Molecular biology and genetic diversity of Rift Valley fever virus.

PubMed

Ikegami, Tetsuro

2012-09-01

Rift Valley fever virus (RVFV), a member of the family Bunyaviridae, genus Phlebovirus, is the causative agent of Rift Valley fever (RVF), a mosquito-borne disease of ruminant animals and humans. The generation of a large sequence database has facilitated studies of the evolution and spread of the virus. Bayesian analyses indicate that currently circulating strains of RVFV are descended from an ancestral species that emerged from a natural reservoir in Africa when large-scale cattle and sheep farming were introduced during the 19th century. Viruses descended from multiple lineages persist in that region, through infection of reservoir animals and vertical transmission in mosquitoes, emerging in years of heavy rainfall to cause epizootics and epidemics. On a number of occasions, viruses from these lineages have been transported outside the enzootic region through the movement of infected animals or mosquitoes, triggering outbreaks in countries such as Egypt, Saudi Arabia, Mauritania and Madagascar, where RVF had not previously been seen. Such viruses could potentially become established in their new environments through infection of wild and domestic ruminants and other animals and vertical transmission in local mosquito species. Despite their extensive geographic dispersion, all strains of RVFV remain closely related at the nucleotide and amino acid level. The high degree of conservation of genes encoding the virion surface glycoproteins suggests that a single vaccine should protect against all currently circulating RVFV strains. Similarly, preservation of the sequence of the RNA-dependent RNA polymerase across viral lineages implies that antiviral drugs targeting the enzyme should be effective against all strains. Researchers should be encouraged to collect additional RVFV isolates and perform whole-genome sequencing and phylogenetic analysis, so as to enhance our understanding of the continuing evolution of this important virus. This review forms part of a series

Studies of Infection and Dissemination of Rift Valley Fever Virus in Mosquitoes.

DTIC Science & Technology

1991-10-15

have carried out the following studies:(l) Ultrastructural study of Rift Valley fever ( RVF ) virions in the cardia. (2) Immunocytochemical studies of...tissues for RVF virus in hemocoelically-infected Cx. pipiens. (5) Development of an immunogold procedure for in situ labelling of RVF viri-ons in electron...microscopic preps. (6) Worked toward the idetiTifTcation and isolation of the mosquito cell surface receptor molecule for RVF virus. (7) Developed and

Studies of Infection and Dissemination of Rift Valley Fever Virus in Mosquitoes

DTIC Science & Technology

1990-05-01

study of Rift Valley fever ( RVF ) virus in mosquitoes. During this year, we~havelcarrled out: (1) Immuno- cytochemical and ultrastructurai studies of...the proventriculus of adult, fkmale CuIex o infected with RVF virus. (2) irlmunocytochomical studies of the salivary glands and other tissues in...3) work on the development of an Immunogold procedure for InL.si labelling of RVF virlons In -_ + 20. DISTRIBUTION /AVAILABILITY OF ABSTRACT 21

Potential for North American Mosquitoes to Transmit Rift Valley Fever Virus

USDA-ARS?s Scientific Manuscript database

The recent outbreaks of disease caused by Rift Valley fever virus (RVFV) in Kenya, Mauritania, Yemen, Tanzania, Somalia, and Madagascar indicate the potential for RVFV to cause severe disease in both humans and domestic animals and its potential to be introduced into new areas, including North Ameri...

A Fusion-Inhibiting Peptide against Rift Valley Fever Virus Inhibits Multiple, Diverse Viruses

PubMed Central

Koehler, Jeffrey W.; Smith, Jeffrey M.; Ripoll, Daniel R.; Spik, Kristin W.; Taylor, Shannon L.; Badger, Catherine V.; Grant, Rebecca J.; Ogg, Monica M.; Wallqvist, Anders; Guttieri, Mary C.; Garry, Robert F.; Schmaljohn, Connie S.

2013-01-01

For enveloped viruses, fusion of the viral envelope with a cellular membrane is critical for a productive infection to occur. This fusion process is mediated by at least three classes of fusion proteins (Class I, II, and III) based on the protein sequence and structure. For Rift Valley fever virus (RVFV), the glycoprotein Gc (Class II fusion protein) mediates this fusion event following entry into the endocytic pathway, allowing the viral genome access to the cell cytoplasm. Here, we show that peptides analogous to the RVFV Gc stem region inhibited RVFV infectivity in cell culture by inhibiting the fusion process. Further, we show that infectivity can be inhibited for diverse, unrelated RNA viruses that have Class I (Ebola virus), Class II (Andes virus), or Class III (vesicular stomatitis virus) fusion proteins using this single peptide. Our findings are consistent with an inhibition mechanism similar to that proposed for stem peptide fusion inhibitors of dengue virus in which the RVFV inhibitory peptide first binds to both the virion and cell membranes, allowing it to traffic with the virus into the endocytic pathway. Upon acidification and rearrangement of Gc, the peptide is then able to specifically bind to Gc and prevent fusion of the viral and endocytic membranes, thus inhibiting viral infection. These results could provide novel insights into conserved features among the three classes of viral fusion proteins and offer direction for the future development of broadly active fusion inhibitors. PMID:24069485

Pathogenicity testing of influenza candidate vaccine viruses in the ferret model.

PubMed

Belser, Jessica A; Johnson, Adam; Pulit-Penaloza, Joanna A; Pappas, Claudia; Pearce, Melissa B; Tzeng, Wen-Pin; Hossain, M Jaber; Ridenour, Callie; Wang, Li; Chen, Li-Mei; Wentworth, David E; Katz, Jacqueline M; Maines, Taronna R; Tumpey, Terrence M

2017-11-01

The development of influenza candidate vaccine viruses (CVVs) for pre-pandemic vaccine production represents a critical step in pandemic preparedness. The multiple subtypes and clades of avian or swine origin influenza viruses circulating world-wide at any one time necessitates the continuous generation of CVVs to provide an advanced starting point should a novel zoonotic virus cross the species barrier and cause a pandemic. Furthermore, the evolution and diversity of novel influenza viruses that cause zoonotic infections requires ongoing monitoring and surveillance, and, when a lack of antigenic match between circulating viruses and available CVVs is identified, the production of new CVVs. Pandemic guidelines developed by the WHO Global Influenza Program govern the design and preparation of reverse genetics-derived CVVs, which must undergo numerous safety and quality tests prior to human use. Confirmation of reassortant CVV attenuation of virulence in ferrets relative to wild-type virus represents one of these critical steps, yet there is a paucity of information available regarding the relative degree of attenuation achieved by WHO-recommended CVVs developed against novel viruses with pandemic potential. To better understand the degree of CVV attenuation in the ferret model, we examined the relative virulence of six A/Puerto Rico/8/1934-based CVVs encompassing five different influenza A subtypes (H2N3, H5N1, H5N2, H5N8, and H7N9) compared with the respective wild-type virus in ferrets. Despite varied virulence of wild-type viruses in the ferret, all CVVs examined showed reductions in morbidity and viral shedding in upper respiratory tract tissues. Furthermore, unlike the wild-type counterparts, none of the CVVs spread to extrapulmonary tissues during the acute phase of infection. While the magnitude of virus attenuation varied between virus subtypes, collectively we show the reliable and reproducible attenuation of CVVs that have the A/Puerto Rico/9/1934 backbone

Pathogenicity testing of influenza candidate vaccine viruses in the ferret model

PubMed Central

Belser, Jessica A.; Johnson, Adam; Pulit-Penaloza, Joanna A.; Pappas, Claudia; Pearce, Melissa B.; Tzeng, Wen-Pin; Hossain, M. Jaber; Ridenour, Callie; Wang, Li; Chen, Li-Mei; Wentworth, David E.; Katz, Jacqueline M.; Maines, Taronna R.; Tumpey, Terrence M.

2018-01-01

The development of influenza candidate vaccine viruses (CVVs) for pre-pandemic vaccine production represents a critical step in pandemic preparedness. The multiple subtypes and clades of avian or swine origin influenza viruses circulating world-wide at any one time necessitates the continuous generation of CVVs to provide an advanced starting point should a novel zoonotic virus cross the species barrier and cause a pandemic. Furthermore, the evolution and diversity of novel influenza viruses that cause zoonotic infections requires ongoing monitoring and surveillance, and, when a lack of antigenic match between circulating viruses and available CVVs is identified, the production of new CVVs. Pandemic guidelines developed by the WHO Global Influenza Program govern the design and preparation of reverse genetics-derived CVVs, which must undergo numerous safety and quality tests prior to human use. Confirmation of reassortant CVV attenuation of virulence in ferrets relative to wild-type virus represents one of these critical steps, yet there is a paucity of information available regarding the relative degree of attenuation achieved by WHO-recommended CVVs developed against novel viruses with pandemic potential. To better understand the degree of CVV attenuation in the ferret model, we examined the relative virulence of six A/Puerto Rico/8/1934-based CVVs encompassing five different influenza A subtypes (H2N3, H5N1, H5N2, H5N8, and H7N9) compared with the respective wild-type virus in ferrets. Despite varied virulence of wild-type viruses in the ferret, all CVVs examined showed reductions in morbidity and viral shedding in upper respiratory tract tissues. Furthermore, unlike the wild-type counterparts, none of the CVVs spread to extrapulmonary tissues during the acute phase of infection. While the magnitude of virus attenuation varied between virus subtypes, collectively we show the reliable and reproducible attenuation of CVVs that have the A/Puerto Rico/9/1934 backbone

Potential for North American mosquitoes to transmit Rift Valley fever virus

USDA-ARS?s Scientific Manuscript database

The recent outbreaks of disease caused by Rift Valley fever virus (RVFV) in Kenya, Mauritania, Yemen, Tanzania, Somalia, and Madagascar indicate the potential for RVFV to cause severe disease in both humans and domestic animals and its potential to be introduced into new areas, possibly even North A...

