of bovine viral diarrhea virus persistently infected calves in a closed herd

    USDA-ARS?s Scientific Manuscript database

    Bovine viral diarrhea virus (BVDV) continues to have significant economic impact on the cattle industry worldwide. The virus is primarily maintained in the cattle population due to persistently infected animals. Herd surveillance along with good vaccination programs and biosecurity practices are the...

  4. Low viral doses are sufficient to infect cottontail rabbits with avian influenza A virus.

    PubMed

    Root, J Jeffrey; Shriner, Susan A; Ellis, Jeremy W; VanDalen, Kaci K; Sullivan, Heather J

    2017-08-02

    Influenza A viruses (IAVs) have been reported in wild lagomorphs in environments where they share resources with waterfowl. Recent studies have conclusively shown that a North American lagomorph, cottontail rabbits (Sylvilagus sp.), become infected following exposure to IAVs and can shed significant quantities of virus. However, the minimum infectious dose and the efficiency of various routes of infection have not been evaluated. Thirty-six cottontail rabbits were used in a dose response study assessing both the oral and nasal routes of infection. The nasal route of infection proved to be the most efficient, as all cottontail rabbits shed viral RNA following inoculation with doses as low as 10(2) EID50. The oral route of infection was less efficient, but still produced infection rates of ≥ 50% at relatively low doses (i.e., 10(3) and 10(4) EID50). These results suggest that cottontail rabbits are highly susceptible to IAVs at low exposure doses that have been routinely observed in environments contaminated by waterfowl. Furthermore, this study supports earlier observations that cottontail rabbits may pose a biosecurity risk to poultry operations, as a virus-contaminated water source or contaminated environment, even at low viral titers, could be sufficient to initiate viral replication in cottontail rabbits.

  5. Clinical and Associated Immunological Manifestations of HFMD Caused by Different Viral Infections in Children

    PubMed Central

    Wang, Jingjing; Pu, Jing; Liu, Longding; Che, Yanchun; Liao, Yun; Wang, Lichun; Guo, Lei; Feng, Min; Liang, Yan; Fan, Shengtao; Cai, Lukui; Zhang, Ying; Li, Qihan

    2016-01-01

    Hand, foot, and mouth disease (HFMD), with vesiculae on the hands, feet and mouth, is an infectious disease caused by many viral pathogens. However, the differences of immune response induced by these pathogens are unclear. We compared the clinical manifestations and the levels of immunologic indicators from 60 HFMD patients caused by different viral pathogens to analyze the differences in the immune response. It was shown that Th2 cytokines (IL-4 and IL-10) increased significantly in EV71-infected children; Th1 cytokines (IL-2 and IFN-γ) rose in CA16-infected children; both Th1 and Th2 cytokines elevated in non-EVG-infected children; only individual cytokines (such as IL-10) went up in EVG-infected children. Meanwhile, the antibodies induced by viral infection could not cross-interfere between the different pathogens. These differences might be due to variations in the immune response induced by the individual pathogens or to the pathogenesis of the infections by the individual pathogens. PMID:27336013

  6. A DNA aptamer efficiently inhibits the infectivity of Bovine herpesvirus 1 by blocking viral entry.

    PubMed

    Xu, Jian; Zhang, Xixi; Zhou, Shuanghai; Shen, Junjun; Yang, Dawei; Wu, Jing; Li, Xiaoyang; Li, Meiling; Huang, Xiufen; Sealy, Joshua E; Iqbal, Munir; Li, Yongqing

    2017-09-18

    Bovine herpesvirus 1 (BoHV-1) is an important pathogen of domestic and wild cattle responsible for major economic losses in dairy and beef industries throughout the world. Inhibition of viral entry plays a crucial role in the control of BoHV-1 infection and aptamers have been reported to inhibit viral replication. In this study, nine DNA aptamers that target BoHV-1 were generated using systemic evolution of ligands by exponential enrichment. Of the nine candidates, aptamer IBRV-A4 exhibited the highest affinity and specificity for BoHV-1, which bound to BoHV-1 with a Kd value of 3.519 nM and demonstrated the greatest virus binding as shown by fluorescence imaging. The neutralizing ability of aptamer IBRV-A4 was determined using neutralization assays and real time PCR in BoHV-1 infected Madin-darby bovine kidney cells. Virus titration, immunofluorescence and confocal laser scanning microscopy showed virus replication significantly decreased when aptamer IBRV-A4 was added to BoHV-1 infected MDBK cells at 0 and 0.5 hours post-infection, whereas no change was seen when IBRV-A4 was added 2 hours post-infection. This concludes that aptamer IBRV-A4 efficiently inhibits viral entry of BoHV-1 in MDBK cells and is therefore a novel tool for diagnosis and treatment of BoHV-1 infection in cattle.

  7. NK cell-mediated immunopathology during an acute viral infection of the CNS.

    PubMed

    Alsharifi, Mohammed; Lobigs, Mario; Simon, Markus M; Kersten, Astrid; Müller, Klaus; Koskinen, Aulikki; Lee, Eva; Müllbacher, Arno

    2006-04-01

    Natural killer (NK) and cytotoxic T (Tc) cells are prime effector populations in the antiviral response of the host. Tc cells are essential for recovery from many viral diseases but may also be responsible for immunopathology. The role of NK cells in recovery from viral infections is less well established. We have studied acute virulent Semliki Forest virus (vSFV) infection of the central nervous system in C57BL/6J mice, which was mainly controlled by NK cells without marked Tc cell involvement. We show that mice with defects in the Fas and/or granule exocytosis pathways of cytotoxicity are more resistant to lethal vSFV infection than wild-type mice. On the other hand, mice defective in the IFN-gamma response are more sensitive than wild-type mice, whereas mice lacking the Tc cell compartment (beta-2 microglobulin-deficient mice) exhibit susceptibility similar to wild-type mice. The additional finding that depletion of NK cells significantly delayed the mean time to death but did not prevent mortality in SFV-infected B6 mice suggests that cytolytic activity of NK cells is detrimental, while IFN-gamma production is beneficial for recovery from SFV infection. This is the first study illustrating an NK cell-mediated immunopathological outcome to an acute viral infection.

  8. Chronic and persistent viral hemorrhagic septicemia virus infections in Pacific herring

    USGS Publications Warehouse

    Hershberger, P.K.; Gregg, J.L.; Grady, C.A.; Taylor, L.; Winton, J.R.

    2010-01-01

    Chronic viral hemorrhagic septicemia virus (VHSV) infections were established in a laboratory stock of Pacific herring Clupea pallasii held in a large-volume tank supplied with pathogenfree seawater at temperatures ranging from 6.8 to 11.6??C. The infections were characterized by viral persistence for extended periods and near-background levels of host mortality. Infectious virus was recovered from mortalities occurring up to 167 d post-exposure and was detected in normal-appearing herring for as long as 224 d following initial challenge. Geometric mean viral titers were generally as high as or higher in brain tissues than in pools of kidney and spleen tissues, with overall prevalence of infection being higher in the brain. Upon re-exposure to VHSV in a standard laboratory challenge, negligible mortality occurred among groups of herring that were either chronically infected or fully recovered, indicating that survival from chronic manifestations conferred protection against future disease. However, some survivors of chronic VHS infections were capable of replicating virus upon re-exposure. Demonstration of a chronic manifestation of VHSV infection among Pacific herring maintained at ambient seawater temperatures provides insights into the mechanisms by which the virus is maintained among populations of endemic hosts. ?? 2010 Inter-Research.

  9. Chronic and persistent viral hemorrhagic septicemia virus infections in Pacific herring

    USGS Publications Warehouse

    Hershberger, Paul K.; Gregg, Jacob L.; Winton, James R.; Grady, Cortney A.; Taylor, L.

    2010-01-01

    Chronic viral hemorrhagic septicemia virus (VHSV) infections were established in a laboratory stock of Pacific herring Clupea pallasii held in a large-volume tank supplied with pathogen-free seawater at temperatures ranging from 6.8 to 11.6°C. The infections were characterized by viral persistence for extended periods and near-background levels of host mortality. Infectious virus was recovered from mortalities occurring up to 167 d post-exposure and was detected in normal-appearing herring for as long as 224 d following initial challenge. Geometric mean viral titers were generally as high as or higher in brain tissues than in pools of kidney and spleen tissues, with overall prevalence of infection being higher in the brain. Upon re-exposure to VHSV in a standard laboratory challenge, negligible mortality occurred among groups of herring that were either chronically infected or fully recovered, indicating that survival from chronic manifestations conferred protection against future disease. However, some survivors of chronic VHS infections were capable of replicating virus upon re-exposure. Demonstration of a chronic manifestation of VHSV infection among Pacific herring maintained at ambient seawater temperatures provides insights into the mechanisms by which the virus is maintained among populations of endemic hosts.

  10. Emerging Infections: Lessons from the Viral Hemorrhagic Fevers

    PubMed Central

    Peters, C. J

    2006-01-01

    Two Institute of Medicine reports since 1992 have emphasized the dangerous and continuing threat to the world from emerging infectious diseases. Working with viral hemorrhagic fevers provides a number of lessons related to the processes that control emergence, the pattern of disease after emergence, and how to cope with these incidents. This short paper uses two arenavirus hemorrhagic fevers to illustrate some of these principles. Argentine and Bolivian hemorrhagic fevers first came to medical attention in the 1950’s. The forces that underlie the emergence of disease in Argentina are not understood, but the Bolivian episode has a reasonably understandable train of events behind it. The Argentine disease had serious impact on the large agricultural economy, and the ecology of the rodent reservoir did not lend itself to control; a vaccine was developed by Argentina and the U.S. with the latter motivated largely by biodefense. The Bolivian disease was controlled in large part by eliminating rodents that invaded towns, and the impact was subsequently below the level needed to trigger drug or vaccine development. These two viruses were important in the recognition of a new family of viruses (Arenaviridae), and this finding of new taxons during the investigation of emerging infectious diseases continues. PMID:18528473

  11. Toscana meningoencephalitis: a comparison to other viral central nervous system infections

    PubMed Central

    Jaijakul, Siraya; Arias, Cesar A.; Hossein, Monir; Arduino, Roberto C.; Wootton, Susan H.; Hasbun, Rodrigo

    2012-01-01

    Background Toscana virus (TOSV) is an emerging pathogen causing central nervous system (CNS) infection in Mediterranean countries, mostly during summer season. Objectives To compare the clinical and laboratory characteristics of Toscana CNS infections to the most common viral pathogens seen in the United States. Study Design We performed a case series of patients with 41 TOSV infection and compared the clinical characteristics, laboratory findings, imaging results and clinical outcomes to the most commonly recognized viral causes of meningoencephalitis in the US (enterovirus (n=60), herpes simplex virus (n=48), and west nile virus (n=30) from our multi-center study of patients with aseptic meningoencephalitis syndromes in the Greater Houston area. Results TOSV infection occurs in different age groups compared to enterovirus, HSV, and WNV. All infections most frequently occur during summer-fall except HSV which distributes throughout the year. All patients with TOSV had history of travel to endemic areas. There are differences in clinical presentation and CSF findings comparing TOSV and enterovirus, HSV, and WNV infection. There are no significant differences in outcomes of each infection except WNV meningoencephalitis which had a poorer outcome compared to TOSV infection. Conclusions TOSV is an emerging pathogen that should be considered in the differential diagnosis of patients with CNS infections and a recent travel history to endemic areas. PMID:22867730

  12. Zika Virus Infection of the Human Glomerular Cells: Implications for Viral Reservoirs and Renal Pathogenesis.

    PubMed

    Alcendor, Donald J

    2017-07-15

    Zika virus (ZIKV) infection in the human renal compartment has not been reported. Several clinical reports have describe high-level persistent viral shedding in the urine of infected patients, but the associated mechanisms have not been explored until now. The current study examined cellular components of the glomerulus of the human kidney for ZIKV infectivity. I infected primary human podocytes, renal glomerular endothelial cells (GECs), and mesangial cells with ZIKV. Viral infectivity was analyzed by means of microscopy, immunofluorescence, real-time reverse-transcription polymerase chain reaction (RT-PCR), and quantitative RT-PCR (qRT-PCR), and the proinflammatory cytokines interleukin 1β, interferon β, and RANTES (regulated on activation of normal T cells expressed and secreted) were assessed using qRT-PCR. I show that glomerular podocytes, renal GECs, and mesangial cells are permissive for ZIKV infection. ZIKV infectivity was confirmed in all 3 cell types by means of immunofluorescence staining, RT-PCR, and qRT-PCR, and qRT-PCR analysis revealed increased transcriptional induction of interleukin 1β, interferon β, and RANTES in ZIKV-infected podocytes at 72 hours, compared with renal GECs and mesangial cells. The findings of this study support the notion that the glomerulus may serve as an amplification reservoir for ZIKV in the renal compartment. The impact of ZIKV infection in the human renal compartment is unknown and will require further study.

  13. Modelling and analysis of dynamics of viral infection of cells and of interferon resistance

    NASA Astrophysics Data System (ADS)

    Getto, Ph.; Kimmel, M.; Marciniak-Czochra, A.

    2008-08-01

    Interferons are active biomolecules, which help fight viral infections by spreading from infected to uninfected cells and activate effector molecules, which confer resistance from the virus on cells. We propose a new model of dynamics of viral infection, including endocytosis, cell death, production of interferon and development of resistance. The novel element is a specific biologically justified mechanism of interferon action, which results in dynamics different from other infection models. The model reflects conditions prevailing in liquid cultures (ideal mixing), and the absence of cells or virus influx from outside. The basic model is a nonlinear system of five ordinary differential equations. For this variant, it is possible to characterise global behaviour, using a conservation law. Analytic results are supplemented by computational studies. The second variant of the model includes age-of-infection structure of infected cells, which is described by a transport-type partial differential equation for infected cells. The conclusions are: (i) If virus mortality is included, the virus becomes eventually extinct and subpopulations of uninfected and resistant cells are established. (ii) If virus mortality is not included, the dynamics may lead to extinction of uninfected cells. (iii) Switching off the interferon defense results in a decrease of the sum total of uninfected and resistant cells. (iv) Infection-age structure of infected cells may result in stabilisation or destabilisation of the system, depending on detailed assumptions. Our work seems to constitute the first comprehensive mathematical analysis of the cell-virus-interferon system based on biologically plausible hypotheses.

  14. Involvement of Interleukin 6 in Hepatitis B Viral Infection.

    PubMed

    Xia, Caixia; Liu, Yanning; Chen, Zhi; Zheng, Min

    2015-01-01

    Hepatitis B is a major global health problem and a potentially life-threatening liver infection caused by hepatitis B virus (HBV). Many cytokines including interleukin 6 (IL-6) have been shown to be involved in the HBV infection process. IL-6 is a typical cytokine made up of 184 amino acids, and the gene is located in chromosome 7p21. For healthy people, serum IL-6 levels are usually too low to be detected. However, dysregulated synthesis of IL-6 has been discovered in chronic inflammatory diseases such as hepatitis B, Crohn's disease and rheumatoid arthritis. IL-6 also plays an important role in HBV replication and in the development of hepatitis B disease. This review aims to present the latest discoveries concerning the role of IL-6 in hepatitis B disease progression, and HBV entry and replication, and evaluate polymorphisms that are associated with the development of hepatitis B disease.

  15. Fibrillary glomerulonephritis with hepatitis C viral infection and hypocomplementemia.

    PubMed

    Ray, Susan; Rouse, Kelly; Appis, Andrew; Novak, Robert; Haller, Nairmeen Awad

    2008-01-01

    Fibrillary glomerulonephritis (FGN) is a relatively rare cause of renal disease, found in only 0.6-1.5% of native renal biopsies. The pathogenesis of FGN is not well described, and very few associations with disease processes other than hepatitis C virus (HCV) have been made. We describe a case that provides evidence in support of the FGN-HCV association, as well as introduces the association of FGN-HCV and hypocomplementemia. The case is a 53-year-old African-American female demonstrating a classical presentation of FGN complicated by a concomitant HCV infection. Treating an HCV infection with alpha-interferon has been shown to result in subsequent improvement in the nephrotic syndrome and renal function. However, this patient is unique in that she is complicated with hypocomplementemia, creating a complex treatment situation.