Single-cycle replicable Rift Valley fever virus mutants as safe vaccine candidates

PubMed Central

Terasaki, Kaori; Tercero, Breanna R.; Makino, Shinji

2015-01-01

Rift Valley fever virus (RVFV) is an arbovirus circulating between ruminants and mosquitoes to maintain its enzootic cycle. Humans are infected with RVFV through mosquito bites or direct contact with materials of infected animals. The virus causes Rift Valley fever, which was first recognized in the Great Rift Valley of Kenya in 1931. RVFV is characterized by a febrile illness resulting in a high rate of abortions in ruminants and an acute febrile illness, followed by fatal hemorrhagic fever and encephalitis in humans. Initially, the virus was restricted to the eastern region of Africa, but the disease has now spread to southern and western Africa, as well as outside of the African continent, e.g., Madagascar, Saudi Arabia and Yemen. There is a serious concern that the virus may spread to other areas, such as North America and Europe. As vaccination is an effective tool to control RVFV epidemics, formalin-inactivated vaccines and live-attenuated RVFV vaccines have been used in endemic areas. The formalin-inactivated vaccines require boosters for effective protection, whereas the live-attenuated vaccines enable the induction of protective immunity by a single vaccination. However, the use of live-attenuated RVFV vaccines for large human populations having a varied health status is of concern, because of these vaccines’ residual neuro-invasiveness and neurovirulence. Recently, novel vaccine candidates have been developed using replication-defective RVFV that can undergo only a single round of replication in infected cells. The single-cycle replicable RVFV does not cause systemic infection in immunized hosts, but enables the conferring of protective immunity. This review summarizes the properties of various RVFV vaccines and recent progress on the development of the single-cycle replicable RVFV vaccines. PMID:26022573

Single-cycle replicable Rift Valley fever virus mutants as safe vaccine candidates.

PubMed

Terasaki, Kaori; Tercero, Breanna R; Makino, Shinji

2016-05-02

Rift Valley fever virus (RVFV) is an arbovirus circulating between ruminants and mosquitoes to maintain its enzootic cycle. Humans are infected with RVFV through mosquito bites or direct contact with materials of infected animals. The virus causes Rift Valley fever (RVF), which was first recognized in the Great Rift Valley of Kenya in 1931. RVF is characterized by a febrile illness resulting in a high rate of abortions in ruminants and an acute febrile illness, followed by fatal hemorrhagic fever and encephalitis in humans. Initially, the virus was restricted to the eastern region of Africa, but the disease has now spread to southern and western Africa, as well as outside of the African continent, e.g., Madagascar, Saudi Arabia and Yemen. There is a serious concern that the virus may spread to other areas, such as North America and Europe. As vaccination is an effective tool to control RVFV epidemics, formalin-inactivated vaccines and live-attenuated RVFV vaccines have been used in endemic areas. The formalin-inactivated vaccines require boosters for effective protection, whereas the live-attenuated vaccines enable the induction of protective immunity by a single vaccination. However, the use of live-attenuated RVFV vaccines for large human populations having a varied health status is of concern, because of these vaccines' residual neuro-invasiveness and neurovirulence. Recently, novel vaccine candidates have been developed using replication-defective RVFV that can undergo only a single round of replication in infected cells. The single-cycle replicable RVFV does not cause systemic infection in immunized hosts, but enables the conferring of protective immunity. This review summarizes the properties of various RVFV vaccines and recent progress on the development of the single-cycle replicable RVFV vaccines. Copyright © 2015 Elsevier B.V. All rights reserved.

Potential for autoimmune pathogenesis of Rift Valley Fever virus retinitis.

PubMed

Newman-Gerhardt, Shoshana; Muiruri, Samuel; Muchiri, Eric; Peters, Clarence J; Morrill, John; Lucas, Alexander H; King, Charles H; Kazura, James; LaBeaud, Angelle Desiree

2013-09-01

Rift Valley Fever (RVF) is a significant threat to human health because it can progress to retinitis, encephalitis, and hemorrhagic fever. The timing of onset of Rift Valley Fever virus (RVFV) retinitis suggests an autoimmune origin. To determine whether RVFV retinitis is associated with increased levels of IgG against retinal tissue, we measured and compared levels of IgG against healthy human eye tissue by immunohistochemical analysis. We found that serum samples from RVFV-exposed Kenyans with retinitis (n = 8) were slightly more likely to have antibodies against retinal tissue than control populations, but the correlation was not statistically significant. Further investigation into the possible immune pathogenesis of RVFV retinitis could lead to improved therapies to prevent or treat this severe complication.

Potential for Autoimmune Pathogenesis of Rift Valley Fever Virus Retinitis

PubMed Central

Newman-Gerhardt, Shoshana; Muiruri, Samuel; Muchiri, Eric; Peters, Clarence J.; Morrill, John; Lucas, Alexander H.; King, Charles H.; Kazura, James; LaBeaud, Angelle Desiree

2013-01-01

Rift Valley Fever (RVF) is a significant threat to human health because it can progress to retinitis, encephalitis, and hemorrhagic fever. The timing of onset of Rift Valley Fever virus (RVFV) retinitis suggests an autoimmune origin. To determine whether RVFV retinitis is associated with increased levels of IgG against retinal tissue, we measured and compared levels of IgG against healthy human eye tissue by immunohistochemical analysis. We found that serum samples from RVFV-exposed Kenyans with retinitis (n = 8) were slightly more likely to have antibodies against retinal tissue than control populations, but the correlation was not statistically significant. Further investigation into the possible immune pathogenesis of RVFV retinitis could lead to improved therapies to prevent or treat this severe complication. PMID:23918215

A Glycoprotein Subunit Vaccine Elicits a Strong Rift Valley Fever Virus Neutralizing Antibody Response in Sheep

USDA-ARS?s Scientific Manuscript database

Rift Valley fever virus (RVFV), a member of the Bunyaviridae family, is a mosquito-borne zoonotic pathogen that causes serious morbidity and mortality in livestock and humans. The recent spread of the virus beyond its traditional endemic boundaries in Africa to the Arabian Peninsula coupled with the...

Potential for North American Mosquitoes (Diptera: Culicidae) to Transmit Rift Valley Fever Virus

USDA-ARS?s Scientific Manuscript database

To determine which biting insects should be targeted for control should Rift Valley fever virus (RVFV) be detected in North America, we evaluated Culex erraticus, Culex erythrothorax, Culex pipiens, Culex quinquefasciatus, Culex tarsalis, Aedes dorsalis, Aedes vexans, Anopheles quadrimaculatus, and ...

Temperature-sensitive mutations for live-attenuated Rift Valley fever vaccines: implications from other RNA viruses

PubMed Central

Nishiyama, Shoko; Ikegami, Tetsuro

2015-01-01

Rift Valley fever (RVF) is a mosquito-borne zoonotic disease endemic to the African continent. RVF is characterized by high rate of abortions in ruminants and hemorrhagic fever, encephalitis, or blindness in humans. RVF is caused by the Rift Valley fever virus (RVFV: genus Phlebovirus, family Bunyaviridae). Vaccination is the only known effective strategy to prevent the disease, but there are no licensed RVF vaccines available for humans. A live-attenuated vaccine candidate derived from the wild-type pathogenic Egyptian ZH548 strain, MP-12, has been conditionally licensed for veterinary use in the U.S. MP-12 displays a temperature-sensitive (ts) phenotype and does not replicate at 41°C. The ts mutation limits viral replication at a specific body temperature and may lead to an attenuation of the virus. Here we will review well-characterized ts mutations for RNA viruses, and further discuss the potential in designing novel live-attenuated vaccines for RVF. PMID:26322023

Rift Valley Fever Virus among Wild Ruminants, Etosha National Park, Namibia, 2011.

PubMed

Capobianco Dondona, Andrea; Aschenborn, Ortwin; Pinoni, Chiara; Di Gialleonardo, Luigina; Maseke, Adrianatus; Bortone, Grazia; Polci, Andrea; Scacchia, Massimo; Molini, Umberto; Monaco, Federica

2016-01-01

After a May 2011 outbreak of Rift Valley fever among livestock northeast of Etosha National Park, Namibia, wild ruminants in the park were tested for the virus. Antibodies were detected in springbok, wildebeest, and black-faced impala, and viral RNA was detected in springbok. Seroprevalence was high, and immune response was long lasting.

Rift Valley fever virus (Bunyaviridae: Phlebovirus): an update on pathogenesis, molecular epidemiology, vectors, diagnostics and prevention

PubMed Central

Pepin, Michel; Bouloy, Michèle; Bird, Brian H.; Kemp, Alan; Paweska, Janusz

2010-01-01

Rift Valley fever (RVF) virus is an arbovirus in the Bunyaviridae family that, from phylogenetic analysis, appears to have first emerged in the mid-19th century and was only identified at the begininning of the 1930s in the Rift Valley region of Kenya. Despite being an arbovirus with a relatively simple but temporally and geographically stable genome, this zoonotic virus has already demonstrated a real capacity for emerging in new territories, as exemplified by the outbreaks in Egypt (1977), Western Africa (1988) and the Arabian Peninsula (2000), or for re-emerging after long periods of silence as observed very recently in Kenya and South Africa. The presence of competent vectors in countries previously free of RVF, the high viral titres in viraemic animals and the global changes in climate, travel and trade all contribute to make this virus a threat that must not be neglected as the consequences of RVF are dramatic, both for human and animal health. In this review, we present the latest advances in RVF virus research. In spite of this renewed interest, aspects of the epidemiology of RVF virus are still not fully understood and safe, effective vaccines are still not freely available for protecting humans and livestock against the dramatic consequences of this virus. PMID:21188836

Generation and characterization of monoclonal antibodies against Rift Valley fever virus nucleoprotein.

PubMed

Fafetine, J M; Domingos, A; Antunes, S; Esteves, A; Paweska, J T; Coetzer, J A W; Rutten, V P M G; Neves, L

2013-11-01

Due to the unpredictable and explosive nature of Rift Valley fever (RVF) outbreaks, rapid and accurate diagnostic assays for low-resource settings are urgently needed. To improve existing diagnostic assays, monoclonal antibodies (MAbs) specific for the nucleocapsid protein of RVF virus (RVFV) were produced and characterized. Four IgG2a MAbs showed specific binding to denatured nucleocapsid protein, both from a recombinant source and from inactivated RVFV, in Western blot analysis and in an enzyme-linked immunosorbent assay (ELISA). Cross-reactivity with genetically related and non-related arboviruses including Bunyamwera and Calovo viruses (Bunyaviridae family), West Nile and Dengue-2 viruses (Flaviviridae family), and Sindbis and Chikungunya viruses (Togaviridae family) was not detected. These MAbs represent a useful tool for the development of rapid diagnostic assays for early recognition of RVF. © 2013 Blackwell Verlag GmbH.

Factors Affecting the Ability of American Mosquitoes to Transmit Rift Valley Fever Virus

USDA-ARS?s Scientific Manuscript database

The recent outbreaks of disease caused by Rift Valley fever virus (RVFV) in Kenya, Mauritania, Yemen, Tanzania, Somalia, and Madagascar indicate the potential for RVFV to cause severe disease in both humans and domestic animals and its potential to be introduced into new areas, including North Ameri...

Mouse model for the Rift Valley fever virus MP12 strain infection.

PubMed

Lang, Yuekun; Henningson, Jamie; Jasperson, Dane; Li, Yonghai; Lee, Jinhwa; Ma, Jingjiao; Li, Yuhao; Cao, Nan; Liu, Haixia; Wilson, William; Richt, Juergen; Ruder, Mark; McVey, Scott; Ma, Wenjun

2016-11-15

Rift Valley fever virus (RVFV), a Category A pathogen and select agent, is the causative agent of Rift Valley fever. To date, no fully licensed vaccine is available in the U.S. for human or animal use and effective antiviral drugs have not been identified. The RVFV MP12 strain is conditionally licensed for use for veterinary purposes in the U.S. which was excluded from the select agent rule of Health and Human Services and the U.S. Department of Agriculture. The MP12 vaccine strain is commonly used in BSL-2 laboratories that is generally not virulent in mice. To establish a small animal model that can be used in a BSL-2 facility for antiviral drug development, we investigated susceptibility of six mouse strains (129S6/SvEv, STAT-1 KO, 129S1/SvlmJ, C57BL/6J, NZW/LacJ, BALB/c) to the MP12 virus infection via an intranasal inoculation route. Severe weight loss, obvious clinical and neurologic signs, and 50% mortality was observed in the STAT-1 KO mice, whereas the other 5 mouse strains did not display obvious and/or severe disease. Virus replication and histopathological lesions were detected in brain and liver of MP12-infected STAT-1 KO mice that developed the acute-onset hepatitis and delayed-onset encephalitis. In conclusion, the STAT-1 KO mouse strain is susceptible to MP12 virus infection, indicating that it can be used to investigate RVFV antivirals in a BSL-2 environment. Copyright © 2016 Elsevier B.V. All rights reserved.

Experimental Infection of Calves by Two Genetically-Distinct Strains of Rift Valley Fever Virus.

PubMed

Wilson, William C; Davis, A Sally; Gaudreault, Natasha N; Faburay, Bonto; Trujillo, Jessie D; Shivanna, Vinay; Sunwoo, Sun Young; Balogh, Aaron; Endalew, Abaineh; Ma, Wenjun; Drolet, Barbara S; Ruder, Mark G; Morozov, Igor; McVey, D Scott; Richt, Juergen A

2016-05-23

Recent outbreaks of Rift Valley fever in ruminant livestock, characterized by mass abortion and high mortality rates in neonates, have raised international interest in improving vaccine control strategies. Previously, we developed a reliable challenge model for sheep that improves the evaluation of existing and novel vaccines in sheep. This sheep model demonstrated differences in the pathogenesis of Rift Valley fever virus (RVFV) infection between two genetically-distinct wild-type strains of the virus, Saudi Arabia 2001 (SA01) and Kenya 2006 (Ken06). Here, we evaluated the pathogenicity of these two RVFV strains in mixed breed beef calves. There was a transient increase in rectal temperatures with both virus strains, but this clinical sign was less consistent than previously reported with sheep. Three of the five Ken06-infected animals had an early-onset viremia, one day post-infection (dpi), with viremia lasting at least three days. The same number of SA01-infected animals developed viremia at 2 dpi, but it only persisted through 3 dpi in one animal. The average virus titer for the SA01-infected calves was 1.6 logs less than for the Ken06-infected calves. Calves, inoculated with either strain, seroconverted by 5 dpi and showed time-dependent increases in their virus-neutralizing antibody titers. Consistent with the results obtained in the previous sheep study, elevated liver enzyme levels, more severe liver pathology and higher virus titers occurred with the Ken06 strain as compared to the SA01 strain. These results demonstrate the establishment of a virulent challenge model for vaccine evaluation in calves.

Rift Valley fever virus MP-12 vaccine encoding Toscana virus NSs retains neuroinvasiveness in mice.

PubMed

Indran, Sabarish V; Lihoradova, Olga A; Phoenix, Inaia; Lokugamage, Nandadeva; Kalveram, Birte; Head, Jennifer A; Tigabu, Bersabeh; Smith, Jennifer K; Zhang, Lihong; Juelich, Terry L; Gong, Bin; Freiberg, Alexander N; Ikegami, Tetsuro

2013-07-01

Rift Valley fever is a mosquito-borne zoonotic disease endemic to sub-Saharan Africa. Rift Valley fever virus (RVFV; genus Phlebovirus, family Bunyaviridae) causes high rates of abortion and fetal malformation in pregnant ruminants, and haemorrhagic fever, neurological disorders or blindness in humans. The MP-12 strain is a highly efficacious and safe live-attenuated vaccine candidate for both humans and ruminants. However, MP-12 lacks a marker to differentiate infected from vaccinated animals. In this study, we originally aimed to characterize the efficacy of a recombinant RVFV MP-12 strain encoding Toscana virus (TOSV) NSs gene in place of MP-12 NSs (rMP12-TOSNSs). TOSV NSs promotes the degradation of dsRNA-dependent protein kinase (PKR) and inhibits interferon-β gene up-regulation without suppressing host general transcription. Unexpectedly, rMP12-TOSNSs increased death in vaccinated outbred mice and inbred BALB/c or C57BL/6 mice. Immunohistochemistry showed diffusely positive viral antigens in the thalamus, hypothalamus and brainstem, including the medulla. No viral antigens were detected in spleen or liver, which is similar to the antigen distribution of moribund mice infected with MP-12. These results suggest that rMP12-TOSNSs retains neuroinvasiveness in mice. Our findings demonstrate that rMP12-TOSNSs causes neuroinvasion without any hepatic disease and will be useful for studying the neuroinvasion mechanism of RVFV and TOSV.

Rift Valley fever virus MP-12 vaccine encoding Toscana virus NSs retains neuroinvasiveness in mice

PubMed Central

Indran, Sabarish V.; Lihoradova, Olga A.; Phoenix, Inaia; Lokugamage, Nandadeva; Kalveram, Birte; Head, Jennifer A.; Tigabu, Bersabeh; Smith, Jennifer K.; Zhang, Lihong; Juelich, Terry L.; Gong, Bin; Freiberg, Alexander N.