  16. Causes of thrombocytopenia in chronic hepatitis C viral infection.

    PubMed

    Osada, Makoto; Kaneko, Makoto; Sakamoto, Minoru; Endoh, Masumi; Takigawa, Koichi; Suzuki-Inoue, Katsue; Inoue, Osamu; Satoh, Kaneo; Enomoto, Nobuyuki; Yatomi, Yutaka; Ozaki, Yukio

    2012-06-01

    We retrospectively studied 89 patients with chronic hepatitis C virus (HCV) infection, including 50 chronic hepatitis (CH) cases, 18 liver cirrhosis (LC) cases, and 21 LC with hepatocellular carcinoma (LC + HCC) cases, with regard to various factors related with thrombocytopenia. The platelet count decreased with the stage advancement of liver diseases. Multiple regression analysis revealed that splenomegaly and von Willebrand factor (vWF) were explanatory variables that correlated with thrombocytopenia. Splenomegaly appears to be the most responsible factor, although there are a considerable number of thrombocytopenic cases without splenomegaly, suggesting other factors may also be responsible. The vWF level is inversely correlated with the platelet count. Soluble thrombomodulin, a marker of endothelial dysfunction, increases with the advancement of liver fibrosis. It is positively correlated with vWF and inversely with the platelet count. Our present results imply that vascular endothelial dysfunction is also involved in thrombocytopenia during chronic HCV infection.

  17. Heat Shock Protein 27 Mediated Signaling in Viral Infection

    PubMed Central

    Rajaiya, Jaya; Yousuf, Mohammad A.; Singh, Gurdeep; Stanish, Heather; Chodosh, James

    2013-01-01

    Heat shock proteins (HSPs) play a critical role in many intracellular processes, including apoptosis and delivery of other proteins to intracellular compartments. Small HSPs have been shown previously to participate in many cellular functions, including IL-8 induction. Human adenovirus infection activates intracellular signaling, involving particularly the c-Src and mitogen-activated protein kinases [Natarajan, K., et al. (2003) J. Immunol. 170, 6234–6243]. HSP27 and MK2 are also phosphorylated, and c-Src, and its downstream targets, p38, ERK1/2, and c-Jun-terminal kinase (JNK), differentially mediate IL-8 and MCP-1 expression. Specifically, activation and translocation of transcription factor NFκB-p65 occurs in a p38-dependent fashion [Rajaiya, J., et al. (2009) Mol. Vision 15, 2879–2889]. Herein, we report a novel role for HSP27 in an association of p38 with NFκB-p65. Immunoprecipitation assays of virus-infected but not mock-infected cells revealed a signaling complex including p38 and NFκB-p65. Transfection with HSP27 short interfering RNA (siRNA) but not scrambled RNA disrupted this association and reduced the level of IL-8 expression. Transfection with HSP27 siRNA also reduced the level of nuclear localization of NFκB-p65 and p38. By use of tagged p38 mutants, we found that amino acids 279–347 of p38 are necessary for the association of p38 with NFκB-p65. These studies strongly suggest that HSP27, p38, and NFκB-p65 form a signalosome in virus-infected cells and influence downstream expression of pro-inflammatory mediators. PMID:22734719

  18. Similar pattern of chemokines after acute viral and bacterial infection.

    PubMed

    Vyas, Ashish Kumar

    2017-01-27

    Read with great interest the article by Cavalcanti et al (1). Which describes the levels of chemokine such as MCP-1, RANETS, MIG and IP-10 in children with sepsis community acquired pneumonia and skin abscess. Author has found increased levels of RANETS in all infections mentioned above. Interestingly IP-10 was significantly increased in sepsis groups with low levels of MCP1. This article is protected by copyright. All rights reserved.

  19. MECHANISMS OF RECOVERY FROM A GENERALIZED VIRAL INFECTION: MOUSEPOX

    PubMed Central

    Blanden, R. V.

    1971-01-01

    Histological and immunofluorescence techniques showed that mononuclear cells invaded virus-infected foci in the livers of passively immunized mice within 10 hr of the receipt of immune spleen cells or hyperimmune serum; by 24 hr, marked destruction of virus antigens had occurred in these lesions. Immune cell transfer promoted denser packing of mononuclear cells in the foci and more efficient destruction of infectious material than immune serum. Similar liver lesions developed by the 6th day after sublethal, primary, subcutaneous infection in normal mice. In contrast, in mice with GVHR which were immunosuppressed but possessed hyperactive macrophages and unimpaired splenic interferon response, mononuclear cells did not invade liver lesions and the animals died. These results, together with data reported previously, indicated that mononuclear cell invasion of infected liver foci, triggered by CMI, was of key importance in recovery from primary mousepox. The roles of specifically sensitized lymphocytes and macrophages within lesions were not directly evaluated, but indirect evidence suggested that lymphocytes could cause no more than a halt in virus multiplication, and that macrophages were required for the inactivation of preformed virions. Possible augmentation of the efficiency of macrophages by locally-produced lymphocyte interferon, neutralizing antibody, or stimulation of their phagocytic and intracellular digestive capacity cannot be excluded. PMID:4324301

  20. Prophylactic managements of hepatitis B viral infection in liver transplantation

    PubMed Central

    Onoe, Takashi; Tahara, Hiroyuki; Tanaka, Yuka; Ohdan, Hideki

    2016-01-01

    Liver transplantation (LT) is a considerably effective treatment for patients with end-stage hepatitis B virus (HBV)-related liver disease. However, HBV infection often recurs after LT without prophylaxis. Since the 1990s, the treatment for preventing HBV reinfection after LT has greatly progressed with the introduction of hepatitis B immunoglobulin (HBIG) and nucleos(t)ide analogues (NAs), resulting in improved patient survival. The combination therapy consisting of high-dose HBIG and lamivudine is highly efficacious for preventing the recurrence of HBV infection after LT and became the standard prophylaxis for HBV recurrence. However, mainly due to the high cost of HBIG treatment, an alternative protocol for reducing the dose and duration of HBIG has been evaluated. Currently, combination therapy using low-dose HBIG and NAs is considered as the most efficacious and cost-effective prophylaxis for post-LT HBV reinfection. Recently, NA monotherapy and withdrawal of HBIG from combination therapy, along with the development of new, potent high genetic barrier NAs, have provided promising efficacy, especially for low-risk recipients. This review summarizes the prophylactic protocol and their efficacy including prophylaxis of de novo HBV infection from anti-HBc antibody-positive donors. In addition, challenging approaches such as discontinuation of all prophylaxis and active immunity through hepatitis B vaccination are discussed. PMID:26755868

  1. A Generalized Entropy Measure of Within-Host Viral Diversity for Identifying Recent HIV-1 Infections.

    PubMed

    Wu, Julia Wei; Patterson-Lomba, Oscar; Novitsky, Vladimir; Pagano, Marcello

    2015-10-01

    There is a need for incidence assays that accurately estimate HIV incidence based on cross-sectional specimens. Viral diversity-based assays have shown promises but are not particularly accurate. We hypothesize that certain viral genetic regions are more predictive of recent infection than others and aim to improve assay accuracy by using classification algorithms that focus on highly informative regions (HIRs).We analyzed HIV gag sequences from a cohort in Botswana. Forty-two subjects newly infected by HIV-1 Subtype C were followed through 500 days post-seroconversion. Using sliding window analysis, we screened for genetic regions within gag that best differentiate recent versus chronic infections. We used both nonparametric and parametric approaches to evaluate the discriminatory abilities of sequence regions. Segmented Shannon Entropy measures of HIRs were aggregated to develop generalized entropy measures to improve prediction of recency. Using logistic regression as the basis for our classification algorithm, we evaluated the predictive power of these novel biomarkers and compared them with recently reported viral diversity measures using area under the curve (AUC) analysis.Change of diversity over time varied across different sequence regions within gag. We identified the top 50% of the most informative regions by both nonparametric and parametric approaches. In both cases, HIRs were in more variable regions of gag and less likely in the p24 coding region. Entropy measures based on HIRs outperformed previously reported viral-diversity-based biomarkers. These methods are better suited for population-level estimation of HIV recency.The patterns of diversification of certain regions within the gag gene are more predictive of recency of infection than others. We expect this result to apply in other HIV genetic regions as well. Focusing on these informative regions, our generalized entropy measure of viral diversity demonstrates the potential for improving

  2. A Generalized Entropy Measure of Within-Host Viral Diversity for Identifying Recent HIV-1 Infections

    PubMed Central

    Wu, Julia Wei; Patterson-Lomba, Oscar; Novitsky, Vladimir; Pagano, Marcello

    2015-01-01

    Abstract There is a need for incidence assays that accurately estimate HIV incidence based on cross-sectional specimens. Viral diversity-based assays have shown promises but are not particularly accurate. We hypothesize that certain viral genetic regions are more predictive of recent infection than others and aim to improve assay accuracy by using classification algorithms that focus on highly informative regions (HIRs). We analyzed HIV gag sequences from a cohort in Botswana. Forty-two subjects newly infected by HIV-1 Subtype C were followed through 500 days post-seroconversion. Using sliding window analysis, we screened for genetic regions within gag that best differentiate recent versus chronic infections. We used both nonparametric and parametric approaches to evaluate the discriminatory abilities of sequence regions. Segmented Shannon Entropy measures of HIRs were aggregated to develop generalized entropy measures to improve prediction of recency. Using logistic regression as the basis for our classification algorithm, we evaluated the predictive power of these novel biomarkers and compared them with recently reported viral diversity measures using area under the curve (AUC) analysis. Change of diversity over time varied across different sequence regions within gag. We identified the top 50% of the most informative regions by both nonparametric and parametric approaches. In both cases, HIRs were in more variable regions of gag and less likely in the p24 coding region. Entropy measures based on HIRs outperformed previously reported viral-diversity-based biomarkers. These methods are better suited for population-level estimation of HIV recency. The patterns of diversification of certain regions within the gag gene are more predictive of recency of infection than others. We expect this result to apply in other HIV genetic regions as well. Focusing on these informative regions, our generalized entropy measure of viral diversity demonstrates the potential for

  3. Hepatitis A viral load in relation to severity of the infection.

    PubMed

    Fujiwara, Keiichi; Kojima, Hiroshige; Yasui, Shin; Okitsu, Koichiro; Yonemitsu, Yutaka; Omata, Masao; Yokosuka, Osamu

    2011-02-01

    A correlation between hepatitis A virus (HAV) genomes and the clinical severity of hepatitis A has not been established. The viral load in sera of hepatitis A patients was examined to determine the possible association between hepatitis A severity and HAV replication. One hundred sixty-four serum samples from 91 Japanese patients with sporadic hepatitis A, comprising 11 patients with fulminant hepatitis, 10 with severe acute hepatitis, and 70 with self-limited acute hepatitis, were tested for HAV RNA. The sera included 83 serial samples from 20 patients. Viral load was measured by real-time RT-PCR. The detection rates of HAV RNA from fulminant, severe acute, and acute hepatitis were 10/11 (91%), 10/10 (100%), and 55/70 (79%), respectively. Mean values of HAV RNA at admission were 3.48 ± 1.30 logcopies/ml in fulminant, 4.19 ± 1.03 in severe acute, and 2.65 ± 1.64 in acute hepatitis. Patients with severe infection such as fulminant hepatitis and severe acute hepatitis had higher initial viral load than patients with less severe infection (P < 0.001). Viremia persisted for 14.2 ± 5.8 days in patients with severe infection and 21.4 ± 10.6 days in those with acute hepatitis after clinical onset (P = 0.19). HAV RNA was detectable quantitatively in the majority of the sera of hepatitis A cases during the early convalescent phase by real-time PCR. Higher initial viral replication was found in severely infected patients. An excessive host immune response might follow, reducing the viral load rapidly as a result of the destruction of large numbers of HAV-infected hepatocytes, and in turn severe disease might be induced. 2010 Wiley-Liss, Inc.

  4. Comorbidity and high viral load linked to clinical presentation of respiratory human bocavirus infection.

    PubMed

    Ghietto, Lucía María; Majul, Diego; Ferreyra Soaje, Patricia; Baumeister, Elsa; Avaro, Martín; Insfrán, Constanza; Mosca, Liliana; Cámara, Alicia; Moreno, Laura Beatriz; Adamo, Maria Pilar

    2015-01-01

    Human bocavirus (HBoV) is a new parvovirus associated with acute respiratory tract infection (ARTI). In order to evaluate HBoV significance as an agent of acute respiratory disease, we screened 1,135 respiratory samples from children and adults with and without symptoms during two complete calendar years. HBoV1 prevalence in patients with ARTI was 6.33 % in 2011 and 11.64 % in 2012, including neonatal and adult patients. HBoV1 was also detected in 3.77 % of asymptomatic individuals. The co-detection rate was 78.1 %. Among children, 87 % were clinically diagnosed with lower respiratory infection (no significant differences between patients with and without coinfection), and 31 % exhibited comorbidities. Pediatric patients with comorbidities were significantly older than patients without comorbidities. Patients with ARTI had either high or low viral load, while controls had only low viral load, but there were no clinical differences between patients with high or low viral load. In conclusion, we present evidence of the pathogenic potential of HBoV1 in young children with ARTI. Since patients with HBoV1-single infection are not significantly different from those with coinfection with respect to clinical features, the virus can be as pathogenic by itself as other respiratory agents are. Furthermore, an association between high HBoV1 load and disease could not be demonstrated in this study, but all asymptomatic individuals had low viral loads. Also, children with comorbidities are susceptible to HBoV1 infection at older ages than previously healthy children. Thus, the clinical presentation of infection may occur depending on both viral load and the particular interaction between the HBoV1 and the host.

  5. Genome-Wide Identification of Susceptibility Alleles for Viral Infections through a Population Genetics Approach

    PubMed Central

    Fumagalli, Matteo; Pozzoli, Uberto; Cagliani, Rachele; Comi, Giacomo P.; Bresolin, Nereo

    2010-01-01

    Viruses have exerted a constant and potent selective pressure on human genes throughout evolution. We utilized the marks left by selection on allele frequency to identify viral infection-associated allelic variants. Virus diversity (the number of different viruses in a geographic region) was used to measure virus-driven selective pressure. Results showed an excess of variants correlated with virus diversity in genes involved in immune response and in the biosynthesis of glycan structures functioning as viral receptors; a significantly higher than expected number of variants was also seen in genes encoding proteins that directly interact with viral components. Genome-wide analyses identified 441 variants significantly associated with virus-diversity; these are more frequently located within gene regions than expected, and they map to 139 human genes. Analysis of functional relationships among genes subjected to virus-driven selective pressure identified a complex network enriched in viral products-interacting proteins. The novel approach to the study of infectious disease epidemiology presented herein may represent an alternative to classic genome-wide association studies and provides a large set of candidate susceptibility variants for viral infections. PMID:20174570

  6. Rapid host immune response and viral dynamics in herpes simplex virus-2 infection

    PubMed Central

    Schiffer, Joshua T; Corey, Lawrence

    2014-01-01

    Herpes Simplex Virus-2 (HSV-2) is episodically shed throughout the human genital tract. While high viral load correlates with development of genital ulcers, shedding also commonly occurs even when ulcers are not present, allowing for silent transmission during coitus and contributing to high seroprevalence of HSV-2 worldwide. Frequent viral reactivation occurs despite diverse and complementary host and viral mechanisms within ganglionic tissue that predispose towards latency, suggesting that viral replication may be constantly occurring in a small minority of neurons within the ganglia. Within genital mucosa, the in vivo expansion and clearance rates of HSV-2 are extremely rapid. Resident dendritic cells and memory HSV-specific T cells persist at prior sites of genital tract reactivation, and in conjunction with prompt innate recognition of infected cells, lead to rapid containment of infected cells. Shedding episodes vary greatly in duration and severity within a single person over time: this heterogeneity appears best explained by variation in the densities of host immunity across the genital tract. The fact that immune responses usually control viral replication in genital skin prior to development of lesions provides optimism that enhancing such responses could lead to effective vaccines and immunotherapies. PMID:23467247

  7. Hepatitis B Infection, Viral Load and Resistance in HIV-Infected Patients in Mozambique and Zambia

    PubMed Central

    Wandeler, Gilles; Musukuma, Kalo; Zürcher, Samuel; Vinikoor, Michael J.; Llenas-García, Jara; Aly, Mussa M.; Mulenga, Lloyd; Chi, Benjamin H.; Ehmer, Jochen; Hobbins, Michael A.; Bolton-Moore, Carolyn; Hoffmann, Christopher J.; Egger, Matthias

    2016-01-01

    Background Few data on the virological determinants of hepatitis B virus (HBV) infection are available from southern Africa. Methods We enrolled consecutive HIV-infected adult patients initiating antiretroviral therapy (ART) at two urban clinics in Zambia and four rural clinics in Northern Mozambique between May 2013 and August 2014. HBsAg screening was performed using the Determine® rapid test. Quantitative real-time PCR and HBV sequencing were performed in HBsAg-positive patients. Risk factors for HBV infection were evaluated using Chi-square and Mann-Whitney tests and associations between baseline characteristics and high level HBV replication explored in multivariable logistic regression. Results Seventy-eight of 1,032 participants in Mozambique (7.6%, 95% confidence interval [CI]: 6.1–9.3) and 90 of 797 in Zambia (11.3%, 95% CI: 9.3–13.4) were HBsAg-positive. HBsAg-positive individuals were less likely to be female compared to HBsAg-negative ones (52.3% vs. 66.1%, p<0.001). Among 156 (92.9%) HBsAg-positive patients with an available measurement, median HBV viral load was 13,645 IU/mL (interquartile range: 192–8,617,488 IU/mL) and 77 (49.4%) had high values (>20,000 UI/mL). HBsAg-positive individuals had higher levels of ALT and AST compared to HBsAg-negative ones (both p<0.001). In multivariable analyses, male sex (adjusted odds ratio: 2.59, 95% CI: 1.22–5.53) and CD4 cell count below 200/μl (2.58, 1.20–5.54) were associated with high HBV DNA. HBV genotypes A1 (58.8%) and E (38.2%) were most prevalent. Four patients had probable resistance to lamivudine and/or entecavir. Conclusion One half of HBsAg-positive patients demonstrated high HBV viremia, supporting the early initiation of tenofovir-containing ART in HIV/HBV-coinfected adults. PMID:27032097

  8. The ins and outs of eukaryotic viruses: Knowledge base and ontology of a viral infection

    PubMed Central

    Hulo, Chantal; Masson, Patrick; de Castro, Edouard; Auchincloss, Andrea H.; Foulger, Rebecca; Poux, Sylvain; Lomax, Jane; Bougueleret, Lydie; Xenarios, Ioannis

    2017-01-01

    Viruses are genetically diverse, infect a wide range of tissues and host cells and follow unique processes for replicating themselves. All these processes were investigated and indexed in ViralZone knowledge base. To facilitate standardizing data, a simple ontology of viral life-cycle terms was developed to provide a common vocabulary for annotating data sets. New terminology was developed to address unique viral replication cycle processes, and existing terminology was modified and adapted. The virus life-cycle is classically described by schematic pictures. Using this ontology, it can be represented by a combination of successive terms: “entry”, “latency”, “transcription”, “replication” and “exit”. Each of these parts is broken down into discrete steps. For example Zika virus “entry” is broken down in successive steps: “Attachment”, “Apoptotic mimicry”, “Viral endocytosis/ macropinocytosis”, “Fusion with host endosomal membrane”, “Viral factory”. To demonstrate the utility of a standard ontology for virus biology, this work was completed by annotating virus data in the ViralZone, UniProtKB and Gene Ontology databases. PMID:28207819

  9. The ins and outs of eukaryotic viruses: Knowledge base and ontology of a viral infection.

    PubMed

    Hulo, Chantal; Masson, Patrick; de Castro, Edouard; Auchincloss, Andrea H; Foulger, Rebecca; Poux, Sylvain; Lomax, Jane; Bougueleret, Lydie; Xenarios, Ioannis; Le Mercier, Philippe

    2017-01-01

    Viruses are genetically diverse, infect a wide range of tissues and host cells and follow unique processes for replicating themselves. All these processes were investigated and indexed in ViralZone knowledge base. To facilitate standardizing data, a simple ontology of viral life-cycle terms was developed to provide a common vocabulary for annotating data sets. New terminology was developed to address unique viral replication cycle processes, and existing terminology was modified and adapted. The virus life-cycle is classically described by schematic pictures. Using this ontology, it can be represented by a combination of successive terms: "entry", "latency", "transcription", "replication" and "exit". Each of these parts is broken down into discrete steps. For example Zika virus "entry" is broken down in successive steps: "Attachment", "Apoptotic mimicry", "Viral endocytosis/ macropinocytosis", "Fusion with host endosomal membrane", "Viral factory". To demonstrate the utility of a standard ontology for virus biology, this work was completed by annotating virus data in the ViralZone, UniProtKB and Gene Ontology databases.

  10. Restricted infectivity of ecotropic type C retroviruses in mouse teratocarcinoma cells: studies on viral DNA intermediates

    SciTech Connect

    Yang, W.K.; d'Auriol, L.; Yang, D.M.; Kiggans, J.O. Jr.; Ou, C.; Peries, J.; Emanoil-Ravicovitch, R.

    1980-01-01

    Replication of Gross strain N-tropic type C retrovirus was markedly restricted in a pluripotential undifferentiated embryonal cell line (PCC/sub 4/) of murine teratocarcinoma, whereas the same virus could cause productive infection in a myoblast-derived differentiated line (PCD/sub 1/) of the same tumor origin. To investigate the restriction mechanism, we compared the initial viral DNA formation in these two cell lines. Analyses by means of a modified Hirt extraction procedure and a modified Southern gel transfer method indicated that PCC/sub 4/ and PCD/sub 1/ cells supported the synthesis of viral DNA intermediates after inoculation of the Gross virus. In both cells a linear DNA duplex (form III viral DNA) appeared at 4 h, reached a maximal level at 8 to 9 h, and declined rapidly thereafter, while two closed-circular supercoiled DNA duplexes (form I viral DNA) showed their appearance, increase and decline in the 8 to 24 h period. During the period from 34 to 78 h after virus inoculation, another burst of viral DNA synthesis occurred in PCD/sub 1/ cells, presumably due to secondary virus infection, while at this period both form III and form I viral DNAs became undetectable in PCC/sub 4/ cells. The Hirt supernatant DNAs prepared from PCD/sub 1/ and PCC/sub 4/ cells 10 h after virus inoculation were equally infectious for NIH3T3 cells in a DNA transfection assay. Both PCD/sub 1/ and PCC/sub 4/ cells were very poor recipients for DNA transfection, although one positive result with PCD/sub 1/ cells might suggest a difference between the two cell types in this aspect. These results indicate that restriction of type C retrovirus in undifferentiated embryonal carcinoma cells occurs at a step subsequent to formation and maturation of viral DNA intermediates.

  11. Lytic viral infection of bacterioplankton in deep waters of the western Pacific Ocean

    NASA Astrophysics Data System (ADS)

    Li, Y.; Luo, T.; Sun, J.; Cai, L.; Jiao, N.; Zhang, R.

    2013-12-01

    As the most abundant biological entities in the ocean, viruses can influence host mortality and nutrients recycling mainly through lytic infection. Yet ecological characteristics of virioplankton and viral impacts on host mortality and biogeochemical cycling in the deep sea are largely unknown. In present study, viral abundance and lytic infection was investigated throughout the water column in the western Pacific Ocean. Both the prokaryotic and viral abundance and production showed a significantly decreasing trend from epipelagic to meso- and bathypelagic waters. Viral abundance decreased from 0.36-1.05 × 1010 particles L-1 to 0.43-0.80 × 109 particles L-1, while the virus : prokaryote ratio varied from 7.21-16.23 to 2.45-23.40, at surface and 2000 m depth, respectively. The lytic viral production rates in surface and 2000 m waters were, averagely, 1.03 × 1010 L-1 day-1 and 5.74 × 108 L-1 day-1, respectively. Relatively high percentages of prokaryotic cells lysed by virus in 1000 m and 2000 m were observed, suggesting a significant contribution of viruses to prokaryotic mortality in deep ocean. The carbon released by viral lysis in deep western Pacific Ocean waters was from 0.03 to 2.32 μg C L-1 day-1. Our findings demonstrated a highly dynamic and active viral population in the deep western Pacific Ocean and suggested that virioplankton play an important role in the microbial loop and subsequently biogeochemical cycling in deep oceans.

  12. Lytic viral infection of bacterioplankton in deep waters of the western Pacific Ocean

    NASA Astrophysics Data System (ADS)

    Li, Y.; Luo, T.; Sun, J.; Cai, L.; Liang, Y.; Jiao, N.; Zhang, R.

    2014-05-01

    As the most abundant biological entities in the ocean, viruses influence host mortality and nutrient recycling mainly through lytic infection. Yet, the ecological characteristics of virioplankton and viral impacts on host mortality and biogeochemical cycling in the deep sea are largely unknown. In the present study, viral abundance and lytic infection were investigated throughout the water column in the western Pacific Ocean. Both the prokaryotic and viral abundance and production showed a significantly decreasing trend from epipelagic to meso- and bathypelagic waters. Viral abundance decreased from 0.36-1.05 × 1010 particles L-1 to 0.43-0.80 × 109 particles L-1, while the virus : prokaryote ratio varied from 7.21 to 16.23 to 2.45-23.40, at the surface and 2000 m, respectively. Lytic viral production rates in surface and 2000 m waters were, on average, 1.03 × 1010 L-1 day-1 and 5.74 × 108 L-1 day-1. Relatively high percentages of prokaryotic cells lysed by viruses at 1000 and 2000 m were observed, suggesting a significant contribution of viruses to prokaryotic mortality in the deep ocean. The carbon released by viral lysis in deep western Pacific Ocean waters was from 0.03 to 2.32 μg C L-1 day-1. Our findings demonstrated a highly dynamic and active viral population in these deep waters and suggested that virioplankton play an important role in the microbial loop and subsequently biogeochemical cycling in deep oceans.

  13. IL-17-induced pulmonary pathogenesis during respiratory viral infection and exacerbation of allergic disease.

    PubMed

    Mukherjee, Sumanta; Lindell, Dennis M; Berlin, Aaron A; Morris, Susan B; Shanley, Thomas P; Hershenson, Marc B; Lukacs, Nicholas W

    2011-07-01

    Severe respiratory syncytial virus (RSV) infections are characterized by airway epithelial cell damage, mucus hypersecretion, and Th2 cytokine production. Less is known about the role of IL-17. We observed increased IL-6 and IL-17 levels in tracheal aspirate samples from severely ill infants with RSV infection. In a mouse model of RSV infection, time-dependent increases in pulmonary IL-6, IL-23, and IL-17 expression were observed. Neutralization of IL-17 during infection and observations from IL-17(-/-) knockout mice resulted in significant inhibition of mucus production during RSV infection. RSV-infected animals treated with anti-IL-17 had reduced inflammation and decreased viral load, compared with control antibody-treated mice. Blocking IL-17 during infection resulted in significantly increased RSV-specific CD8 T cells. Factors associated with CD8 cytotoxic T lymphocytes, T-bet, IFN-γ, eomesodermin, and granzyme B were significantly up-regulated after IL-17 blockade. Additionally, in vitro analyses suggest that IL-17 directly inhibits T-bet, eomesodermin, and IFN-γ in CD8 T cells. The role of IL-17 was also investigated in RSV-induced exacerbation of allergic airway responses, in which neutralization of IL-17 led to a significant decrease in the exacerbated disease, including reduced mucus production and Th2 cytokines, with decreased viral proteins. Taken together, our data demonstrate that IL-17 plays a pathogenic role during RSV infections.

  14. Rapid diagnosis of goose viral infections by multiplex PCR.

    PubMed

    Chen, Zongyan; Li, Chuanfeng; Li, Guoxin; Yu, Hai; Jiang, Yifeng; Yan, Liping; Meng, Chunchun; Zhou, Yanjun; Tong, Guangzhi; Liu, Guangqing

    2013-08-01

    Goose parvovirus (GPV), newcastle disease virus (NDV), goose herpesvirus (GHV) and goose adenovirus (GAV) are considered collectively to be four of the most important and widespread viruses of geese. Because all of these viruses cause similar pathological changes, histological differentiation among these viruses is difficult. A reliable, specific and sensitive multiplex PCR (mPCR) assay was developed for the combined detection of GPV, NDV, GHV and GAV in clinical samples of geese. Using the mPCR technique, single infections with GPV (28/76; 36.8%), NDV (9/76; 11.8%), GHV (3/76; 3.9%) and GAV (12/76; 15.8%) were identified in the samples; co-infections with GAV and either GPV or NDV (31.6%; 24/76) were also identified with this approach. The results for all of the samples tested were the same in both the uPCR and mPCR systems. The mPCR approach is considered to be useful for routine molecular diagnosis and epidemiological applications in geese.

  15. Emerging therapies for herpes viral infections (types 1 - 8).

    PubMed

    Chakrabarty, Arun; Pang, Katie R; Wu, Jashin J; Narvaez, Julio; Rauser, Michael; Huang, David B; Beutner, Karl R; Tyring, Stephen K

    2004-11-01

    There are eight members of the herpesviridae family: herpes simplex virus-1 (HSV-1), HSV-2, varicella-zoster virus, Epstein-Barr virus, cytomegalovirus, human herpes virus-6, human herpes virus-7 and human herpes virus-8. The diseases caused by viruses of the herpesviridae family are treated with and managed by systemic and topical antiviral therapies and immunomodulating drugs. Because these viruses establish a latent state in hosts, antiherpetic agents, such as nucleoside analogues, only control symptoms of disease or prevent outbreaks, and cannot cure the infections. There is a need for treatments that require less frequent dosing, can be taken even when lesions are more advanced than the first signs or symptoms, and can treat resistant strains of the viruses without the toxicities of existing therapies. Immunomodulating agents, such as resiquimod, can act on the viruses indirectly by inducing host production of cytokines, and can thereby reduce recurrences of herpes. The new helicase primase inhibitors, which are the first non-nucleoside antiviral compounds, are being investigated for treatment of HSV disease, including infections resistant to existing therapy.

  16. PD-L1-expressing dendritic cells contribute to viral resistance during acute HSV-1 infection.

    PubMed

    Bryant-Hudson, Katie M; Carr, Daniel J J

    2012-01-01

    The inhibitory receptor, Programmed Death 1 (PD-1), and its ligands (PD-L1/PD-L2) are thought to play a role in immune surveillance during chronic viral infection. The contribution of the receptor/ligand pair during an acute infection is less understood. To determine the role of PD-L1 and PD-L2 during acute ocular herpes simplex virus type 1 (HSV-1) infection, HSV-1-infected mice administered neutralizing antibody to PD-L1 or PD-L2 were assessed for viral burden and host cellular immune responses. Virus titers were elevated in cornea and trigeminal ganglia (TG) of anti-PD-L1-treated mice which corresponded with a reduced number of CD80-expressing dendritic cells, PD-L1⁺ dendritic cells, and HSV-1-specific CD8⁺ T cells within the draining (mandibular) lymph node (MLN). In contrast, anti-PD-L2 treatment had no effect on viral replication or changes in the MLN population. Notably, analysis of CD11c-enriched MLN cells from anti-PD-L1-treated mice revealed impaired functional capabilities. These studies indicate PD-L1-expressing dendritic cells are important for antiviral defense during acute HSV-1 infection.

  17. 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.

  18. Type I IFN promotes NK cell expansion during viral infection by protecting NK cells against fratricide.

    PubMed

    Madera, Sharline; Rapp, Moritz; Firth, Matthew A; Beilke, Joshua N; Lanier, Lewis L; Sun, Joseph C

    2016-02-08

    Type I interferon (IFN) is crucial in host antiviral defense. Previous studies have described the pleiotropic role of type I IFNs on innate and adaptive immune cells during viral infection. Here, we demonstrate that natural killer (NK) cells from mice lacking the type I IFN-α receptor (Ifnar(-/-)) or STAT1 (which signals downstream of IFNAR) are defective in expansion and memory cell formation after mouse cytomegalovirus (MCMV) infection. Despite comparable proliferation, Ifnar(-/-) NK cells showed diminished protection against MCMV infection and exhibited more apoptosis compared with wild-type NK cells. Furthermore, we show that Ifnar(-/-) NK cells express increased levels of NK group 2 member D (NKG2D) ligands during viral infection and are susceptible to NK cell-mediated fratricide in a perforin- and NKG2D-dependent manner. Adoptive transfer of Ifnar(-/-) NK cells into NK cell-deficient mice reverses the defect in survival and expansion. Our study reveals a novel type I IFN-dependent mechanism by which NK cells evade mechanisms of cell death after viral infection.

  19. Type I IFN promotes NK cell expansion during viral infection by protecting NK cells against fratricide

    PubMed Central

    Madera, Sharline; Rapp, Moritz; Firth, Matthew A.; Beilke, Joshua N.; Lanier, Lewis L.