2013-01-01

Rift Valley fever is a mosquito-borne zoonotic disease endemic to sub-Saharan Africa. Rift Valley fever virus (RVFV; genus Phlebovirus, family Bunyaviridae) causes high rates of abortion and fetal malformation in pregnant ruminants, and haemorrhagic fever, neurological disorders or blindness in humans. The MP-12 strain is a highly efficacious and safe live-attenuated vaccine candidate for both humans and ruminants. However, MP-12 lacks a marker to differentiate infected from vaccinated animals. In this study, we originally aimed to characterize the efficacy of a recombinant RVFV MP-12 strain encoding Toscana virus (TOSV) NSs gene in place of MP-12 NSs (rMP12-TOSNSs). TOSV NSs promotes the degradation of dsRNA-dependent protein kinase (PKR) and inhibits interferon-β gene up-regulation without suppressing host general transcription. Unexpectedly, rMP12-TOSNSs increased death in vaccinated outbred mice and inbred BALB/c or C57BL/6 mice. Immunohistochemistry showed diffusely positive viral antigens in the thalamus, hypothalamus and brainstem, including the medulla. No viral antigens were detected in spleen or liver, which is similar to the antigen distribution of moribund mice infected with MP-12. These results suggest that rMP12-TOSNSs retains neuroinvasiveness in mice. Our findings demonstrate that rMP12-TOSNSs causes neuroinvasion without any hepatic disease and will be useful for studying the neuroinvasion mechanism of RVFV and TOSV. PMID:23515022

Persistence of Rift Valley fever virus in East Africa

NASA Astrophysics Data System (ADS)

Gachohi, J.; Hansen, F.; Bett, B.; Kitala, P.

2012-04-01

Rift Valley fever virus (RVFv) is a mosquito-borne pathogen of livestock, wildlife and humans that causes severe outbreaks in intervals of several years. One of the open questions is how the virus persists between outbreaks. We developed a spatially-explicit, individual-based simulation model of the RVFv transmission dynamics to investigate this question. The model, is based on livestock and mosquito population dynamics. Spatial aspects are explicitly represented by a set of grid cells that represent mosquito breeding sites. A grid cell measures 500 by 500m and the model considers a grid of 100 by 100 grid cells; the model thus operates on the regional scale of 2500km2. Livestock herds move between grid cells, and provide connectivity between the cells. The model is used to explore the spatio-temporal dynamics of RVFv persistence in absence of a wildlife reservoir in an east African semi-arid context. Specifically, the model assesses the importance of local virus persistence in mosquito breeding sites relative to global virus persistence mitigated by movement of hosts. Local persistence is determined by the length of time the virus remains in a mosquito breeding site once introduced. In the model, this is a function of the number of mosquitoes that emerge infected and their lifespan. Global persistence is determined by the level of connectivity between isolated grid cells. Our work gives insights into the ecological and epidemiological conditions under which RVFv persists. The implication for disease surveillance and management are discussed.

Recent advances in the development of antiviral therapeutics for Rift Valley fever virus infection.

PubMed

Atkins, Colm; Freiberg, Alexander N

2017-11-01

Rift Valley fever virus (RVFV) is a mosquito-borne bunyavirus endemic to sub-Saharan Africa and the Arabian Peninsula and the etiological agent of Rift Valley fever. Rift Valley fever is a disease of major public health and economic concern, affecting livestock and humans. In ruminants, RVFV infection is characterized by high mortality rates in newborns and near 100% abortion rates in pregnant animals. Infection in humans is typically manifested as a self-limiting febrile illness, but can lead to severe and fatal hepatitis, encephalitis, hemorrhagic fever or retinitis with partial or complete blindness. Currently, there are no specific treatment options available for RVFV infection. This review presents a summary of the therapeutic approaches that have been explored on the treatment of RVFV infection.

Rift Valley fever virus: A review of diagnosis and vaccination, and implications for emergence in Europe.

PubMed

Mansfield, Karen L; Banyard, Ashley C; McElhinney, Lorraine; Johnson, Nicholas; Horton, Daniel L; Hernández-Triana, Luis M; Fooks, Anthony R

2015-10-13

Rift Valley fever virus (RVFV) is a mosquito-borne virus, and is the causative agent of Rift Valley fever (RVF), a zoonotic disease characterised by an increased incidence of abortion or foetal malformation in ruminants. Infection in humans can also lead to clinical manifestations that in severe cases cause encephalitis or haemorrhagic fever. The virus is endemic throughout much of the African continent. However, the emergence of RVFV in the Middle East, northern Egypt and the Comoros Archipelago has highlighted that the geographical range of RVFV may be increasing, and has led to the concern that an incursion into Europe may occur. At present, there is a limited range of veterinary vaccines available for use in endemic areas, and there is no licensed human vaccine. In this review, the methods available for diagnosis of RVFV infection, the current status of vaccine development and possible implications for RVFV emergence in Europe, are discussed. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

RNA Interference Restricts Rift Valley Fever Virus in Multiple Insect Systems.

PubMed

Dietrich, Isabelle; Jansen, Stephanie; Fall, Gamou; Lorenzen, Stephan; Rudolf, Martin; Huber, Katrin; Heitmann, Anna; Schicht, Sabine; Ndiaye, El Hadji; Watson, Mick; Castelli, Ilaria; Brennan, Benjamin; Elliott, Richard M; Diallo, Mawlouth; Sall, Amadou A; Failloux, Anna-Bella; Schnettler, Esther; Kohl, Alain; Becker, Stefanie C

2017-01-01

The emerging bunyavirus Rift Valley fever virus (RVFV) is transmitted to humans and livestock by a large number of mosquito species. RNA interference (RNAi) has been characterized as an important innate immune defense mechanism used by mosquitoes to limit replication of positive-sense RNA flaviviruses and togaviruses; however, little is known about its role against negative-strand RNA viruses such as RVFV. We show that virus-specific small RNAs are produced in infected mosquito cells, in Drosophila melanogaster cells, and, most importantly, also in RVFV vector mosquitoes. By addressing the production of small RNAs in adult Aedes sp. and Culex quinquefasciatus mosquitoes, we showed the presence of virus-derived Piwi-interacting RNAs (piRNAs) not only in Aedes sp. but also in C. quinquefasciatus mosquitoes, indicating that antiviral RNA interference in C. quinquefasciatus mosquitoes is similar to the described activities of RNAi in Aedes sp. mosquitoes. We also show that these have antiviral activity, since silencing of RNAi pathway effectors enhances viral replication. Moreover, our data suggest that RVFV does not encode a suppressor of RNAi. These findings point toward a significant role of RNAi in the control of RVFV in mosquitoes. IMPORTANCE Rift Valley fever virus (RVFV; Phlebovirus , Bunyaviridae ) is an emerging zoonotic mosquito-borne pathogen of high relevance for human and animal health. Successful strategies of intervention in RVFV transmission by its mosquito vectors and the prevention of human and veterinary disease rely on a better understanding of the mechanisms that govern RVFV-vector interactions. Despite its medical importance, little is known about the factors that govern RVFV replication, dissemination, and transmission in the invertebrate host. Here we studied the role of the antiviral RNA interference immune pathways in the defense against RVFV in natural vector mosquitoes and mosquito cells and draw comparisons to the model insect Drosophila

RNA Interference Restricts Rift Valley Fever Virus in Multiple Insect Systems

PubMed Central

Jansen, Stephanie; Fall, Gamou; Lorenzen, Stephan; Rudolf, Martin; Huber, Katrin; Heitmann, Anna; Schicht, Sabine; Ndiaye, El Hadji; Watson, Mick; Castelli, Ilaria; Elliott, Richard M.; Diallo, Mawlouth; Sall, Amadou A.; Failloux, Anna-Bella; Schnettler, Esther

2017-01-01

ABSTRACT The emerging bunyavirus Rift Valley fever virus (RVFV) is transmitted to humans and livestock by a large number of mosquito species. RNA interference (RNAi) has been characterized as an important innate immune defense mechanism used by mosquitoes to limit replication of positive-sense RNA flaviviruses and togaviruses; however, little is known about its role against negative-strand RNA viruses such as RVFV. We show that virus-specific small RNAs are produced in infected mosquito cells, in Drosophila melanogaster cells, and, most importantly, also in RVFV vector mosquitoes. By addressing the production of small RNAs in adult Aedes sp. and Culex quinquefasciatus mosquitoes, we showed the presence of virus-derived Piwi-interacting RNAs (piRNAs) not only in Aedes sp. but also in C. quinquefasciatus mosquitoes, indicating that antiviral RNA interference in C. quinquefasciatus mosquitoes is similar to the described activities of RNAi in Aedes sp. mosquitoes. We also show that these have antiviral activity, since silencing of RNAi pathway effectors enhances viral replication. Moreover, our data suggest that RVFV does not encode a suppressor of RNAi. These findings point toward a significant role of RNAi in the control of RVFV in mosquitoes. IMPORTANCE Rift Valley fever virus (RVFV; Phlebovirus, Bunyaviridae) is an emerging zoonotic mosquito-borne pathogen of high relevance for human and animal health. Successful strategies of intervention in RVFV transmission by its mosquito vectors and the prevention of human and veterinary disease rely on a better understanding of the mechanisms that govern RVFV-vector interactions. Despite its medical importance, little is known about the factors that govern RVFV replication, dissemination, and transmission in the invertebrate host. Here we studied the role of the antiviral RNA interference immune pathways in the defense against RVFV in natural vector mosquitoes and mosquito cells and draw comparisons to the model insect

Potential for Stable Flies and House Flies (Diptera: Muscidae) to Transmit Rift Valley Fever Virus

DTIC Science & Technology

2010-01-01

14. ABSTRACT Rift Valley fever ( RVF ), a disease of ruminants and humans, has been responsible for large outbreaks in Africa that have resulted in...regions. Although RVF virus (RVFV) is normally transmitted by mosquitoes, we wanted to determine the potential for this virus to replicate in 2 of...of a RVF outbreak. Other Stomoxys species present in Africa and elsewhere may also play similar roles. 15. SUBJECT TERMS 16. SECURITY CLASSIFICATION

Rift Valley fever in Namibia, 2010.