    2016-01-01

    Type I interferon (IFN) is crucial in host antiviral defense. Previous studies have described the pleiotropic role of type I IFNs on innate and adaptive immune cells during viral infection. Here, we demonstrate that natural killer (NK) cells from mice lacking the type I IFN-α receptor (Ifnar−/−) or STAT1 (which signals downstream of IFNAR) are defective in expansion and memory cell formation after mouse cytomegalovirus (MCMV) infection. Despite comparable proliferation, Ifnar−/− NK cells showed diminished protection against MCMV infection and exhibited more apoptosis compared with wild-type NK cells. Furthermore, we show that Ifnar−/− NK cells express increased levels of NK group 2 member D (NKG2D) ligands during viral infection and are susceptible to NK cell–mediated fratricide in a perforin- and NKG2D-dependent manner. Adoptive transfer of Ifnar−/− NK cells into NK cell–deficient mice reverses the defect in survival and expansion. Our study reveals a novel type I IFN–dependent mechanism by which NK cells evade mechanisms of cell death after viral infection. PMID:26755706

  20. Singapore grouper iridovirus protein VP088 is essential for viral infectivity

    PubMed Central

    Yuan, Yongming; Wang, Yunzhi; Liu, Qizhi; Zhu, Feng; Hong, Yunhan

    2016-01-01

    Viral infection is a great challenge in healthcare and agriculture. The Singapore grouper iridovirus (SGIV) is highly infectious to numerous marine fishes and increasingly threatens mariculture and wildlife conservation. SGIV intervention is not available because little is known about key players and their precise roles in SGVI infection. Here we report the precise role of VP088 as a key player in SGIV infection. VP088 was verified as an envelope protein encoded by late gene orf088. We show that SGIV could be neutralized with an antibody against VP088. Depletion or deletion of VP088 significantly suppresses SGIV infection without altering viral gene expression and host responses. By precisely quantifying the genome copy numbers of host cells and virions, we reveal that VP088 deletion dramatically reduces SGIV infectivity through inhibiting virus entry without altering viral pathogenicity, genome stability and replication and progeny virus release. These results pinpoint that VP088 is a key player in SGIV entry and represents an ideal target for SGIV intervention. PMID:27498856

  1. Restitution of infectivity to spikeless vesicular stomatitis virus by solubilized viral components.

    PubMed

    Bishop, D H; Repik, P; Obijeski, J F; Moore, N F; Wagner, R R

    1975-07-01

    Noninfectious spikeless particles have been obtained from vesicular stomatitis virus (VSV, Indiana serotype) by bromelain or Pronase treatment. They lack the viral glycoprotein (G) but contain all the other viral components (RNA, lipid, and other structural proteins). Triton-solubilized VSV-Indiana glycoprotein preparations, containing the viral G protein as well as lipids (including phospholipids), have been extracted from whole virus preparations, freed from the majority of the detergent, and used to restore infectivity to spikeless VSV. The infectivity of such particles has been found to be enhanced by poly-L-ornithine but inhibited by Trition or homologous antiserum pretreatment. Heat-denatured glycoprotein preparations were not effective in restoring the infectivity to spikeless VSV. Heterologous glycoprotein preparations from the serologically distinct VSV-New Jersey serotype were equally capable of making infectious entities with VSV-Indiana spikeless particles, and the infectivity of these structures was inhibited by VSV-New Jersey antiserum but not by VSV-Indiana antiserum. Purified, detergent-free glycoprotein selectively solubilized from VSV-Indiana by the dialyzable detergent, octylglucoside, also restored infectivity of spikeless virions of VSV-Indiana and VSV-New Jersey.

  2. Detection of high biliary and fecal viral loads in patients with chronic hepatitis C virus infection.

    PubMed

    Monrroy, Hugo; Angulo, Jenniffer; Pino, Karla; Labbé, Pilar; Miquel, Juan Francisco; López-Lastra, Marcelo; Soza, Alejandro

    2017-05-01

    The life cycle of the hepatitis C virus (HCV) is closely associated with lipid metabolism. Recently, NPC1L1 (a cholesterol transporter) has been reported to function as an HCV receptor. This receptor is expressed in the hepatocyte canalicular membrane and in the intestine; serving as a key transporter for the cholesterol enterohepatic cycle. We hypothesized that HCV might have a similar cycle, so we aimed to study the presence of HCV in bile and stools of infected patients. Blood, feces, and duodenal bile samples were collected from patients infected with HCV. The biliary viral load was normalized to the bile salt concentration of each sample and the presence of HCV core protein was also evaluated. A total of 12 patients were recruited. HCV RNA was detected in the bile from ten patients. The mean viral load was 2.5log10IU/60mg bile salt. In the stool samples, HCV RNA was detected in ten patients (mean concentration 2.7log10IU/g of feces). HCV RNA is readily detectable and is present at relatively high concentrations in the bile and stool samples of infected patients. This may be relevant as a source of infection in men who have sex with men. Biliary HCV secretion may perhaps play a role in the persistence of viral infection via an enterohepatic cycle of the virus or intrahepatic spread. Copyright © 2017 Elsevier España, S.L.U., AEEH y AEG. All rights reserved.

  3. Therapeutic doses of irradiation activate viral transcription and induce apoptosis in HIV-1 infected cells.

    PubMed

    Iordanskiy, Sergey; Van Duyne, Rachel; Sampey, Gavin C; Woodson, Caitlin M; Fry, Kelsi; Saifuddin, Mohammed; Guo, Jia; Wu, Yuntao; Romerio, Fabio; Kashanchi, Fatah

    2015-11-01

    The highly active antiretroviral therapy reduces HIV-1 RNA in plasma to undetectable levels. However, the virus continues to persist in the long-lived resting CD4(+) T cells, macrophages and astrocytes which form a viral reservoir in infected individuals. Reactivation of viral transcription is critical since the host immune response in combination with antiretroviral therapy may eradicate the virus. Using the chronically HIV-1 infected T lymphoblastoid and monocytic cell lines, primary quiescent CD4(+) T cells and humanized mice infected with dual-tropic HIV-1 89.6, we examined the effect of various X-ray irradiation (IR) doses (used for HIV-related lymphoma treatment and lower doses) on HIV-1 transcription and viability of infected cells. Treatment of both T cells and monocytes with IR, a well-defined stress signal, led to increase of HIV-1 transcription, as evidenced by the presence of RNA polymerase II and reduction of HDAC1 and methyl transferase SUV39H1 on the HIV-1 promoter. This correlated with the increased GFP signal and elevated level of intracellular HIV-1 RNA in the IR-treated quiescent CD4(+) T cells infected with GFP-encoding HIV-1. Exposition of latently HIV-1infected monocytes treated with PKC agonist bryostatin 1 to IR enhanced transcription activation effect of this latency-reversing agent. Increased HIV-1 replication after IR correlated with higher cell death: the level of phosphorylated Ser46 in p53, responsible for apoptosis induction, was markedly higher in the HIV-1 infected cells following IR treatment. Exposure of HIV-1 infected humanized mice with undetectable viral RNA level to IR resulted in a significant increase of HIV-1 RNA in plasma, lung and brain tissues. Collectively, these data point to the use of low to moderate dose of IR alone or in combination with HIV-1 transcription activators as a potential application for the "Shock and Kill" strategy for latently HIV-1 infected cells.

  4. An integrated map of HIV-human protein complexes that facilitate viral infection.

    PubMed

    Emig-Agius, Dorothea; Olivieri, Kevin; Pache, Lars; Shih, Hsin Ling; Pustovalova, Olga; Bessarabova, Marina; Young, John A T; Chanda, Sumit K; Ideker, Trey

    2014-01-01

    Recent proteomic and genetic studies have aimed to identify a complete network of interactions between HIV and human proteins and genes. This HIV-human interaction network provides invaluable information as to how HIV exploits the host machinery and can be used as a starting point for further functional analyses. We integrated this network with complementary datasets of protein function and interaction to nominate human protein complexes with likely roles in viral infection. Based on our approach we identified a global map of 40 HIV-human protein complexes with putative roles in HIV infection, some of which are involved in DNA replication and repair, transcription, translation, and cytoskeletal regulation. Targeted RNAi screens were used to validate several proteins and complexes for functional impact on viral infection. Thus, our HIV-human protein complex map provides a significant resource of potential HIV-host interactions for further study.

  5. Viral infections of the lower respiratory tract: old viruses, new viruses, and the role of diagnosis.

    PubMed

    Pavia, Andrew T

    2011-05-01

    Viral infections of the lower respiratory tract cause an enormous disease burden in children, and the role of respiratory viruses in serious lower respiratory tract infections (LRTIs) in older adults is increasingly appreciated. Although viruses are responsible for a large proportion LRTIs, antibiotics are often prescribed. New diagnostic platforms have the potential to detect a wider range of established and newly discovered viruses with greater sensitivity. This will create additional challenges. Although it is clear that influenza, parainfluenza, respiratory syncytial virus, human metapneumovirus, and adenovirus are important causes of pneumonia, the role of rhinoviruses and some of the newly described viruses, including human coronaviruses and bocavirus, is harder to determine. Better diagnostic tests that establish the cause of LRTIs in children have the potential to both reduce overall antibiotic use and to improve the targeted use of antibiotics. In addition, rapid identification of viral infections can help control nosocomial transmission.

  6. Brain-resident memory T cells represent an autonomous cytotoxic barrier to viral infection

    PubMed Central

    Vincenti, Ilena; Wagner, Ingrid; Pinschewer, Daniel

    2016-01-01

    Tissue-resident memory T cells (TRM) persist at sites of prior infection and have been shown to enhance pathogen clearance by recruiting circulating immune cells and providing bystander activation. Here, we characterize the functioning of brain-resident memory T cells (bTRM) in an animal model of viral infection. bTRM were subject to spontaneous homeostatic proliferation and were largely refractory to systemic immune cell depletion. After viral reinfection in mice, bTRM rapidly acquired cytotoxic effector function and prevented fatal brain infection, even in the absence of circulating CD8+ memory T cells. Presentation of cognate antigen on MHC-I was essential for bTRM-mediated protective immunity, which involved perforin- and IFN-γ–dependent effector mechanisms. These findings identify bTRM as an organ-autonomous defense system serving as a paradigm for TRM functioning as a self-sufficient first line of adaptive immunity. PMID:27377586

  7. Viral Metagenomics on Animals as a Tool for the Detection of Zoonoses Prior to Human Infection?

    PubMed Central

    Temmam, Sarah; Davoust, Bernard; Berenger, Jean-Michel; Raoult, Didier; Desnues, Christelle

    2014-01-01

    Many human viral infections have a zoonotic, i.e., wild or domestic animal, origin. Several zoonotic viruses are transmitted to humans directly via contact with an animal or indirectly via exposure to the urine or feces of infected animals or the bite of a bloodsucking arthropod. If a virus is able to adapt and replicate in its new human host, human-to-human transmissions may occur, possibly resulting in an epidemic, such as the A/H1N1 flu pandemic in 2009. Thus, predicting emerging zoonotic infections is an important challenge for public health officials in the coming decades. The recent development of viral metagenomics, i.e., the characterization of the complete viral diversity isolated from an organism or an environment using high-throughput sequencing technologies, is promising for the surveillance of such diseases and can be accomplished by analyzing the viromes of selected animals and arthropods that are closely in contact with humans. In this review, we summarize our current knowledge of viral diversity within such animals (in particular blood-feeding arthropods, wildlife and domestic animals) using metagenomics and present its possible future application for the surveillance of zoonotic and arboviral diseases. PMID:24918293

  8. Amitraz and its metabolite modulate honey bee cardiac function and tolerance to viral infection.

    PubMed

    O'Neal, Scott T; Brewster, Carlyle C; Bloomquist, Jeffrey R; Anderson, Troy D

    2017-10-01

    The health and survival of managed honey bee (Apis mellifera) colonies are affected by multiple factors, one of the most important being the interaction between viral pathogens and infestations of the ectoparasitic mite Varroa destructor. Currently, the only effective strategy available for mitigating the impact of viral infections is the chemical control of mite populations. Unfortunately, the use of in-hive acaricides comes at a price, as they can produce sublethal effects that are difficult to quantify, but may ultimately be as damaging as the mites they are used to treat. The goal of this study was to investigate the physiological and immunological effects of the formamidine acaricide amitraz and its primary metabolite in honey bees. Using flock house virus as a model for viral infection, this study found that exposure to a formamidine acaricide may have a negative impact on the ability of honey bees to tolerate viral infection. Furthermore, this work has demonstrated that amitraz and its metabolite significantly alter honey bee cardiac function, most likely through interaction with octopamine receptors. The results suggest a potential drawback to the in-hive use of amitraz and raise intriguing questions about the relationship between insect cardiac function and disease tolerance. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Nuclear sensing of viral DNA, epigenetic regulation of herpes simplex virus infection, and innate immunity

    SciTech Connect

    Knipe, David M.

    2015-05-15

    Herpes simplex virus (HSV) undergoes a lytic infection in epithelial cells and a latent infection in neuronal cells, and epigenetic mechanisms play a major role in the differential gene expression under the two conditions. HSV viron DNA is not associated with histones but is rapidly loaded with heterochromatin upon entry into the cell. Viral proteins promote reversal of the epigenetic silencing in epithelial cells while the viral latency-associated transcript promotes additional heterochromatin in neuronal cells. The cellular sensors that initiate the chromatinization of foreign DNA have not been fully defined. IFI16 and cGAS are both essential for innate sensing of HSV DNA, and new evidence shows how they work together to initiate innate signaling. IFI16 also plays a role in the heterochromatinization of HSV DNA, and this review will examine how IFI16 integrates epigenetic regulation and innate sensing of foreign viral DNA to show how these two responses are related. - Highlights: • HSV lytic and latent gene expression is regulated differentially by epigenetic processes. • The sensors of foreign DNA have not been defined fully. • IFI16 and cGAS cooperate to sense viral DNA in HSV-infected cells. • IFI16 plays a role in both innate sensing of HSV DNA and in restricting its expression.

  10. High Prevalence of Human Metapneumovirus Infection in Young Children and Genetic Heterogeneity of the Viral Isolates

    PubMed Central

    Viazov, S.; Ratjen, F.; Scheidhauer, R.; Fiedler, M.; Roggendorf, M.

    2003-01-01

    RNA of the newly identified human metapneumovirus (HMPV) was detected in nasopharyngeal aspirates of 11 of 63 (17.5%) young children with respiratory tract disease. Markers of infection caused by another member of the Pneumovirinae subfamily of the family Paramyxoviridae, respiratory syncytial virus (RSV), were identified in 15 of these patients (23.8%). Three patients were simultaneously infected with HMPV and RSV. Studies of the clinical characteristics of HMPV-infected children did not reveal any difference between HMPV-infected patients and a control population of RSV-infected patients with regard to disease severity, but the duration of symptoms was significantly shorter for HMPV-infected patients. Phylogenetic analysis of the amplified viral genome fragments confirmed the existence and simultaneous circulation within one epidemic season of HMPV isolates belonging to two genetic lineages. PMID:12843040

  11. Etiology, seasonality, and clinical characterization of viral respiratory infections among hospitalized children in Beirut, Lebanon.

    PubMed

    Finianos, Mayda; Issa, Randi; Curran, Martin D; Afif, Claude; Rajab, Maryam; Irani, Jihad; Hakimeh, Noha; Naous, Amal; Hajj, Marie-Joelle; Hajj, Pierre; El Jisr, Tamima; El Chaar, Mira

    2016-11-01

    Acute respiratory tract viral infections occur worldwide and are one of the major global burdens of diseases in children. The aim of this study was to determine the viral etiology of respiratory infections in hospitalized children, to understand the viral seasonality in a major Lebanese hospital, and to correlate disease severity and the presence of virus. Over a 1-year period, nasal and throat swabs were collected from 236 pediatric patients, aged 16-year old or less and hospitalized for acute respiratory illness. Samples collected were tested for the presence of 17 respiratory viruses using multiplex real-time RT-PCR. Pathogens were identified in 165 children (70%) and were frequently observed during fall and winter seasons. Co-infection was found in 37% of positive samples. The most frequently detected pathogens were human Rhinovirus (hRV, 23%), Respiratory Syncytial Virus (RSV, 19%), human Bocavirus (hBov, 15%), human Metapneumovirus (hMPV, 10%), and human Adenovirus (hAdV, 10%). A total of 48% of children were diagnosed with bronchiolitis and 25% with pneumonia. While bronchiolitis was often caused by RSV single virus infection and hAdV/hBoV coinfection, pneumonia was significantly associated with hBoV and HP1V1 infections. No significant correlation was observed between a single viral etiology infection and a specific clinical symptom. This study provides relevant facts on the circulatory pattern of respiratory viruses in Lebanon and the importance of using PCR as a useful tool for virus detection. Early diagnosis at the initial time of hospitalization may reduce the spread of the viruses in pediatric units. J. Med. Virol. 88:1874-1881, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  12. Corneal endothelial cells activate innate and acquired arm of anti-viral responses after cytomegalovirus infection.

    PubMed

    Miyazaki, Dai; Uotani, Ryu; Inoue, Michiko; Haruki, Tomoko; Shimizu, Yumiko; Yakura, Keiko; Yamagami, Satoru; Suzutani, Tatsuo; Hosogai, Mayumi; Isomura, Hiroki; Inoue, Yoshitsugu

    2017-08-01

    Infection of the corneal endothelial cells by human cytomegalovirus (CMV) is an important cause of corneal endotheliitis. CMV endotheliitis is difficult to completely cure and relapses are frequent. This can cause blinding corneal bullous keratopathy. However, the pathogenesis of CMV endotheliitis remains undetermined. To understand the immunopathology of endotheliitis, we examined how corneal endothelial cells prime the anti-viral immunity after CMV infection based on global transcriptional responses. To accomplish this, human corneal endothelial (HCEn) cells were infected with CMV, and the global transcriptional responses were determined by microarray analyses for primary anti-viral responses using network analysis. Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and protein array analyses were used to examine whether anti-viral cytokines were induced, i.e., to determine whether innate immune responses were activated. To examine whether priming of acquired immune response was activated, CMV-infected HCEn cells were co-cultured with allogeneic CD8(+) T cells from CMV seropositive donors and tested for priming activity for the CD8(+) effector T cells by measuring interferon-γ secretion. The CMV-induced responses of HCEn cells were characterized by type I interferon and pattern recognition receptor pathways which represent innate immune priming. The global transcriptional activation was specifically associated with antigen presentation with the antimicrobial response functions. Protein array analyses indicated a significant increase in the secretion of anti-viral inflammatory cytokines including CXCL10 as innate immune responses. When HCEn cells were examined to determine whether CMV infection activated anti-viral acquired immunity, CMV-infected HCEn cells directly stimulated the proliferation of CD8(+) T cells from CMV-seropositive donors, and pp65 viral epitope induced interferon-γ secretion from the CD8(+) T cells. We conclude that CMV-infected

  13. Sputnik, a virophage infecting the viral domain of life.

    PubMed

    Desnues, Christelle; Boyer, Mickaël; Raoult, Didier

    2012-01-01

    This chapter discusses the astonishing discovery of the Sputnik virophage, a new virus infecting giant viruses of the genera Mimivirus and Mamavirus. While other virophages have also since been described, this chapter focuses mainly on Sputnik, which is the best described. We detail the general properties of the virophage life cycle, as well as its hosts, genomic characteristics, ecology, and origin. In addition to genetic, phylogenetic, and structural evidence, the existence of virophages has deeply altered our view of the tripartite division of life to include the addition of a fourth domain constituted of the nucleocytoplasmic large DNA viruses, an important point that is discussed. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. The Role of F-Box Proteins during Viral Infection

    PubMed Central

    Correa, Régis Lopes; Bruckner, Fernanda Prieto; de Souza Cascardo, Renan; Alfenas-Zerbini, Poliane

    2013-01-01

    The F-box domain is a protein structural motif of about 50 amino acids that mediates protein–protein interactions. The F-box protein is one of the four components of the SCF (SKp1, Cullin, F-box protein) complex, which mediates ubiquitination of proteins targeted for degradation by the proteasome, playing an essential role in many cellular processes. Several discoveries have been made on the use of the ubiquitin–proteasome system by viruses of several families to complete their infection cycle. On the other hand, F-box proteins can be used in the defense response by the host. This review describes the role of F-box proteins and the use of the ubiquitin–proteasome system in virus–host interactions. PMID:23429191

  15. IL-10: A Multifunctional Cytokine in Viral Infections

    PubMed Central

    2017-01-01

    The anti-inflammatory master regulator IL-10 is critical to protect the host from tissue damage during acute phases of immune responses. This regulatory mechanism, central to T cell homeostasis, can be hijacked by viruses to evade immunity. IL-10 can be produced by virtually all immune cells, and it can also modulate the function of these cells. Understanding the effects of this multifunctional cytokine is therefore a complex task. In the present review we discuss the factors driving IL-10 production and the cellular sources of the cytokine during antiviral immune responses. We particularly focus on the IL-10 regulatory mechanisms that impact antiviral immune responses and how viruses can use this central regulatory pathway to evade immunity and establish chronic/latent infections. PMID:28316998

  16. Tupaia Belangeri as an Experimental Animal Model for Viral Infection

    PubMed Central

    Tsukiyama-Kohara, Kyoko; Kohara, Michinori

    2014-01-01

    Tupaias, or tree shrews, are small mammals that are similar in appearance to squirrels. The morphological and behavioral characteristics of the group have been extensively characterized, and despite previously being classified as primates, recent studies have placed the group in its own family, the Tupaiidae. Genomic analysis has revealed that the genus Tupaia is closer to humans than it is to rodents. In addition, tupaias are susceptible to hepatitis B virus and hepatitis C virus. The only other experimental animal that has been demonstrated to be sensitive to both of these viruses is the chimpanzee, but restrictions on animal testing have meant that experiments using chimpanzees have become almost impossible. Consequently, the development of the tupaia for use as an animal infection model could become a powerful tool for hepatitis virus research and in preclinical studies on drug development. PMID:25048261

  17. Achalasia and viral infection: new insights from veterinary medicine.

    PubMed

    Ganem, Don; Kistler, Amy; DeRisi, Joseph

    2010-05-26

    Achalasia is a serious disorder in which the movement of food and liquids through the esophagus is impaired. It is currently thought to be caused by an inflammatory process that destroys neurons in myenteric ganglia, which affect peristalsis in the esophagus. The factor(s) that precipitate this inflammatory process are unknown; possibilities include environmental agents (such as microbes or toxins) and/or cell-mediated autoimmune reactivity. Recently, infection with a newly described bornavirus has been strongly linked to a disease of exotic birds that displays many striking similarities to achalasia. These findings demonstrate that viruses can induce achalasia-like pathophysiology and have renewed interest in the search for infectious agents in this enigmatic human disease.

  18. Tupaia belangeri as an experimental animal model for viral infection.

    PubMed

    Tsukiyama-Kohara, Kyoko; Kohara, Michinori

    2014-01-01

    Tupaias, or tree shrews, are small mammals that are similar in appearance to squirrels. The morphological and behavioral characteristics of the group have been extensively characterized, and despite previously being classified as primates, recent studies have placed the group in its own family, the Tupaiidae. Genomic analysis has revealed that the genus Tupaia is closer to humans than it is to rodents. In addition, tupaias are susceptible to hepatitis B virus and hepatitis C virus. The only other experimental animal that has been demonstrated to be sensitive to both of these viruses is the chimpanzee, but restrictions on animal testing have meant that experiments using chimpanzees have become almost impossible. Consequently, the development of the tupaia for use as an animal infection model could become a powerful tool for hepatitis virus research and in preclinical studies on drug development.

  19. IL-10: A Multifunctional Cytokine in Viral Infections.

    PubMed

    Rojas, José M; Avia, Miguel; Martín, Verónica; Sevilla, Noemí

    2017-01-01

    The anti-inflammatory master regulator IL-10 is critical to protect the host from tissue damage during acute phases of immune responses. This regulatory mechanism, central to T cell homeostasis, can be hijacked by viruses to evade immunity. IL-10 can be produced by virtually all immune cells, and it can also modulate the function of these cells. Understanding the effects of this multifunctional cytokine is therefore a complex task. In the present review we discuss the factors driving IL-10 production and the cellular sources of the cytokine during antiviral immune responses. We particularly focus on the IL-10 regulatory mechanisms that impact antiviral immune responses and how viruses can use this central regulatory pathway to evade immunity and establish chronic/latent infections.

  20. The use of sialidase therapy for respiratory viral infections.

    PubMed

    Nicholls, John M; Moss, Ronald B; Haslam, Stuart M

    2013-06-01

    DAS181 is an inhaled bacterial sialidase which functions by removing sialic acid (Sia) from the surface of epithelial cells, preventing attachment and subsequent infection by respiratory viruses that utilize Sia as a receptor. DAS181 is typical of bacterial sialidases in cleaving Sia α2-3 and Sia α2-6 linkages, and it also has a demonstrated effect against acetylated and hydroxylated forms of Sia. The potency of the compound has been enhanced by coupling the active sialidase with an amphiregulin tag, allowing a longer duration of action and minimizing spread to the systemic circulation. DAS181 is now in Phase II development for the treatment of influenza, and it has also demonstrated activity in individual cases of parainfluenza in immunosuppressed patients. Continued evaluation of the roles and activities of bacterial sialidases is required to expand the range of successful antiviral therapies targeting Sia or its derivatives.

  1. Neutralization of viral infectivity by zebrafish c-reactive protein isoforms.

    PubMed

    Bello-Perez, Melissa; Falco, Alberto; Medina-Gali, Regla; Pereiro, Patricia; Encinar, Jose Antonio; Novoa, Beatriz; Perez, Luis; Coll, Julio

    2017-09-12

    This work explores the unexpected in vivo and in vitro anti-viral functions of the seven c-reactive protein (crp1-7) genes of zebrafish (Danio rerio). First results showed heterogeneous crp1-7 transcript levels in healthy wild-type zebrafish tissues and organs and how those levels heterogeneously changed not only after bacterial but also after viral infections, including those in adaptive immunity-deficient rag1(-/-) mutants. As shown by microarray hybridization and proteomic techniques, crp2/CRP2 and crp5/CRP5 transcripts/proteins were among the most modulated during in vivo viral infection situations including the highest responses in the absence of adaptive immunity. In contrast crp1/CRP1/and crp7/CRP7 very often remained unmodulated. All evidences suggested that zebrafish crp2-6/CRP2-6 may have in vivo anti-viral activities in addition to their well known anti-bacterial and/or physiological functions in mammalians. Confirming those expectations, in vitro neutralization and in vivo protection against spring viremia carp virus (SVCV) infections were demonstrated by crp2-6/CRP2-6 using crp1-7 transfected and/or CRP1-7-enriched supernatant-treated fish cells and crp2-5-injected one-cell stage embryo eggs, respectively. All these findings discovered a crp1-7/CRP1-7 primitive anti-viral functional diversity.These findings may help to study similar functions on the one-gene-coded human CRP, which is widely used as a clinical biomarker for bacterial infections, tissue inflammation and coronary heart diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Contrasting Life Strategies of Viruses that Infect Photo- and Heterotrophic Bacteria, as Revealed by Viral Tagging

    PubMed Central

    Deng, Li; Gregory, Ann; Yilmaz, Suzan; Poulos, Bonnie T.; Hugenholtz, Philip; Sullivan, Matthew B.

    2012-01-01

    ABSTRACT Ocean viruses are ubiquitous and abundant and play important roles in global biogeochemical cycles by means of their mortality, horizontal gene transfer, and manipulation of host metabolism. However, the obstacles involved in linking viruses to their hosts in a high-throughput manner bottlenecks our ability to understand virus-host interactions in complex communities. We have developed a method called viral tagging (VT), which combines mixtures of host cells and fluorescent viruses with flow cytometry. We investigated multiple viruses which infect each of two model marine bacteria that represent the slow-growing, photoautotrophic genus Synechococcus (Cyanobacteria) and the fast-growing, heterotrophic genus Pseudoalteromonas (Gammaproteobacteria). Overall, viral tagging results for viral infection were consistent with plaque and liquid infection assays for cyanobacterial myo-, podo- and siphoviruses and some (myo- and podoviruses) but not all (four siphoviruses) heterotrophic bacterial viruses. Virus-tagged Pseudoalteromonas organisms were proportional to the added viruses under varied infection conditions (virus-bacterium ratios), while no more than 50% of the Synechococcus organisms were virus tagged even at viral abundances that exceeded (5 to 10×) that of their hosts. Further, we found that host growth phase minimally impacts the fraction of virus-tagged Synechococcus organisms while greatly affecting phage adsorption to Pseudoalteromonas. Together these findings suggest that at least two contrasting viral life strategies exist in the oceans and that they likely reflect adaptation to their host microbes. Looking forward to the point at which the virus-tagging signature is well understood (e.g., for Synechococcus), application to natural communities should begin to provide population genomic data at the proper scale for predictively modeling two of the most abundant biological entities on Earth. PMID:23111870

  3. Seasonality of viral respiratory infections in southeast of Brazil: the influence of temperature and air humidity

    PubMed Central

    Gardinassi, Luiz Gustavo; Marques Simas, Paulo Vitor; Salomão, João Batista; Durigon, Edison Luiz; Zanetta Trevisan, Dirce Maria; Cordeiro, José Antonio; Lacerda, Mauricio Nogueira; Rahal, Paula; de Souz, Fátima Pereira

    2012-01-01

    Viruses are the major cause of lower respiratory tract infections in childhood and the main viruses involved are Human Respiratory Syncytial Virus (HRSV), Human Metapneumovirus (HMPV), Influenzavirus A and B (FLUA and FLUB), Human Parainfluenza Virus 1, 2 and 3 (HPIV1, 2 and 3) and Human Rhinovirus (HRV). The purposes of this study were to detect respiratory viruses in hospitalized children younger than six years and identify the influence of temperature and relative air humidity on the detected viruses. Samples of nasopharyngeal washes were collected from hospitalized children between May/2004 and September/2005. Methods of viral detection were RT-PCR, PCR and HRV amplicons were confirmed by hybridization. Results showed 54% (148/272) of viral positivity. HRSV was detected in 29% (79/272) of the samples; HRV in 23.1% (63/272); HPIV3 in 5.1% (14/272); HMPV in 3.3% (9/272); HPIV1 in 2.9% (8/272); FLUB in 1.4% (4/272), FLUA in 1.1% (3/272), and HPIV2 in 0.3% (1/272). The highest detection rates occurred mainly in the spring 2004 and in the autumn 2005. It was observed that viral respiratory infections tend to increase as the relative air humidity decreases, showing significant association with monthly averages of minimal temperature and minimal relative air humidity. In conclusion, viral respiratory infections vary according to temperature and relative air humidity and viral respiratory infections present major incidences it coldest and driest periods. PMID:24031808

  4. A comparative review of HLA associations with hepatitis B and C viral infections across global populations.

    PubMed

    Singh, Rashmi; Kaul, Rashmi; Kaul, Anil; Khan, Khalid

    2007-03-28

    Hepatitis B (HBV) and hepatitis C (HCV) viral infection or co-infection leads to risk of development of chronic infection, cirrhosis and hepatocellular carcinoma (HCC). Immigration and globalization have added to the challenges of public health concerns regarding chronic HBV and HCV infections worldwide. The aim of this study is to review existing global literature across ethnic populations on HBV and HCV related human leukocyte antigen (HLA) associations in relation to susceptibility, viral persistence and treatment. Extensive literature search was conducted to explore the HLA associations in HBV and HCV infections reported across global populations over the past decade to understand the knowledge status, weaknesses and strengths of this information in different ethnic populations. HLA DR13 is consistently associated with HBV clearance globally. HLADRB1*11/*12 alleles and DQB1*0301 are associated with HBV persistence but with HCV clearance worldwide. Consistent association of DRB1*03 and *07 is observed with HCV susceptibility and non-responsiveness to HBV vaccination across the population. HLA DR13 is protective for vertical HBV and HCV transmission in Chinese and Italian neonates, but different alleles are associated with their susceptibility in these populations. HLA class I molecule interactions with Killer cell immunoglobulin like receptors (KIR) of natural killer (NK) cells modulate HCV infection outcome via regulating immune regulatory cells and molecules. HLA associations with HBV vaccination, interferon therapy in HBV and HCV, and with extra hepatic manifestations of viral hepatitis are also discussed. Systematic studies in compliance with global regulatory standards are required to identify the HLA specific viral epitope, stage specific T cell populations interacting with different HLA alleles during disease progression and viral clearance of chronic HBV or HCV infections among different ethnic populations. These studies would facilitate stage specific

  5. Diagnosing viral and bacterial respiratory infections in acute COPD exacerbations by an electronic nose: a pilot study.

    PubMed

    van Geffen, Wouter H; Bruins, Marcel; Kerstjens, Huib A M

    2016-06-16

    Respiratory infections, viral or bacterial, are a common cause of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). A rapid, point-of-care, and easy-to-use tool distinguishing viral and bacterial from other causes would be valuable in routine clinical care. An electronic nose (e-nose) could fit this profile but has never been tested in this setting before. In a single-center registered trial (NTR 4601) patients admitted with AECOPD were tested with the Aeonose(®) electronic nose, and a diagnosis of viral or bacterial infection was obtained by bacterial culture on sputa and viral PCR on nose swabs. A neural network with leave-10%-out cross-validation was used to assess the e-nose data. Forty three patients were included. In the bacterial infection model, 22 positive cases were tested versus the negatives; and similarly 18 positive cases were tested in the viral infection model. The Aeonose was able to distinguish between COPD-subjects suffering from a viral infection and COPD patients without infection, showing an area under the curve (AUC) of 0.74. Similarly, for bacterial infections, an AUC of 0.72 was obtained. The Aeonose e-nose yields promising results in 'smelling' the presence or absence of a viral or bacterial respiratory infection during an acute exacerbation of COPD. Validation of these results using a new and large cohort is required before introduction into clinical practice.

  6. Persistent fetal infection with bovine viral diarrhea virus differentially affects maternal blood cell signal transduction pathways.