PubMed

Monaco, Federica; Pinoni, Chiara; Cosseddu, Gian Mario; Khaiseb, Siegfried; Calistri, Paolo; Molini, Umberto; Bishi, Alec; Conte, Annamaria; Scacchia, Massimo; Lelli, Rossella

2013-12-01

During May-July 2010 in Namibia, outbreaks of Rift Valley fever were reported to the National Veterinary Service. Analysis of animal specimens confirmed virus circulation on 7 farms. Molecular characterization showed that all outbreaks were caused by a strain of Rift Valley fever virus closely related to virus strains responsible for outbreaks in South Africa during 2009-2010.

Fatal Infection with Murray Valley Encephalitis Virus Imported from Australia to Canada, 2011.

PubMed

Niven, Daniel J; Afra, Kevin; Iftinca, Mircea; Tellier, Raymond; Fonseca, Kevin; Kramer, Andreas; Safronetz, David; Holloway, Kimberly; Drebot, Michael; Johnson, Andrew S

2017-02-01

Murray Valley encephalitis virus (MVEV), a flavivirus belonging to the Japanese encephalitis serogroup, can cause severe clinical manifestations in humans. We report a fatal case of MVEV infection in a young woman who returned from Australia to Canada. The differential diagnosis for travel-associated encephalitis should include MVEV, particularly during outbreak years.

Potential for mosquitoes (Diptera: Culicidae) from Florida to transmit rift valley fever virus

USDA-ARS?s Scientific Manuscript database

We evaluated 8 species of mosquitoes collected in Florida to determine which of these should be targeted for control should Rift Valley fever virus (RVFV) be detected in North America. Female mosquitoes that had fed on adult hamsters inoculated with RVFV were incubated for 7-21 d at 26°C, allowed to...

Experimental Infection of Calves by Two Genetically-Distinct Strains of Rift Valley Fever Virus

PubMed Central

Wilson, William C.; Davis, A. Sally; Gaudreault, Natasha N.; Faburay, Bonto; Trujillo, Jessie D.; Shivanna, Vinay; Sunwoo, Sun Young; Balogh, Aaron; Endalew, Abaineh; Ma, Wenjun; Drolet, Barbara S.; Ruder, Mark G.; Morozov, Igor; McVey, D. Scott; Richt, Juergen A.

2016-01-01

Recent outbreaks of Rift Valley fever in ruminant livestock, characterized by mass abortion and high mortality rates in neonates, have raised international interest in improving vaccine control strategies. Previously, we developed a reliable challenge model for sheep that improves the evaluation of existing and novel vaccines in sheep. This sheep model demonstrated differences in the pathogenesis of Rift Valley fever virus (RVFV) infection between two genetically-distinct wild-type strains of the virus, Saudi Arabia 2001 (SA01) and Kenya 2006 (Ken06). Here, we evaluated the pathogenicity of these two RVFV strains in mixed breed beef calves. There was a transient increase in rectal temperatures with both virus strains, but this clinical sign was less consistent than previously reported with sheep. Three of the five Ken06-infected animals had an early-onset viremia, one day post-infection (dpi), with viremia lasting at least three days. The same number of SA01-infected animals developed viremia at 2 dpi, but it only persisted through 3 dpi in one animal. The average virus titer for the SA01-infected calves was 1.6 logs less than for the Ken06-infected calves. Calves, inoculated with either strain, seroconverted by 5 dpi and showed time-dependent increases in their virus-neutralizing antibody titers. Consistent with the results obtained in the previous sheep study, elevated liver enzyme levels, more severe liver pathology and higher virus titers occurred with the Ken06 strain as compared to the SA01 strain. These results demonstrate the establishment of a virulent challenge model for vaccine evaluation in calves. PMID:27223298

Development of a Rift Valley fever virus viremia challenge model in sheep and goats

USDA-ARS?s Scientific Manuscript database

Rift valley fever virus (RVFV), a member of the family Bunyaviridae, causes severe to fatal disease in newborn ruminants, as well as abortions in pregnant animals; both preventable by vaccination. Availability of a challenge model is a pre-requisite for vaccine efficacy trials. Several modes of ino...

Rift Valley fever virus-infected mosquito ova and associated pathology: possible implications for endemic maintenance

USDA-ARS?s Scientific Manuscript database

Background: Endemic/enzootic maintenance mechanisms like vertical transmission, pathogen passage from infected adults to their offspring, are central in the epidemiology of zoonotic pathogens. In Kenya, Rift Valley fever virus (RVFV) may be maintained by vertical transmission in ground-pool mosquit...

A Replication-incompetent Rift Valley Fever Vaccine: Chimeric Virus-like Particles Protect Mice and Rats Against Lethal Challenge

PubMed Central

Mandell, Robert B.; Koukuntla, Ramesh; Mogler, Laura J. K.; Carzoli, Andrea K.; Freiberg, Alexander N.; Holbrook, Michael R.; Martin, Brian K.; Staplin, William R.; Vahanian, Nicholas N.; Link, Charles J.; Flick, Ramon

2009-01-01

Virus-like particles (VLPs) present viral antigens in a native conformation and are effectively recognized by the immune system and therefore are considered as suitable and safe vaccine candidates against many viral diseases. Here we demonstrate that chimeric VLPs containing Rift Valley fever virus (RVFV) glycoproteins GN and GC, nucleoprotein N and the gag protein of Moloney murine leukemia virus represent an effective vaccine candidate against Rift Valley fever, a deadly disease in humans and livestock. Long-lasting humoral and cellular immune responses are demonstrated in a mouse model by the analysis of neutralizing antibody titers and cytokine secretion profiles. Vaccine efficacy studies were performed in mouse and rat lethal challenge models resulting in high protection rates. Taken together, these results demonstrate that replication-incompetent chimeric RVF VLPs are an efficient RVFV vaccine candidate. PMID:19932911

Single-particle cryo-electron microscopy of Rift Valley fever virus

PubMed Central

Sherman, Michael B.; Freiberg, Alexander N.; Holbrook, Michael R.; Watowich, Stanley J.

2009-01-01

Rift Valley fever virus (RVFV; Bunyaviridae; Phlebovirus) is an emerging human veterinary pathogen causing acute hepatitis in ruminants and has the potential to Single-particle cryo-EM reconstruction of RVFV MP-12 hemorrhagic fever in humans. We report a three-dimensional reconstruction of RVFV vaccine strain MP-12 (RVFV MP-12) by cryo-electron microcopy using icosahedral symmetry of individual virions. Although the genomic core of RVFV MP-12 is apparently poorly ordered, the glycoproteins on the virus surface are highly symmetric and arranged on a T=12 icosahedral lattice. Our RVFV MP-12 structure allowed clear identification of inter-capsomer contacts and definition of possible glycoprotein arrangements within capsomers. This structure provides a detailed model for phleboviruses, opens new avenues for high-resolution structural studies of the bunyavirus family, and aids the design of antiviral diagnostics and effective subunit-vaccines. PMID:19304307

Single-particle cryo-electron microscopy of Rift Valley fever virus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sherman, Michael B.; Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, TX 77555; Freiberg, Alexander N.

2009-04-25

Rift Valley fever virus (RVFV; Bunyaviridae; Phlebovirus) is an emerging human and veterinary pathogen causing acute hepatitis in ruminants and has the potential to cause hemorrhagic fever in humans. We report a three-dimensional reconstruction of RVFV vaccine strain MP-12 (RVFV MP-12) by cryo-electron microcopy using icosahedral symmetry of individual virions. Although the genomic core of RVFV MP-12 is apparently poorly ordered, the glycoproteins on the virus surface are highly symmetric and arranged on a T = 12 icosahedral lattice. Our RVFV MP-12 structure allowed clear identification of inter-capsomer contacts and definition of possible glycoprotein arrangements within capsomers. This structure providesmore » a detailed model for phleboviruses, opens new avenues for high-resolution structural studies of the bunyavirus family, and aids the design of antiviral diagnostics and effective subunit vaccines.« less

Biology and Molecular Characterization of Cucurbit leaf crumple virus, an Emergent Cucurbit-Infecting Begomovirus in the Imperial Valley of California

USDA-ARS?s Scientific Manuscript database

Cucurbit leaf crumple virus (CuLCrV) is an emergent and potentially economically important bipartite begomovirus first identified in volunteer watermelon plants in the Imperial Valley of southern California in 1998. Field surveys indicated that CuLCrV has become established in the Imperial Valley; a...

A Haploid Genetic Screen Identifies Heparan Sulfate Proteoglycans Supporting Rift Valley Fever Virus Infection.

PubMed

Riblett, Amber M; Blomen, Vincent A; Jae, Lucas T; Altamura, Louis A; Doms, Robert W; Brummelkamp, Thijn R; Wojcechowskyj, Jason A

2016-02-01

Rift Valley fever virus (RVFV) causes recurrent insect-borne epizootics throughout the African continent, and infection of humans can lead to a lethal hemorrhagic fever syndrome. Deep mutagenesis of haploid human cells was used to identify host factors required for RVFV infection. This screen identified a suite of enzymes involved in glycosaminoglycan (GAG) biogenesis and transport, including several components of the cis-oligomeric Golgi (COG) complex, one of the central components of Golgi complex trafficking. In addition, disruption of PTAR1 led to RVFV resistance as well as reduced heparan sulfate surface levels, consistent with recent observations that PTAR1-deficient cells exhibit altered Golgi complex morphology and glycosylation defects. A variety of biochemical and genetic approaches were utilized to show that both pathogenic and attenuated RVFV strains require GAGs for efficient infection on some, but not all, cell types, with the block to infection being at the level of virion attachment. Examination of other members of the Bunyaviridae family for GAG-dependent infection suggested that the interaction with GAGs is not universal among bunyaviruses, indicating that these viruses, as well as RVFV on certain cell types, employ additional unidentified virion attachment factors and/or receptors. Rift Valley fever virus (RVFV) is an emerging pathogen that can cause severe disease in humans and animals. Epizootics among livestock populations lead to high mortality rates and can be economically devastating. Human epidemics of Rift Valley fever, often initiated by contact with infected animals, are characterized by a febrile disease that sometimes leads to encephalitis or hemorrhagic fever. The global burden of the pathogen is increasing because it has recently disseminated beyond Africa, which is of particular concern because the virus can be transmitted by widely distributed mosquito species. There are no FDA-licensed vaccines or antiviral agents with activity

Efficacy of a recombinant Rift Valley fever virus MP-12 with NSm deletion as a vaccine candidate in sheep

USDA-ARS?s Scientific Manuscript database

Rift Valley fever virus (RVFV), a mosquito-borne virus in the Bunyaviridae family and Phlebovirus genus, causes RVF, a disease of ruminants and man, endemic in Sub-Saharan African countries. However, outbreaks in Yemen and Saudi Arabia demonstrate the ability for RVFV to spread into virgin territory...

Comparison of Rift Valley fever virus replication in North American livestock and wildlife cell lines

USDA-ARS?s Scientific Manuscript database

Rift Valley fever virus (RVFV) causes outbreaks of endemic disease across Africa and the Arabian Peninsula, resulting in high morbidity and mortality among young domestic livestock, frequent abortions in pregnant animals, and potentially severe or fatal disease in humans. The possibility of RVFV spr...

77 FR 68783 - Prospective Grant of Exclusive License: Veterinary Vaccines for Rift Valley Fever Virus

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-16

... Grant of Exclusive License: Veterinary Vaccines for Rift Valley Fever Virus AGENCY: Centers for Disease... territories other than Africa, in the field of use of veterinary vaccines, to practice the inventions listed... precisely defined attenuated vaccine constructs that contain complete deletions of critical virulence...

Rift Valley fever virus infection induces activation of the NLRP3 inflammasome.

PubMed

Ermler, Megan E; Traylor, Zachary; Patel, Krupen; Schattgen, Stefan A; Vanaja, Sivapriya K; Fitzgerald, Katherine A; Hise, Amy G

2014-01-20

Inflammasome activation is gaining recognition as an important mechanism for protection during viral infection. Here, we investigate whether Rift Valley fever virus, a negative-strand RNA virus, can induce inflammasome responses and IL-1β processing in immune cells. We have determined that RVFV induces NLRP3 inflammasome activation in murine dendritic cells, and that this process is dependent upon ASC and caspase-1. Furthermore, absence of the cellular RNA helicase adaptor protein MAVS/IPS-1 significantly reduces extracellular IL-1β during infection. Finally, direct imaging using confocal microscopy shows that the MAVS protein co-localizes with NLRP3 in the cytoplasm of RVFV infected cells. © 2013 Published by Elsevier Inc.

Reduced Rift Valley fever virus infection rates in mosquitoes associated with pledget feedings.

PubMed

Turell, M J

1988-12-01

Infection rates were compared in Culex pipiens and Aedes taeniorhynchus after they fed on Rift Valley fever (RVF) viremic hamsters or ingested similar doses of RVF virus from blood-soaked pledgets. Infection rates were significantly lower for mosquitoes that ingested virus from a pledget than for those that ingested similar doses from viremic hamsters. The method used to prevent normal clot formation for the pledget feedings (i.e., defibrination by shaking with glass beads or addition of heparin) did not affect subsequent infection rates. Both inhibition of normal clot formation and freezing of virus after it had last been propagated were associated with significantly reduced infection rates with the pledget feedings. Laboratory studies using artificial feeding techniques may not give reliable estimates of the vector competence of mosquitoes for arboviruses.

Rift Valley fever virus and European mosquitoes: vector competence of Culex pipiens and Stegomyia albopicta (= Aedes albopictus).

PubMed

Brustolin, M; Talavera, S; Nuñez, A; Santamaría, C; Rivas, R; Pujol, N; Valle, M; Verdún, M; Brun, A; Pagès, N; Busquets, N

2017-12-01

Rift Valley fever (RVF) is a mosquito-borne disease caused by the Rift Valley fever virus (RVFV). Rift Valley fever affects a large number of species, including human, and has severe impact on public health and the economy, especially in African countries. The present study examined the vector competence of three different European mosquito species, Culex pipiens (Linnaeus, 1758) form molestus (Diptera: Culicidae), Culex pipiens hybrid form and Stegomyia albopicta (= Aedes albopictus) (Skuse, 1894) (Diptera: Culicidae). Mosquitoes were artificially fed with blood containing RVFV. Infection, disseminated infection and transmission efficiency were evaluated. This is the first study to assess the transmission efficiency of European mosquito species using a virulent RVFV strain. The virus disseminated in Cx. pipiens hybrid form and in S. albopicta. Moreover, infectious viral particles were isolated from saliva of both species, showing their RVFV transmission capacity. The presence of competent Cx. pipiens and S. albopicta in Spain indicates that an autochthonous outbreak of RVF may occur if the virus is introduced. These findings provide information that will help health authorities to set up efficient entomological surveillance and RVFV vector control programmes. © 2017 The Authors. Medical and Veterinary Entomology published by John Wiley & Sons Ltd on behalf of Royal Entomological Society.

Effect of environmental temperature on the vector competence of mosquitoes for Rift Valley fever virus

USDA-ARS?s Scientific Manuscript database

Environmental temperature has been shown to affect the ability of mosquitoes to transmit numerous arboviruses and for Rift Valley fever virus (RVFV) in particular. We evaluated the effect of incubation temperatures ranging from 14-26ºC on infection, dissemination, and transmission rates for Culex ta...

Isolation of deer tick virus (Powassan virus, lineage II) from Ixodes scapularis and detection of antibody in vertebrate hosts sampled in the Hudson Valley, New York State

PubMed Central

2013-01-01

Background Deer tick virus, DTV, is a genetically and ecologically distinct lineage of Powassan virus (POWV) also known as lineage II POWV. Human incidence of POW encephalitis has increased in the last 15 years potentially due to the emergence of DTV, particularly in the Hudson Valley of New York State. We initiated an extensive sampling campaign to determine whether POWV was extant throughout the Hudson Valley in tick vectors and/or vertebrate hosts. Methods More than 13,000 ticks were collected from hosts or vegetation and tested for the presence of DTV using molecular and virus isolation techniques. Vertebrate hosts of Ixodes scapularis (black-legged tick) were trapped (mammals) or netted (birds) and blood samples analyzed for the presence of neutralizing antibodies to POWV. Maximum likelihood estimates (MLE) were calculated to determine infection rates in ticks at each study site. Results Evidence of DTV was identified each year from 2007 to 2012, in nymphal and adult I. scapularis collected from the Hudson Valley. 58 tick pools were positive for virus and/or RNA. Infection rates were higher in adult ticks collected from areas east of the Hudson River. MLE limits ranged from 0.2-6.0 infected adults per 100 at sites where DTV was detected. Virginia opossums, striped skunks and raccoons were the source of infected nymphal ticks collected as replete larvae. Serologic evidence of POWV infection was detected in woodchucks (4/6), an opossum (1/6), and birds (4/727). Lineage I, prototype POWV, was not detected. Conclusions These data demonstrate widespread enzootic transmission of DTV throughout the Hudson Valley, in particular areas east of the river. High infection rates were detected in counties where recent POW encephalitis cases have been identified, supporting the hypothesis that lineage II POWV, DTV, is responsible for these human infections. PMID:24016533

Isolation of deer tick virus (Powassan virus, lineage II) from Ixodes scapularis and detection of antibody in vertebrate hosts sampled in the Hudson Valley, New York State.