    PubMed

    Smirnova, Natalia P; Ptitsyn, Andrey A; Austin, Kathleen J; Bielefeldt-Ohmann, Helle; Van Campen, Hana; Han, Hyungchul; van Olphen, Alberto L; Hansen, Thomas R

    2009-02-02

    The consequences of viral infection during pregnancy include impact on fetal and maternal immune responses and on fetal development. Transplacental infection in cattle with noncytopathic bovine viral diarrhea virus (ncpBVDV) during early gestation results in persistently infected (PI) fetuses with life-long viremia and susceptibility to infections. Infection of the fetus during the third trimester or after birth leads to a transient infection cleared by a competent immune system. We hypothesized that ncpBVDV infection and presence of an infected fetus would alter immune response and lead to downregulation of proinflammatory processes in pregnant dams. Naïve pregnant heifers were challenged with ncpBVDV2 on day 75 (PI fetus) and day 175 [transiently infected (TI) fetus] or kept uninfected (healthy control fetus). Maternal blood samples were collected up to day 190 of gestation. Genome-wide microarray analysis of gene expression in maternal peripheral white blood cells, performed on days 160 and 190 of gestation, revealed multiple signal transduction pathways affected by ncpBVDV infection. Acute infection and presence of a TI fetus caused upregulation of the type I interferon (IFN) pathway genes, including dsRNA sensors and IFN-stimulated genes. The presence of a PI fetus caused prolonged downregulation of chemokine receptor 4 (CXCR4) and T cell receptor (TCR) signaling in maternal blood cells. We conclude that: 1) infection with ncpBVDV induces a vigorous type I IFN response, and 2) presence of a PI fetus causes downregulation of important signaling pathways in the blood of the dam, which could have deleterious consequences on fetal development and the immune response.

  7. Recurrent and persistent respiratory tract viral infections in patients with primary hypogammaglobulinemia.

    PubMed

    Kainulainen, Leena; Vuorinen, Tytti; Rantakokko-Jalava, Kaisu; Osterback, Riikka; Ruuskanen, Olli

    2010-07-01

    The occurrence of respiratory tract viral infections in patients with primary hypogammaglobulinemia has not been studied. We conducted a prospective 12-month follow-up study of respiratory tract infections in 12 adult patients with primary hypogammaglobulinemia. Nasal swab samples and induced sputum samples were taken at the onset of acute respiratory tract infection and every 3 months thereafter. Samples were tested for bacteria and viruses. PCR tests were performed for 15 respiratory tract viruses. In case the results for rhinovirus were positive, follow-up nasal swab samples were taken every 2 weeks until rhinoviral PCR results became negative. Patients completed symptom diaries, which were collected every month. The spouses of the patients served as healthy control subjects. During the 12-month period, the 12 patients had 65 episodes of acute respiratory tract infections, and the 11 spouses had 12 acute episodes (P < .001). Respiratory tract viruses were found in sputum in 54% of the infections. Rhinovirus was the most common virus. In more than half of our patients, rhinoviral PCR results stayed positive for more than 2 months. The most long-acting persistence with the same rhinovirus was 4 months. Despite adequate immunoglobulin replacement therapy, patients with primary hypogammaglobulinemia have increased susceptibility to respiratory tract viral infections. Rhinoviral infections are frequent and prolonged. Copyright 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  8. Innate and adaptive immune responses to in utero infection with bovine viral diarrhea virus.

    PubMed

    Hansen, Thomas R; Smirnova, Natalia P; Webb, Brett T; Bielefeldt-Ohmann, Helle; Sacco, Randy E; Van Campen, Hana

    2015-06-01

    Infection of pregnant cows with noncytopathic (ncp) bovine viral diarrhea virus (BVDV) induces rapid innate and adaptive immune responses, resulting in clearance of the virus in less than 3 weeks. Seven to 14 days after inoculation of the cow, ncpBVDV crosses the placenta and induces a fetal viremia. Establishment of persistent infection with ncpBVDV in the fetus has been attributed to the inability to mount an immune response before 90-150 days of gestational age. The result is 'immune tolerance', persistent viral replication and shedding of ncpBVDV. In contrast, we describe the chronic upregulation of fetal Type I interferon (IFN) pathway genes and the induction of IFN-γ pathways in fetuses of cows infected on day 75 of gestation. Persistently infected (PI) fetal IFN-γ concentrations also increased at day 97 at the peak of fetal viremia and IFN-γ mRNA was significantly elevated in fetal thymus, liver and spleen 14-22 days post maternal inoculation. PI fetuses respond to ncpBVDV infection through induction of Type I IFN and IFN-γ activated genes leading to a reduction in ncpBVDV titer. We hypothesize that fetal infection with BVDV persists because of impaired induction of IFN-γ in the face of activated Type I IFN responses. Clarification of the mechanisms involved in the IFN-associated pathways during BVDV fetal infection may lead to better detection methods, antiviral compounds and selection of genetically resistant breeding animals.

  9. A retrospective study of viral central nervous system infections: relationship amongst aetiology, clinical course and outcome.

    PubMed

    Calleri, Guido; Libanore, Valentina; Corcione, Silvia; De Rosa, Francesco G; Caramello, Pietro

    2017-04-01

    To describe the clinical pattern of viral central nervous system (CNS) infections and compare meningitis and encephalitis. This is a retrospective study reporting the clinical characteristics and outcome of 138 cases of viral meningitis and meningoencephalitis in a real life experience at a referral centre in Turin, Northern Italy. Enteroviruses were predominant in younger patients who were mainly presenting with signs of meningitis, had shorter hospital admission and absence of complications, whereas herpesviruses had more often signs of encephalitis, were more frequent in elderly patients, had longer hospital admission and frequent complications and sequelae. Two main clinical entities with different epidemiology, clinical aspects and prognosis may be identified within the group of viral CNS inefctions.

  10. Modelling viral infections using zebrafish: Innate immune response and antiviral research.

    PubMed

    Varela, Mónica; Figueras, Antonio; Novoa, Beatriz

    2017-03-01

    Zebrafish possess a highly developed immune system that is remarkably similar to the human one. Therefore, it is expected that the majority of the signalling pathways and molecules involved in the immune response of mammals exist and behave similarly in fish. The innate antiviral response depends on the recognition of viral components by host cells. Pattern recognition receptors initiate antimicrobial defence mechanisms via several well-conserved signalling pathways. In this paper, we review current knowledge of the antiviral innate immune response in zebrafish by considering the main molecules that have been characterized and the infection models used for the in vivo study of the antiviral innate immune response. We next summarize published studies in which larval and adult zebrafish were used to study viral diseases of fish, then provide a similar review of studies of human viral diseases in zebrafish and experience with antiviral drug screening in this model organism. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Viral vector vaccines protect cockatiels from inflammatory lesions after heterologous parrot bornavirus 2 challenge infection.

    PubMed

    Runge, Solveig; Olbert, Marita; Herden, Christiane; Malberg, Sara; Römer-Oberdörfer, Angela; Staeheli, Peter; Rubbenstroth, Dennis

    2017-01-23

    Avian bornaviruses are causative agents of proventricular dilatation disease (PDD), a chronic neurologic and often fatal disorder of psittacines including endangered species. To date no causative therapy or immunoprophylaxis is available. Our previous work has shown that viral vector vaccines can delay the course of homologous bornavirus challenge infections but failed to protect against PDD when persistent infection was not prevented. The goal of this study was to refine our avian bornavirus vaccination and infection model to better represent natural bornavirus infections in order to achieve full protection against a heterologous challenge infection. We observed that parrot bornavirus 2 (PaBV-2) readily infected cockatiels (Nymphicus hollandicus) by combined intramuscular and subcutaneous injection with as little as 10(2.7)foci-forming units (ffu) per bird, whereas a 500-fold higher dose of the same virus administered via peroral and oculonasal route did not result in persistent infection. These results indicated that experimental bornavirus challenge infections with this virus should be performed via the parenteral route. Prime-boost vaccination of cockatiels with Newcastle disease virus (NDV) and modified vaccinia virus Ankara (MVA) vectors expressing the nucleoprotein and phosphoprotein genes of PaBV-4 substantially blocked bornavirus replication following parenteral challenge infection with 10(3.5)ffu of heterologous PaBV-2. Only two out of six vaccinated birds had very low viral levels detectable in a few organs. As a consequence, only one vaccinated bird developed mild PDD-associated microscopic lesions, while mock-vaccinated controls were not protected against PaBV-2 infection and inflammation. Our results demonstrate that NDV and MVA vector vaccines can protect against invasive heterologous bornavirus challenge infections and subsequent PDD. These vector vaccines represent a promising tool to combat avian bornaviruses in psittacine populations. Copyright

  12. Inhibition of Influenza A Virus Infection by Fucoidan Targeting Viral Neuraminidase and Cellular EGFR Pathway

    PubMed Central

    Wang, Wei; Wu, Jiandong; Zhang, Xiaoshuang; Hao, Cui; Zhao, Xiaoliang; Jiao, Guangling; Shan, Xindi; Tai, Wenjing; Yu, Guangli

    2017-01-01

    Development of novel anti-influenza A virus (IAV) drugs with high efficiency and low toxicity is critical for preparedness against influenza outbreaks. Herein, we investigated the anti-IAV activities and mechanisms of fucoidan in vitro and in vivo. The results showed that a fucoidan KW derived from brown algae Kjellmaniella crassifolia effectively blocked IAV infection in vitro with low toxicity. KW possessed broad anti-IAV spectrum and low tendency of induction of viral resistance, superior to the anti-IAV drug amantadine. KW was capable of inactivating virus particles before infection and blocked some stages after adsorption. KW could bind to viral neuraminidase (NA) and inhibit the activity of NA to block the release of IAV. KW also interfered with the activation of EGFR, PKCα, NF-κB, and Akt, and inhibited both IAV endocytosis and EGFR internalization in IAV-infected cells, suggesting that KW may also inhibit cellular EGFR pathway. Moreover, intranasal administration of KW markedly improved survival and decreased viral titers in IAV-infected mice. Therefore, fucoidan KW has the potential to be developed into a novel nasal drop or spray for prevention and treatment of influenza in the future. PMID:28094330

  13. Viral latency in blood and saliva of simian foamy virus-infected humans.

    PubMed

    Rua, Rejane; Betsem, Edouard; Gessain, Antoine

    2013-01-01

    Simian foamy viruses (SFV) are widespread retroviruses among non-human primates (NHP). SFV actively replicate in the oral cavity and can be transmitted to humans through NHP bites, giving rise to a persistent infection. We aimed at studying the natural history of SFV infection in human. We have analyzed viral load and gene expression in 14 hunters from Cameroon previously shown to be infected with a gorilla SFV strain. Viral DNA could be detected by quantitative polymerase chain reaction (q-PCR) targeting the pol-in region, in most samples of peripheral blood mononuclear cells (PBMCs) (7.1 ± 6.0 SFV DNA copies/105 PBMCs) and saliva (2.4 ± 4.3 SFV DNA copies/105 cells) derived from the hunters. However, quantitative real-time reverse-transcription polymerase chain reaction (RT)-qPCR revealed the absence of SFV viral gene expression in both PBMCs and saliva, suggesting that SFV was latent in the human samples. Our study demonstrates that a latent infection can occur in humans and persist for years, both in PBMCs and saliva. Such a scenario may contribute to the putative lack of secondary human-to-human transmissions of SFV.

  14. IL-21 is required for CD4 memory formation in response to viral infection

    PubMed Central

    Yuan, Yuqing; Huang, Xiaopei

    2017-01-01

    IL-21 has been shown to play an important role in the CD8 T cell response during acute and chronic viral infections. However, the role of IL-21 signaling in the CD4 T cell response to viral infection remains incompletely defined. In a model of infection with vaccinia virus, we show that intrinsic IL-21 signaling on CD4 T cells was critical for the formation of memory CD4 T cells in vivo. We further reveal that IL-21 promoted CD4 T cell survival in a mechanism dependent on activation of the STAT1 and STAT3 signaling pathways. In addition, the activation of Akt is also required for IL-21–dependent survival of CD4 T cells in vivo. These results identify a critical role for intrinsic IL-21 signaling in CD4 T cell survival and memory formation in response to viral infection in vivo and may provide insights into the design of effective vaccine strategies. PMID:28405614

  15. Identification of bovine viral diarrhea virus infection in Saanen goats in the Republic of Korea.

    PubMed

    Han, Yu-Jung; Chae, Jeong-Byoung; Chae, Joon-Seok; Yu, Do-Hyeon; Park, Jinho; Park, Bae-Keun; Kim, Hyeon-Cheol; Yoo, Jae-Gyu; Choi, Kyoung-Seong

    2016-06-01

    Bovine viral diarrhea virus (BVDV) is one of the most important viral pathogens of livestock and causes substantial economic losses to the livestock industry worldwide. BVDV is not necessarily species specific and is known to infect domesticated and wild ruminants. In the present study, BVDV infection was identified in two Saanen goats from one farm, and two different viral subtypes were found, BVDV-1a and BVDV-2a. Each isolate was closely related to cattle isolates identified in the Republic of Korea. The two sequences obtained in this study were not consistent with border disease virus (BDV). The incidence of BVDV in this farm apparently occurred in the absence of contact with cattle and may be associated with grazing. This study demonstrates that BVDV infection may be possible to transmit among goats without exposure to cattle. Therefore, this result indicates that Saanen goats may act as natural reservoirs for BVDV. This is the first report of BVDV-1a infection in a Saanen goat.

  16. Cross-dressed dendritic cells drive memory CD8+ T-cell activation after viral infection.

    PubMed

    Wakim, Linda M; Bevan, Michael J

    2011-03-31

    After an infection, cytotoxic T lymphocyte precursors proliferate and become effector cells by recognizing foreign peptides in the groove of major histocompatibility complex (MHC) class I molecules expressed by antigen-presenting cells (APCs). Professional APCs specialized for T-cell activation acquire viral antigen either by becoming infected themselves (direct presentation) or by phagocytosis of infected cells, followed by transfer of antigen to the cytosol, processing and MHC class I loading in a process referred to as cross-presentation. An alternative way, referred to as 'cross-dressing', by which an uninfected APC could present antigen was postulated to be by the transfer of preformed peptide-MHC complexes from the surface of an infected cell to the APC without the need of further processing. Here we show that this mechanism exists and boosts the antiviral response of mouse memory CD8(+) T cells. A number of publications have demonstrated sharing of peptide-loaded MHC molecules in vitro. Our in vitro experiments demonstrate that cross-dressing APCs do not acquire peptide-MHC complexes in the form of exosomes released by donor cells. Rather, the APCs and donor cells have to contact each other for the transfer to occur. After a viral infection, we could isolate cross-dressed APCs able to present viral antigen in vitro. Furthermore, using the diphtheria toxin system to selectively eliminate APCs that could only acquire viral peptide-MHC complexes by cross-dressing, we show that such presentation can promote the expansion of resting memory T cells. Notably, naive T cells were excluded from taking part in the response. Cross-dressing is a mechanism of antigen presentation used by dendritic cells that may have a significant role in activating previously primed CD8(+) T cells.

  17. Targeting Viral Entry for Treatment of Hepatitis B and C Virus Infections.

    PubMed

    Colpitts, Che C; Verrier, Eloi R; Baumert, Thomas F

    2015-09-11

    Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections remain major health problems worldwide, with 400-500 million chronically infected people worldwide. Chronic infection results in liver cirrhosis and hepatocellular carcinoma, the second leading cause of cancer death. Current treatments for HBV limit viral replication without efficiently curing infection. HCV treatment has markedly progressed with the licensing of direct-acting antivirals (DAAs) for HCV cure, yet limited access for the majority of patients is a major challenge. Preventative and curative treatment strategies, aimed at novel targets, are needed for both viruses. Viral entry represents one such target, although detailed knowledge of the entry mechanisms is a prerequisite. For HBV, the recent discovery of the NTCP cell entry factor enabled the establishment of an HBV cell culture model and showed that cyclosporin A and Myrcludex B are NTCP-targeting entry inhibitors. Advances in the understanding of HCV entry revealed it to be a complex process involving many factors, offering several antiviral targets. These include viral envelope proteins E1 and E2, virion-associated lipoprotein ApoE, and cellular factors CD81, SRBI, EGFR, claudin-1, occludin, and the cholesterol transporter NPC1L1. Small molecules targeting SR-BI, EGFR, and NPC1L1 have entered clinical trials, whereas other viral- and host-targeted small molecules, peptides, and antibodies show promise in preclinical models. This review summarizes the current understanding of HBV and HCV entry and describes novel antiviral targets and compounds in different stages of clinical development. Overall, proof-of-concept studies indicate that entry inhibitors are a promising class of antivirals to prevent and treat HBV and HCV infections.