PubMed

Dupuis, Alan P; Peters, Ryan J; Prusinski, Melissa A; Falco, Richard C; Ostfeld, Richard S; Kramer, Laura D

2013-07-15

Deer tick virus, DTV, is a genetically and ecologically distinct lineage of Powassan virus (POWV) also known as lineage II POWV. Human incidence of POW encephalitis has increased in the last 15 years potentially due to the emergence of DTV, particularly in the Hudson Valley of New York State. We initiated an extensive sampling campaign to determine whether POWV was extant throughout the Hudson Valley in tick vectors and/or vertebrate hosts. More than 13,000 ticks were collected from hosts or vegetation and tested for the presence of DTV using molecular and virus isolation techniques. Vertebrate hosts of Ixodes scapularis (black-legged tick) were trapped (mammals) or netted (birds) and blood samples analyzed for the presence of neutralizing antibodies to POWV. Maximum likelihood estimates (MLE) were calculated to determine infection rates in ticks at each study site. Evidence of DTV was identified each year from 2007 to 2012, in nymphal and adult I. scapularis collected from the Hudson Valley. 58 tick pools were positive for virus and/or RNA. Infection rates were higher in adult ticks collected from areas east of the Hudson River. MLE limits ranged from 0.2-6.0 infected adults per 100 at sites where DTV was detected. Virginia opossums, striped skunks and raccoons were the source of infected nymphal ticks collected as replete larvae. Serologic evidence of POWV infection was detected in woodchucks (4/6), an opossum (1/6), and birds (4/727). Lineage I, prototype POWV, was not detected. These data demonstrate widespread enzootic transmission of DTV throughout the Hudson Valley, in particular areas east of the river. High infection rates were detected in counties where recent POW encephalitis cases have been identified, supporting the hypothesis that lineage II POWV, DTV, is responsible for these human infections.

Rift Valley fever virus incorporates the 78kDa glycoprotein into virions matured in C6/36 2 mosquito cells

USDA-ARS?s Scientific Manuscript database

Rift Valley fever virus (RVFV), genus Phlebovirus, family Bunyaviridae is a zoonotic arthropod-borne virus able to transition between distant host species, causing potentially severe disease in humans and ruminants. Viral proteins are encoded by three genomic segments, with the medium M segment codi...

A Recombinant Rift Valley Fever Virus Glycoprotein Subunit Vaccine Confers Full Protection against Rift Valley Fever Challenge in Sheep.

PubMed

Faburay, Bonto; Wilson, William C; Gaudreault, Natasha N; Davis, A Sally; Shivanna, Vinay; Bawa, Bhupinder; Sunwoo, Sun Young; Ma, Wenjun; Drolet, Barbara S; Morozov, Igor; McVey, D Scott; Richt, Juergen A

2016-06-14

Rift Valley fever virus (RVFV) is a mosquito-borne zoonotic pathogen causing disease outbreaks in Africa and the Arabian Peninsula. The virus has great potential for transboundary spread due to the presence of competent vectors in non-endemic areas. There is currently no fully licensed vaccine suitable for use in livestock or humans outside endemic areas. Here we report the evaluation of the efficacy of a recombinant subunit vaccine based on the RVFV Gn and Gc glycoproteins. In a previous study, the vaccine elicited strong virus neutralizing antibody responses in sheep and was DIVA (differentiating naturally infected from vaccinated animals) compatible. In the current efficacy study, a group of sheep (n = 5) was vaccinated subcutaneously with the glycoprotein-based subunit vaccine candidate and then subjected to heterologous challenge with the virulent Kenya-128B-15 RVFV strain. The vaccine elicited high virus neutralizing antibody titers and conferred complete protection in all vaccinated sheep, as evidenced by prevention of viremia, fever and absence of RVFV-associated histopathological lesions. We conclude that the subunit vaccine platform represents a promising strategy for the prevention and control of RVFV infections in susceptible hosts.

A Recombinant Rift Valley Fever Virus Glycoprotein Subunit Vaccine Confers Full Protection against Rift Valley Fever Challenge in Sheep

PubMed Central

Faburay, Bonto; Wilson, William C.; Gaudreault, Natasha N.; Davis, A. Sally; Shivanna, Vinay; Bawa, Bhupinder; Sunwoo, Sun Young; Ma, Wenjun; Drolet, Barbara S.; Morozov, Igor; McVey, D. Scott; Richt, Juergen A.

2016-01-01

Rift Valley fever virus (RVFV) is a mosquito-borne zoonotic pathogen causing disease outbreaks in Africa and the Arabian Peninsula. The virus has great potential for transboundary spread due to the presence of competent vectors in non-endemic areas. There is currently no fully licensed vaccine suitable for use in livestock or humans outside endemic areas. Here we report the evaluation of the efficacy of a recombinant subunit vaccine based on the RVFV Gn and Gc glycoproteins. In a previous study, the vaccine elicited strong virus neutralizing antibody responses in sheep and was DIVA (differentiating naturally infected from vaccinated animals) compatible. In the current efficacy study, a group of sheep (n = 5) was vaccinated subcutaneously with the glycoprotein-based subunit vaccine candidate and then subjected to heterologous challenge with the virulent Kenya-128B-15 RVFV strain. The vaccine elicited high virus neutralizing antibody titers and conferred complete protection in all vaccinated sheep, as evidenced by prevention of viremia, fever and absence of RVFV-associated histopathological lesions. We conclude that the subunit vaccine platform represents a promising strategy for the prevention and control of RVFV infections in susceptible hosts. PMID:27296136

Rift Valley Fever Outbreak in Livestock, Mozambique, 2014.

PubMed

Fafetine, José M; Coetzee, Peter; Mubemba, Benjamin; Nhambirre, Ofélia; Neves, Luis; Coetzer, J A W; Venter, Estelle H

2016-12-01

In early 2014, abortions and death of ruminants were reported on farms in Maputo and Gaza Provinces, Mozambique. Serologic analysis and quantitative and conventional reverse transcription PCR confirmed the presence of Rift Valley fever virus. The viruses belonged to lineage C, which is prevalent among Rift Valley fever viruses in southern Africa.

Rift Valley Fever Outbreak in Livestock, Mozambique, 2014

PubMed Central

Coetzee, Peter; Mubemba, Benjamin; Nhambirre, Ofélia; Neves, Luis; Coetzer, J.A.W.; Venter, Estelle H.

2016-01-01

In early 2014, abortions and death of ruminants were reported on farms in Maputo and Gaza Provinces, Mozambique. Serologic analysis and quantitative and conventional reverse transcription PCR confirmed the presence of Rift Valley fever virus. The viruses belonged to lineage C, which is prevalent among Rift Valley fever viruses in southern Africa. PMID:27869589

77 FR 68783 - Prospective Grant of Co-Exclusive License: Veterinary Vaccines for Rift Valley Fever Virus

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-16

... Grant of Co-Exclusive License: Veterinary Vaccines for Rift Valley Fever Virus AGENCY: Centers for... veterinary vaccines, to practice the inventions listed in the patent applications referred to below to... generation of precisely defined attenuated vaccine constructs that contain complete deletions of critical...

Protein Phosphatase-1 regulates Rift Valley fever virus replication.

PubMed

Baer, Alan; Shafagati, Nazly; Benedict, Ashwini; Ammosova, Tatiana; Ivanov, Andrey; Hakami, Ramin M; Terasaki, Kaori; Makino, Shinji; Nekhai, Sergei; Kehn-Hall, Kylene

2016-03-01

Rift Valley fever virus (RVFV), genus Phlebovirus family Bunyaviridae, is an arthropod-borne virus endemic throughout sub-Saharan Africa. Recent outbreaks have resulted in cyclic epidemics with an increasing geographic footprint, devastating both livestock and human populations. Despite being recognized as an emerging threat, relatively little is known about the virulence mechanisms and host interactions of RVFV. To date there are no FDA approved therapeutics or vaccines for RVF and there is an urgent need for their development. The Ser/Thr protein phosphatase 1 (PP1) has previously been shown to play a significant role in the replication of several viruses. Here we demonstrate for the first time that PP1 plays a prominent role in RVFV replication early on during the viral life cycle. Both siRNA knockdown of PP1α and a novel PP1-targeting small molecule compound 1E7-03, resulted in decreased viral titers across several cell lines. Deregulation of PP1 was found to inhibit viral RNA production, potentially through the disruption of viral RNA transcript/protein interactions, and indicates a potential link between PP1α and the viral L polymerase and nucleoprotein. These results indicate that PP1 activity is important for RVFV replication early on during the viral life cycle and may prove an attractive therapeutic target. Copyright © 2016 Elsevier B.V. All rights reserved.