  18. Zika plasma viral dynamics in nonhuman primates provides insights into early infection and antiviral strategies.

    PubMed

    Best, Katharine; Guedj, Jeremie; Madelain, Vincent; de Lamballerie, Xavier; Lim, So-Yon; Osuna, Christa E; Whitney, James B; Perelson, Alan S

    2017-08-15

    The recent outbreak of Zika virus (ZIKV) has been associated with fetal abnormalities and neurological complications, prompting global concern. Here we present a mathematical analysis of the within-host dynamics of plasma ZIKV burden in a nonhuman primate model, allowing for characterization of the growth and clearance of ZIKV within individual macaques. We estimate that the eclipse phase for ZIKV, the time between cell infection and viral production, is most likely short (∼4 h), the median within-host basic reproductive number R0 is 10.7, the rate of viral production is rapid (>25,000 virions d(-1)), and the lifetime of an infected cell while producing virus is ∼5 h. We also estimate that the minimum number of virions produced by an infected cell over its lifetime is ∼5,500. We assess the potential effect of an antiviral treatment that blocks viral replication, showing that the median time to undetectable plasma viral load (VL) can be reduced from ∼5 d to ∼3 d with a drug concentration ∼15 times the drug's EC50 when treatment is given prophylactically starting at the time of infection. In the case of favipiravir, a polymerase inhibitor with activity against ZIKV, we predict a dose of 150 mg/kg given twice a day initiated at the time of infection can reduce the peak median VL by ∼3 logs and shorten the time to undetectable median VL by ∼2 d, whereas treatment given 2 d postinfection is mostly ineffective in accelerating plasma VL loss in macaques.

  19. Comparison of type I and type II bovine viral diarrhea virus infection in swine.

    PubMed Central

    Walz, P H; Baker, J C; Mullaney, T P; Kaneene, J B; Maes, R K

    1999-01-01

    Some isolates of type II bovine viral diarrhea virus (BVDV) are capable of causing severe clinical disease in cattle. Bovine viral diarrhea virus infection has been reported in pigs, but the ability of these more virulent isolates of type II BVDV to induce severe clinical disease in pigs is unknown. It was our objective to compare clinical, virologic, and pathologic findings between type I and type II BVDV infection in pigs. Noninfected control and BVDV-infected 2-month-old pigs were used. A noncytopathic type I and a noncytopathic type II BVDV isolate were chosen for evaluation in feeder age swine based upon preliminary in vitro and in vivo experiments. A dose titration study was performed using 4 groups of 4 pigs for each viral isolate. The groups were inoculated intranasally with either sham (control), 10(3), 10(5), or 10(7) TCID50 of virus. The pigs were examined daily and clinical findings were recorded. Antemortem and postmortem samples were collected for virus isolation. Neither the type I nor type II BVDV isolates resulted in clinical signs of disease in pigs. Bovine viral diarrhea virus was isolated from antemortem and postmortem samples from groups of pigs receiving the 10(5) and the 10(7) TCID50 dose of the type I BVDV isolate. In contrast, BVDV was only isolated from postmortem samples in the group of pigs receiving the 10(7) TCID50 dose of the type II BVDV isolate. Type I BVDV was able to establish infection in pigs at lower doses by intranasal instillation than type II BVDV. Infection of pigs with a type II isolate of BVDV known to cause severe disease in calves did not result in clinically apparent disease in pigs. PMID:10369569

  20. Clinical Utility of Viral Load in Management of Cytomegalovirus Infection after Solid Organ Transplantation

    PubMed Central

    2013-01-01

    SUMMARY The negative impact of cytomegalovirus (CMV) infection on transplant outcomes warrants efforts toward improving its prevention, diagnosis, and treatment. During the last 2 decades, significant breakthroughs in diagnostic virology have facilitated remarkable improvements in CMV disease management. During this period, CMV nucleic acid amplification testing (NAT) evolved to become one of the most commonly performed tests in clinical virology laboratories. NAT provides a means for rapid and sensitive diagnosis of CMV infection in transplant recipients. Viral quantification also introduced several principles of CMV disease management. Specifically, viral load has been utilized (i) for prognostication of CMV disease, (ii) to guide preemptive therapy, (iii) to assess the efficacy of antiviral treatment, (iv) to guide the duration of treatment, and (v) to indicate the risk of clinical relapse or antiviral drug resistance. However, there remain important limitations that require further optimization, including the interassay variability in viral load reporting, which has limited the generation of standardized viral load thresholds for various clinical indications. The recent introduction of an international reference standard should advance the major goal of uniform viral load reporting and interpretation. However, it has also become apparent that other aspects of NAT should be standardized, including sample selection, nucleic acid extraction, amplification, detection, and calibration, among others. This review article synthesizes the vast amount of information on CMV NAT and provides a timely review of the clinical utility of viral load testing in the management of CMV in solid organ transplant recipients. Current limitations are highlighted, and avenues for further research are suggested to optimize the clinical application of NAT in the management of CMV after transplantation. PMID:24092851

  1. Optimizing Virus Identification in Critically Ill Children Suspected of Having an Acute Severe Viral Infection.

    PubMed

    Randolph, Adrienne G; Agan, Anna A; Flanagan, Ryan F; Meece, Jennifer K; Fitzgerald, Julie C; Loftis, Laura L; Truemper, Edward J; Li, Simon; Ferdinands, Jill M

    2016-04-01

    Multiplex rapid viral tests and nasopharyngeal flocked swabs are increasingly used for viral testing in PICUs. This study aimed at evaluating how the sampling site and the type of diagnostic test influence test results in children with suspected severe viral infection. Prospective cohort study. PICUs at 21 tertiary pediatric referral centers in the United States. During the 2010-2011 and 2011-2012 influenza seasons, we enrolled children (6 mo to 17 yr old) who were suspected to have severe viral infection. We collected samples by using a standardized protocol for nasopharyngeal aspirate and nasopharyngeal flocked swabs in nonintubated patients and for endotracheal tube aspirate and nasopharyngeal flocked swabs in intubated patients. Viral testing included a single reverse transcription-polymerase chain reaction influenza test and the GenMark Respiratory Viral Panel (20 viruses). We enrolled 90 endotracheally intubated and 133 nonintubated children. We identified influenza in 45 patients with reverse transcription-polymerase chain reaction testing; the multiplex panel was falsely negative for influenza in two patients (4.4%). Six patients (13.3%) had not been diagnosed with influenza in the PICU. Non-influenza viruses were identified in 172 of 223 children (77.1%). In nonintubated children, the same virus was identified by nasopharyngeal flocked swabs and nasopharyngeal aspirate in 133 of 183 paired samples (72.7%), with +nasopharyngeal aspirate/-nasopharyngeal flocked swabs in 32 of 183 paired samples (17.4%). In intubated children, the same virus was identified by nasopharyngeal flocked swabs and endotracheal tube aspirate in 67 of 94 paired samples (71.3%), with +nasopharyngeal flocked swabs/- endotracheal tube aspirate in 22 of 94 paired samples (23.4%). Most discrepancies were either adenovirus or rhinovirus in both groups. Standardized specimen collection and sensitive diagnostic testing with a reverse transcription-polymerase chain reaction increased the

  2. Restricted infectivity of ecotropic type C retroviruses in mouse teratocarcinoma cells: studies on viral DNA intermediates

    SciTech Connect

    Yang, W.K.; d'Auriol, L.; Yang, D.M.; Kiggans, J.O. Jr.; Ou, C.Y.; Peries, J.; Emanoil-Ravicovitch, R.

    1980-01-01

    Infectivity of retroviruses in cultured murine teratocarcinoma cells was found to be affected by the state of cellular differentiation. Present studies utilize two kinds of cell cultures from teratocarcinomas of mouse strain 129, an undifferentiated pluriopotential cell line (PCC/sub 4/) and a myoblast-derived cell line (PCD/sub 1/) which are respectively resistant and susceptible to the infection of Gross strain N-tropic type C retrovirus. Analyses of the appearance of free viral DNA intermediates in these cells from 4 to 78 h after virus inoculation were made. In both PCD/sub 1/ and PCC/sub 4/ cells, virus inoculation induced the formation of one linear form (III) and two covalently-closed supercoiled circular forms (I) of viral DNA duplexes; the linear form showing its appearance, increase, and decline in the 4 to 18 h period, and the circular forms in the 8 to 24 h period. In the period of 56 to 78 h after virus inoculation, a secondary burst of viral DNA synthesis occurred in PCD/sub 1/ cells, whereas both linear and supercoiled viral DNA duplexes became undetectable in PCC/sub 4/ cells. Free and unintegrated viral DNA preparations from PCD/sub 1/ and PCC/sub 4/ cells 10 h after virus inoculation were both infectious for N3T3 cells in a DNA transfection assay. Both PCD/sub 1/ and PCC/sub 4/ cells were very poor recipients for DNA transfection. These results indicate that restriction of retrovirus in undifferentiated teratocarcinoma cells occurs at a step beyond formation and maturation of viral DNA intermediates. (ERB)

  3. Novel microRNA-like viral small regulatory RNAs arising during human hepatitis A virus infection.

    PubMed

    Shi, Jiandong; Sun, Jing; Wang, Bin; Wu, Meini; Zhang, Jing; Duan, Zhiqing; Wang, Haixuan; Hu, Ningzhu; Hu, Yunzhang

    2014-10-01

    MicroRNAs (miRNAs), including host miRNAs and viral miRNAs, play vital roles in regulating host-virus interactions. DNA viruses encode miRNAs that regulate the viral life cycle. However, it is generally believed that cytoplasmic RNA viruses do not encode miRNAs, owing to inaccessible cellular miRNA processing machinery. Here, we provide a comprehensive genome-wide analysis and identification of miRNAs that were derived from hepatitis A virus (HAV; Hu/China/H2/1982), which is a typical cytoplasmic RNA virus. Using deep-sequencing and in silico approaches, we identified 2 novel virally encoded miRNAs, named hav-miR-1-5p and hav-miR-2-5p. Both of the novel virally encoded miRNAs were clearly detected in infected cells. Analysis of Dicer enzyme silencing demonstrated that HAV-derived miRNA biogenesis is Dicer dependent. Furthermore, we confirmed that HAV mature miRNAs were generated from viral miRNA precursors (pre-miRNAs) in host cells. Notably, naturally derived HAV miRNAs were biologically and functionally active and induced post-transcriptional gene silencing (PTGS). Genomic location analysis revealed novel miRNAs located in the coding region of the viral genome. Overall, our results show that HAV naturally generates functional miRNA-like small regulatory RNAs during infection. This is the first report of miRNAs derived from the coding region of genomic RNA of a cytoplasmic RNA virus. These observations demonstrate that a cytoplasmic RNA virus can naturally generate functional miRNAs, as DNA viruses do. These findings also contribute to improved understanding of host-RNA virus interactions mediated by RNA virus-derived miRNAs.

  4. Viral infections stimulate the metabolism and shape prokaryotic assemblages in submarine mud volcanoes

    PubMed Central

    Corinaldesi, Cinzia; Dell'Anno, Antonio; Danovaro, Roberto

    2012-01-01

    Mud volcanoes are geological structures in the oceans that have key roles in the functioning of the global ecosystem. Information on the dynamics of benthic viruses and their interactions with prokaryotes in mud volcano ecosystems is still completely lacking. We investigated the impact of viral infection on the mortality and assemblage structure of benthic prokaryotes of five mud volcanoes in the Mediterranean Sea. Mud volcano sediments promote high rates of viral production (1.65–7.89 × 109 viruses g−1 d−1), viral-induced prokaryotic mortality (VIPM) (33% cells killed per day) and heterotrophic prokaryotic production (3.0–8.3 μgC g−1 d−1) when compared with sediments outside the mud volcano area. The viral shunt (that is, the microbial biomass converted into dissolved organic matter as a result of viral infection, and thus diverted away from higher trophic levels) provides 49 mgC m−2 d−1, thus fuelling the metabolism of uninfected prokaryotes and contributing to the total C budget. Bacteria are the dominant components of prokaryotic assemblages in surface sediments of mud volcanoes, whereas archaea dominate the subsurface sediment layers. Multivariate multiple regression analyses show that prokaryotic assemblage composition is not only dependant on the geochemical features and processes of mud volcano ecosystems but also on synergistic interactions between bottom-up (that is, trophic resources) and top-down (that is, VIPM) controlling factors. Overall, these findings highlight the significant role of the viral shunt in sustaining the metabolism of prokaryotes and shaping their assemblage structure in mud volcano sediments, and they provide new clues for our understanding of the functioning of cold-seep ecosystems. PMID:22170423

  5. Viral infections stimulate the metabolism and shape prokaryotic assemblages in submarine mud volcanoes.

    PubMed

    Corinaldesi, Cinzia; Dell'Anno, Antonio; Danovaro, Roberto

    2012-06-01

    Mud volcanoes are geological structures in the oceans that have key roles in the functioning of the global ecosystem. Information on the dynamics of benthic viruses and their interactions with prokaryotes in mud volcano ecosystems is still completely lacking. We investigated the impact of viral infection on the mortality and assemblage structure of benthic prokaryotes of five mud volcanoes in the Mediterranean Sea. Mud volcano sediments promote high rates of viral production (1.65-7.89 × 10(9) viruses g(-1) d(-1)), viral-induced prokaryotic mortality (VIPM) (33% cells killed per day) and heterotrophic prokaryotic production (3.0-8.3 μgC g(-1) d(-1)) when compared with sediments outside the mud volcano area. The viral shunt (that is, the microbial biomass converted into dissolved organic matter as a result of viral infection, and thus diverted away from higher trophic levels) provides 49 mgC m(-2) d(-1), thus fuelling the metabolism of uninfected prokaryotes and contributing to the total C budget. Bacteria are the dominant components of prokaryotic assemblages in surface sediments of mud volcanoes, whereas archaea dominate the subsurface sediment layers. Multivariate multiple regression analyses show that prokaryotic assemblage composition is not only dependant on the geochemical features and processes of mud volcano ecosystems but also on synergistic interactions between bottom-up (that is, trophic resources) and top-down (that is, VIPM) controlling factors. Overall, these findings highlight the significant role of the viral shunt in sustaining the metabolism of prokaryotes and shaping their assemblage structure in mud volcano sediments, and they provide new clues for our understanding of the functioning of cold-seep ecosystems.

  6. Parallel epigenomic and transcriptomic responses to viral infection in honey bees (Apis mellifera).

    PubMed

    Galbraith, David A; Yang, Xingyu; Niño, Elina Lastro; Yi, Soojin; Grozinger, Christina

    2015-03-01

    Populations of honey bees are declining throughout the world, with US beekeepers losing 30% of their colonies each winter. Though multiple factors are driving these colony losses, it is increasingly clear that viruses play a major role. However, information about the molecular mechanisms mediating antiviral immunity in honey bees is surprisingly limited. Here, we examined the transcriptional and epigenetic (DNA methylation) responses to viral infection in honey bee workers. One-day old worker honey bees were fed solutions containing Israeli Acute Paralysis Virus (IAPV), a virus which causes muscle paralysis and death and has previously been associated with colony loss. Uninfected control and infected, symptomatic bees were collected within 20-24 hours after infection. Worker fat bodies, the primary tissue involved in metabolism, detoxification and immune responses, were collected for analysis. We performed transcriptome- and bisulfite-sequencing of the worker fat bodies to identify genome-wide gene expression and DNA methylation patterns associated with viral infection. There were 753 differentially expressed genes (FDR<0.05) in infected versus control bees, including several genes involved in epigenetic and antiviral pathways. DNA methylation status of 156 genes (FDR<0.1) changed significantly as a result of the infection, including those involved in antiviral responses in humans. There was no significant overlap between the significantly differentially expressed and significantly differentially methylated genes, and indeed, the genomic characteristics of these sets of genes were quite distinct. Our results indicate that honey bees have two distinct molecular pathways, mediated by transcription and methylation, that modulate protein levels and/or function in response to viral infections.

  7. Identification of viral infections in the prostate and evaluation of their association with cancer

    PubMed Central

    2010-01-01

    Background Several viruses with known oncogenic potential infect prostate tissue, among these are the polyomaviruses BKV, JCV, and SV40; human papillomaviruses (HPVs), and human cytomegalovirus (HCMV) infections. Recently, the Xenotropic Murine Leukemia Virus-related gammaretrovirus (XMRV) was identified in prostate tissue with a high prevalence observed in prostate cancer (PC) patients homozygous for the glutamine variant of the RNASEL protein (462Q/Q). Association studies with the R462Q allele and non-XMRV viruses have not been reported. We assessed associations between prostate cancer, prostate viral infections, and the RNASEL 462Q allele in Mexican cancer patients and controls. Methods 130 subjects (55 prostate cancer cases and 75 controls) were enrolled in the study. DNA and RNA isolated from prostate tissues were screened for the presence of viral genomes. Genotyping of the RNASEL R462Q variant was performed by Taqman method. Results R/R, R/Q, and Q/Q frequencies for R462Q were 0.62, 0.38, and 0.0 for PC cases and 0.69, 0.24, and 0.07 for controls, respectively. HPV sequences were detected in 11 (20.0%) cases and 4 (5.3%) controls. XMRV and HCMV infections were detected in one and six control samples, respectively. The risk of PC was significantly increased (Odds Ratio = 3.98; 95% CI: 1.17-13.56, p = 0.027) by infection of the prostatic tissue with HPV. BKV, JCV, and SV40 sequences were not detected in any of the tissue samples examined. Conclusions We report a positive association between PC and HPV infection. The 462Q/Q RNASEL genotype was not represented in our PC cases; thus, its interaction with prostate viral infections and cancer could not be evaluated. PMID:20576103

  8. CD200 receptor controls sex-specific TLR7 responses to viral infection.

    PubMed

    Karnam, Guruswamy; Rygiel, Tomasz P; Raaben, Matthijs; Grinwis, Guy C M; Coenjaerts, Frank E; Ressing, Maaike E; Rottier, Peter J M; de Haan, Cornelis A M; Meyaard, Linde

    2012-01-01

    Immunological checkpoints, such as the inhibitory CD200 receptor (CD200R), play a dual role in balancing the immune system during microbial infection. On the one hand these inhibitory signals prevent excessive immune mediated pathology but on the other hand they may impair clearance of the pathogen. We studied the influence of the inhibitory CD200-CD200R axis on clearance and pathology in two different virus infection models. We find that lack of CD200R signaling strongly enhances type I interferon (IFN) production and viral clearance and improves the outcome of mouse hepatitis corona virus (MHV) infection, particularly in female mice. MHV clearance is known to be dependent on Toll like receptor 7 (TLR7)-mediated type I IFN production and sex differences in TLR7 responses previously have been reported for humans. We therefore hypothesize that CD200R ligation suppresses TLR7 responses and that release of this inhibition enlarges sex differences in TLR7 signaling. This hypothesis is supported by our findings that in vivo administration of synthetic TLR7 ligand leads to enhanced type I IFN production, particularly in female Cd200(-/-) mice and that CD200R ligation inhibits TLR7 signaling in vitro. In influenza A virus infection we show that viral clearance is determined by sex but not by CD200R signaling. However, absence of CD200R in influenza A virus infection results in enhanced lung neutrophil influx and pathology in females. Thus, CD200-CD200R and sex are host factors that together determine the outcome of viral infection. Our data predict a sex bias in both beneficial and pathological immune responses to virus infection upon therapeutic targeting of CD200-CD200R.

  9. Parallel Epigenomic and Transcriptomic Responses to Viral Infection in Honey Bees (Apis mellifera)

    PubMed Central

    Niño, Elina Lastro; Yi, Soojin; Grozinger, Christina

    2015-01-01

    Populations of honey bees are declining throughout the world, with US beekeepers losing 30% of their colonies each winter. Though multiple factors are driving these colony losses, it is increasingly clear that viruses play a major role. However, information about the molecular mechanisms mediating antiviral immunity in honey bees is surprisingly limited. Here, we examined the transcriptional and epigenetic (DNA methylation) responses to viral infection in honey bee workers. One-day old worker honey bees were fed solutions containing Israeli Acute Paralysis Virus (IAPV), a virus which causes muscle paralysis and death and has previously been associated with colony loss. Uninfected control and infected, symptomatic bees were collected within 20–24 hours after infection. Worker fat bodies, the primary tissue involved in metabolism, detoxification and immune responses, were collected for analysis. We performed transcriptome- and bisulfite-sequencing of the worker fat bodies to identify genome-wide gene expression and DNA methylation patterns associated with viral infection. There were 753 differentially expressed genes (FDR<0.05) in infected versus control bees, including several genes involved in epigenetic and antiviral pathways. DNA methylation status of 156 genes (FDR<0.1) changed significantly as a result of the infection, including those involved in antiviral responses in humans. There was no significant overlap between the significantly differentially expressed and significantly differentially methylated genes, and indeed, the genomic characteristics of these sets of genes were quite distinct. Our results indicate that honey bees have two distinct molecular pathways, mediated by transcription and methylation, that modulate protein levels and/or function in response to viral infections. PMID:25811620

  10. [Laboratory diagnosis of HIV infection, viral tropism and resistance to antiretrovirals].

    PubMed

    García, Federico; Álvarez, Marta; Bernal, Carmen; Chueca, Natalia; Guillot, Vicente

    2011-04-01

    The accurate diagnosis of HIV infection demands that to consider a positive result, at least three assays with different antigenic base should be used, one of them, Western-Blot being mandatory for confirmation. Fourth generation ELISAs shorten the window phase to 13-15 days, as they now include p24 antigen detection. Proviral DNA or Viral RNA detection by molecular methods have proved useful for addressing complex situations in which serology was inconclusive. Viral load (HIV-RNA) is routinely used to follow-up HIV infected patients and is used for treatment initiation decisions. It is also used to monitor viral failure. When this happens, resistance tests are needed to guide treatment changes. Resistance is also used to assess the transmission of drug resistance to newly diagnosed patients. Finally, before using an anti-CCR5 drug, viral tropism needs to be determined. This can be done using genotypic tests, widely available in many HIV labs, or phenotypic tests, only available at certain sites. Copyright © 2010 Elsevier España, S.L. All rights reserved.

  11. Carbohydrate-Based Ice Recrystallization Inhibitors Increase Infectivity and Thermostability of Viral Vectors

    NASA Astrophysics Data System (ADS)

    Ghobadloo, Shahrokh M.; Balcerzak, Anna K.; Gargaun, Ana; Muharemagic, Darija; Mironov, Gleb G.; Capicciotti, Chantelle J.; Briard, Jennie G.; Ben, Robert N.; Berezovski, Maxim V.

    2014-07-01

    The inability of vaccines to retain sufficient thermostability has been an obstacle to global vaccination programs. To address this major limitation, we utilized carbohydrate-based ice recrystallization inhibitors (IRIs) to eliminate the cold chain and stabilize the potency of Vaccinia virus (VV), Vesicular Stomatitis virus (VSV) and Herpes virus-1 (HSV-1). The impact of these IRIs was tested on the potency of the viral vectors using a plaque forming unit assay following room temperature storage, cryopreservation with successive freeze-thaw cycles and lyophilization. Viral potency after storage with all three conditions demonstrated that N-octyl-gluconamide (NOGlc) recovered the infectivity of shelf stored VV, 5.6 Log10 PFU mL-1 during 40 days, and HSV-1, 2.7 Log10 PFU mL-1 during 9 days. Carbon-linked antifreeze glycoprotein analogue ornithine-glycine-glycine-galactose (OGG-Gal) increases the recovery of VV and VSV more than 1 Log10 PFU mL-1 after 10 freeze-thaw cycles. In VSV, cryostorage with OGG-Gal maintains high infectivity and reduces temperature-induced aggregation of viral particles by 2 times that of the control. In total, OGG-Gal and NOGlc preserve virus potency during cryostorage. Remarkably, NOGlc has potential to eliminate the cold chain and permit room temperature storage of viral vectors.

  12. US28, a Virally-Encoded GPCR as an Antiviral Target for Human Cytomegalovirus Infection

    PubMed Central

    Lee, Sungjin; Chung, Yoon Hee; Lee, Choongho

    2017-01-01

    Viruses continue to evolve a new strategy to take advantage of every aspect of host cells in order to maximize their survival. Due to their central roles in transducing a variety of transmembrane signals, GPCRs seem to be a prime target for viruses to pirate for their own use. Incorporation of GPCR functionality into the genome of herpesviruses has been demonstrated to be essential for pathogenesis of many herpesviruses-induced diseases. Here, we introduce US28 of human cytomegalovirus (HCMV) as the best-studied example of virally-encoded GPCRs to manipulate host GPCR signaling. In this review, we wish to summarize a number of US28-related topics including its regulation of host signaling pathways, its constitutive internalization, its structural and functional analysis, its roles in HCMV biology and pathogenesis, its proliferative activities and role in oncogenesis, and pharmacological modulation of its biological activities. This review will aid in our understanding of how pathogenic viruses usurp the host GPCR signaling for successful viral infection. This kind of knowledge will enable us to build a better strategy to control viral infection by normalizing the virally-dysregulated host GPCR signaling. PMID:28035083

  13. Brain heterogeneity leads to differential innate immune responses and modulates pathogenesis of viral infections.

    PubMed

    Zegenhagen, Loreen; Kurhade, Chaitanya; Koniszewski, Nikolaus; Överby, Anna K; Kröger, Andrea

    2016-08-01

    The central nervous system (CNS) is a highly complex organ with highly specialized cell subtypes. Viral infections often target specific structures of the brain and replicate in certain regions. Studies in mice deficient in type I Interferon (IFN) receptor or IFN-β have highlighted the importance of the type I IFN system against viral infections and non-viral autoimmune disorders in the CNS. Direct antiviral effects of type I IFNs appear to be crucial in limiting early spread of a number of viruses in CNS tissues. Increased efforts have been made to characterize IFN expression and responses in the brain. In this context, it is important to identify cells that produce IFN, decipher pathways leading to type I IFN expression and to characterize responding cells. In this review we give an overview about region specific aspects that influence local innate immune responses. The route of entry is critical, but also the susceptibility of different cell types, heterogeneity in subpopulations and micro-environmental cues play an important role in antiviral responses. Recent work has outlined the tremendous importance of type I IFNs, particularly in the limitation of viral spread within the CNS. This review will address recent advances in understanding the mechanisms of local type I IFN production and response, in the particular context of the CNS. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Robust classification of bacterial and viral infections via integrated host gene expression diagnostics

    PubMed Central

    Sweeney, Timothy E.; Wong, Hector R.; Khatri, Purvesh

    2017-01-01

    Improved diagnostics for acute infections could decrease morbidity and mortality by increasing early antibiotics for patients with bacterial infections and reducing unnecessary antibiotics for patients without bacterial infections. Several groups have used gene expression microarrays to build classifiers for acute infections, but these have been hampered by the size of the gene sets, use of overfit models, or lack of independent validation. We used multicohort analysis to derive a set of seven genes for robust discrimination of bacterial and viral infections, which we then validated in 30 independent cohorts. We next used our previously published 11-gene Sepsis MetaScore together with the new bacterial/viral classifier to build an integrated antibiotics decision model. In a pooled analysis of 1057 samples from 20 cohorts (excluding infants), the integrated antibiotics decision model had a sensitivity and specificity for bacterial infections of 94.0 and 59.8%, respectively (negative likelihood ratio, 0.10). Prospective clinical validation will be needed before these findings are implemented for patient care. PMID:27384347

  15. Transmission of viral infections by the water route: implications for developing countries.

    PubMed

    Ramia, S

    1985-01-01

    The "enteric" virus group comprises greater than 100 different viruses. These viruses typically infect the cell lining of the alimentary canal and are discharged in very large numbers in the feces of infected persons. Contamination of water supplies by enteric viruses represents an important source of viral infection. Many communities, particularly in developing countries, depend on sewage-polluted sources for their recreational and drinking water. Because conventional methods of sewage and water treatment have proved inefficient in the removal and inactivation of most enteric viruses, great concern has been raised over the impact of waterborne infection on the health of such communities. Current evidence implicating drinking and recreational water supplies in the transmission of nonbacterial gastroenteritis and hepatitis A virus and adenovirus infections is overwhelming. Water-borne transmission of other enteric viruses is also possible. Effective antiviral drugs are generally unavailable, and current vaccines can control only a limited number of viral infections; therefore, provision of uncontaminated water is a basic requirement in raising the standard of health in affected communities.

  16. Gene expression analysis during acute hepatitis C virus infection associates dendritic cell activation with viral clearance.

    PubMed

    Zabaleta, Aintzane; Riezu-Boj, Jose-Ignacio; Larrea, Esther; Villanueva, Lorea; Lasarte, Juan Jose; Guruceaga, Elizabeth; Fisicaro, Paola; Ezzikouri, Sayeh; Missale, Gabriele; Ferrari, Carlo; Benjelloun, Soumaya; Prieto, Jesús; Sarobe, Pablo

    2016-05-01

    Viral clearance during acute hepatitis C virus (HCV) infection is associated with the induction of potent antiviral T-cell responses. Since dendritic cells (DC) are essential in the activation of primary T-cell responses, gene expression was analyzed in DC from patients during acute HCV infection. By using microarrays, gene expression was compared in resting and activated peripheral blood plasmacytoid (pDC) and myeloid (mDC) DC from acute HCV resolving patients (AR) and from patients who become chronically infected (ANR), as well as in healthy individuals (CTRL) and chronically-infected patients (CHR). For pDC, a high number of upregulated genes was found in AR patients, irrespective of DC stimulation. However, for mDC, most evident differences were detected after DC stimulation, again corresponding to upregulated genes in AR patients. Divergent behavior of ANR was also observed when analyzing DC from CTRL and CHR, with ANR patients clustering again apart from these groups. These differences corresponded to metabolism-associated genes and genes belonging to pathways relevant for DC activation and cytokine responses. Thus, upregulation of relevant genes in DC during acute HCV infection may determine viral clearance, suggesting that dysfunctional DC may be responsible for the lack of efficient T-cell responses which lead to chronic HCV infection.

  17. The role of viral infection in inducing variability in virus-free progeny in tomato.

    PubMed

    Marii, Liliana; Chiriac, Gheorghe

    2009-05-01

    The effect of virus-host interactions on subsequent generations is poorly understood. The evaluation of the effects of viral infection on inheritance of quantitative traits in the progeny of infected plants and elucidation of a possible relationship between chiasma frequency in the infected plants and variability of traits in the progeny were investigated. The current study involved genotypes of four intraspecific hybrids of tomato (Solanum lycopersicum L.), their parental forms and two additional cultivars. Used as infection were the tobacco mosaic virus (TMV) and potato virus X (PVX). The consequences of the effect of viral infection were evaluated based on chromosome pairing in diakinesis and/or by examining quantitative and qualitative traits in the progeny of the infected tomato plants. Tomato plants infected with TMV + PVX were found to differ in chiasma frequency per pollen mother cell or per bivalent. Deviations have been observed for genotypes of both F(1) hybrids and cultivars. At the same time, differences in mean values of the traits under study have only been found for progeny populations (F(2)-F(4)) derived from virus-infected F(1) hybrids, but not in the case of progeny of the infected cultivars. The rate of recombinants combining traits of both parents increased significantly (2.22-8.24 times) in progeny populations of hybrids infected with TMV + PVX. The above suggests that the observed effects could be the result of modification of recombination frequencies that can be manifested in heterozygous hybrids and make small contributions to variability in cases of 'homozygous' tomato genotypes (i.e. cultivars).

  18. A Novel Host-Proteome Signature for Distinguishing between Acute Bacterial and Viral Infections

    PubMed Central

    Oved, Kfir; Cohen, Asi; Boico, Olga; Navon, Roy; Friedman, Tom; Etshtein, Liat; Kriger, Or; Bamberger, Ellen; Fonar, Yura; Yacobov, Renata; Wolchinsky, Ron; Denkberg, Galit; Dotan, Yaniv; Hochberg, Amit; Reiter, Yoram; Grupper, Moti; Srugo, Isaac; Feigin, Paul; Gorfine, Malka; Chistyakov, Irina; Dagan, Ron; Klein, Adi; Potasman, Israel; Eden, Eran

    2015-01-01

    Bacterial and viral infections are often clinically indistinguishable, leading to inappropriate patient management and antibiotic misuse. Bacterial-induced host proteins such as procalcitonin, C-reactive protein (CRP), and Interleukin-6, are routinely used to support diagnosis of infection. However, their performance is negatively affected by inter-patient variability, including time from symptom onset, clinical syndrome, and pathogens. Our aim was to identify novel viral-induced host proteins that can complement bacterial-induced proteins to increase diagnostic accuracy. Initially, we conducted a bioinformatic screen to identify putative circulating host immune response proteins. The resulting 600 candidates were then quantitatively screened for diagnostic potential using blood samples from 1002 prospectively recruited patients with suspected acute infectious disease and controls with no apparent infection. For each patient, three independent physicians assigned a diagnosis based on comprehensive clinical and laboratory investigation including PCR for 21 pathogens yielding 319 bacterial, 334 viral, 112 control and 98 indeterminate diagnoses; 139 patients were excluded based on predetermined criteria. The best performing host-protein was TNF-related apoptosis-inducing ligand (TRAIL) (area under the curve [AUC] of 0.89; 95% confidence in