Characterization of Rift Valley Fever Virus MP-12 Strain Encoding NSs of Punta Toro Virus or Sandfly Fever Sicilian Virus

PubMed Central

Lihoradova, Olga A.; Indran, Sabarish V.; Kalveram, Birte; Lokugamage, Nandadeva; Head, Jennifer A.; Gong, Bin; Tigabu, Bersabeh; Juelich, Terry L.; Freiberg, Alexander N.; Ikegami, Tetsuro

2013-01-01

Rift Valley fever virus (RVFV; genus Phlebovirus, family Bunyaviridae) is a mosquito-borne zoonotic pathogen which can cause hemorrhagic fever, neurological disorders or blindness in humans, and a high rate of abortion in ruminants. MP-12 strain, a live-attenuated candidate vaccine, is attenuated in the M- and L-segments, but the S-segment retains the virulent phenotype. MP-12 was manufactured as an Investigational New Drug vaccine by using MRC-5 cells and encodes a functional NSs gene, the major virulence factor of RVFV which 1) induces a shutoff of the host transcription, 2) inhibits interferon (IFN)-β promoter activation, and 3) promotes the degradation of dsRNA-dependent protein kinase (PKR). MP-12 lacks a marker for differentiation of infected from vaccinated animals (DIVA). Although MP-12 lacking NSs works for DIVA, it does not replicate efficiently in type-I IFN-competent MRC-5 cells, while the use of type-I IFN-incompetent cells may negatively affect its genetic stability. To generate modified MP-12 vaccine candidates encoding a DIVA marker, while still replicating efficiently in MRC-5 cells, we generated recombinant MP-12 encoding Punta Toro virus Adames strain NSs (rMP12-PTNSs) or Sandfly fever Sicilian virus NSs (rMP12-SFSNSs) in place of MP-12 NSs. We have demonstrated that those recombinant MP-12 viruses inhibit IFN-β mRNA synthesis, yet do not promote the degradation of PKR. The rMP12-PTNSs, but not rMP12-SFSNSs, replicated more efficiently than recombinant MP-12 lacking NSs in MRC-5 cells. Mice vaccinated with rMP12-PTNSs or rMP12-SFSNSs induced neutralizing antibodies at a level equivalent to those vaccinated with MP-12, and were efficiently protected from wild-type RVFV challenge. The rMP12-PTNSs and rMP12-SFSNSs did not induce antibodies cross-reactive to anti-RVFV NSs antibody and are therefore applicable to DIVA. Thus, rMP12-PTNSs is highly efficacious, replicates efficiently in MRC-5 cells, and encodes a DIVA marker, all of which are

Characterization of Rift Valley fever virus MP-12 strain encoding NSs of Punta Toro virus or sandfly fever Sicilian virus.

PubMed

Lihoradova, Olga A; Indran, Sabarish V; Kalveram, Birte; Lokugamage, Nandadeva; Head, Jennifer A; Gong, Bin; Tigabu, Bersabeh; Juelich, Terry L; Freiberg, Alexander N; Ikegami, Tetsuro

2013-01-01

Rift Valley fever virus (RVFV; genus Phlebovirus, family Bunyaviridae) is a mosquito-borne zoonotic pathogen which can cause hemorrhagic fever, neurological disorders or blindness in humans, and a high rate of abortion in ruminants. MP-12 strain, a live-attenuated candidate vaccine, is attenuated in the M- and L-segments, but the S-segment retains the virulent phenotype. MP-12 was manufactured as an Investigational New Drug vaccine by using MRC-5 cells and encodes a functional NSs gene, the major virulence factor of RVFV which 1) induces a shutoff of the host transcription, 2) inhibits interferon (IFN)-β promoter activation, and 3) promotes the degradation of dsRNA-dependent protein kinase (PKR). MP-12 lacks a marker for differentiation of infected from vaccinated animals (DIVA). Although MP-12 lacking NSs works for DIVA, it does not replicate efficiently in type-I IFN-competent MRC-5 cells, while the use of type-I IFN-incompetent cells may negatively affect its genetic stability. To generate modified MP-12 vaccine candidates encoding a DIVA marker, while still replicating efficiently in MRC-5 cells, we generated recombinant MP-12 encoding Punta Toro virus Adames strain NSs (rMP12-PTNSs) or Sandfly fever Sicilian virus NSs (rMP12-SFSNSs) in place of MP-12 NSs. We have demonstrated that those recombinant MP-12 viruses inhibit IFN-β mRNA synthesis, yet do not promote the degradation of PKR. The rMP12-PTNSs, but not rMP12-SFSNSs, replicated more efficiently than recombinant MP-12 lacking NSs in MRC-5 cells. Mice vaccinated with rMP12-PTNSs or rMP12-SFSNSs induced neutralizing antibodies at a level equivalent to those vaccinated with MP-12, and were efficiently protected from wild-type RVFV challenge. The rMP12-PTNSs and rMP12-SFSNSs did not induce antibodies cross-reactive to anti-RVFV NSs antibody and are therefore applicable to DIVA. Thus, rMP12-PTNSs is highly efficacious, replicates efficiently in MRC-5 cells, and encodes a DIVA marker, all of which are

Rift Valley Fever Virus Growth Curve Kinetics in Cattle and Sheep Peripheral Blood Monocyte Derived Macrophages

USDA-ARS?s Scientific Manuscript database

Rift Valley fever virus (RVFV), is a mosquito-borne, zoonotic pathogen within genus Phlebovirus, family Bunyaviridae that typically causes outbreaks in sub-Saharan Africa and recently spread to the Arabian Peninsula. In ruminants, RVFV infections cause mass abortion and high mortality rates in neona...

Arabidopsis thaliana plants expressing Rift Valley fever virus antigens: Mice exhibit systemic immune responses as the result of oral administration of the transgenic plants.

PubMed

Kalbina, Irina; Lagerqvist, Nina; Moiane, Bélisario; Ahlm, Clas; Andersson, Sören; Strid, Åke; Falk, Kerstin I

2016-11-01

The zoonotic Rift Valley fever virus affects livestock and humans in Africa and on the Arabian Peninsula. The economic impact of this pathogen due to livestock losses, as well as its relevance to public health, underscores the importance of developing effective and easily distributed vaccines. Vaccines that can be delivered orally are of particular interest. Here, we report the expression in transformed plants (Arabidopsis thaliana) of Rift Valley fever virus antigens. The antigens used in this study were the N protein and a deletion mutant of the Gn glycoprotein. Transformed lines were analysed for specific mRNA and protein content by RT-PCR and Western blotting, respectively. Furthermore, the plant-expressed antigens were evaluated for their immunogenicity in mice fed the transgenic plants. After oral intake of fresh transgenic plant material, a proportion of the mice elicited specific IgG antibody responses, as compared to the control animals that were fed wild-type plants and of which none sero-converted. Thus, we show that transgenic plants can be readily used to express and produce Rift Valley Fever virus proteins, and that the plants are immunogenic when given orally to mice. These are promising findings and provide a basis for further studies on edible plant vaccines against the Rift Valley fever virus. Copyright © 2016 Elsevier Inc. All rights reserved.

Potential for Psorophora columbiae and Psorophora ciliata mosquitoes (Diptera: Culicidae) to transmit Rift Valley fever virus

USDA-ARS?s Scientific Manuscript database

Rift Valley fever virus (RVFV) continues to pose a threat to much of the world. Unlike many arboviruses, numerous mosquito species have been associated with RVFV in nature, and many species have been demonstrated as competent vectors in the laboratory. In this study, we evaluated two field-collect...

A novel highly sensitive, rapid and safe Rift Valley fever virus neutralization test.

PubMed

Wichgers Schreur, Paul J; Paweska, Janusz T; Kant, Jet; Kortekaas, Jeroen

2017-10-01

Antibodies specific for Rift Valley fever virus (RVFV) can be detected by diverse methods, including ezyme-linked immunosortbent assay (ELISA) and virus neutralization test (VNT). The VNT is superior in sensitivity and specificity and is therefore considered the gold standard serological assay. Classical VNTs make use of virulent RVFV and therefore have to be performed in biosafety level 3 laboratories. Here, we report the development of a novel VNT that is based on an avirulent RVFV expressing the enhanced green fluorescent protein (eGFP), which can be performed safely outside level 3 biocontainment facilities. Evaluation with a broad panel of experimental sera and field sera demonstrated that this novel VNT is faster and more sensitive than the classical VNT. Copyright © 2017 Elsevier B.V. All rights reserved.

Interim Report on SNP analysis and forensic microarray probe design for South American hemorrhagic fever viruses, tick-borne encephalitis virus, henipaviruses, Old World Arenaviruses, filoviruses, Crimean-Congo hemorrhagic fever viruses, Rift Valley fever

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jaing, C; Gardner, S

The goal of this project is to develop forensic genotyping assays for select agent viruses, enhancing the current capabilities for the viral bioforensics and law enforcement community. We used a multipronged approach combining bioinformatics analysis, PCR-enriched samples, microarrays and TaqMan assays to develop high resolution and cost effective genotyping methods for strain level forensic discrimination of viruses. We have leveraged substantial experience and efficiency gained through year 1 on software development, SNP discovery, TaqMan signature design and phylogenetic signature mapping to scale up the development of forensics signatures in year 2. In this report, we have summarized the whole genomemore » wide SNP analysis and microarray probe design for forensics characterization of South American hemorrhagic fever viruses, tick-borne encephalitis viruses and henipaviruses, Old World Arenaviruses, filoviruses, Crimean-Congo hemorrhagic fever virus, Rift Valley fever virus and Japanese encephalitis virus.« less

Development of real-time RT-PCR for the detection of low concentrations of Rift Valley fever virus.

PubMed

Maquart, Marianne; Temmam, Sarah; Héraud, Jean-Michel; Leparc-Goffart, Isabelle; Cêtre-Sossah, Catherine; Dellagi, Koussay; Cardinale, Eric; Pascalis, Hervé

2014-01-01

In recent years, Madagascar and the Comoros archipelago have been affected by epidemics of Rift Valley fever (RVF), however detection of Rift Valley fever virus (RVFV) in zebu, sheep and goats during the post epidemic periods was frequently unsuccessful. Thus, a highly sensitive real-time RT-PCR assay was developed for the detection of RVFV at low viral loads. A new RVF SYBR Green RT-PCR targeting the M segment was tested on serum from different RVF seronegative ruminant species collected from May 2010 to August 2011 in Madagascar and the Comoros archipelago and compared with a RVF specific quantitative real time RT-PCR technique, which is considered as the reference technique. The specificity was tested on a wide range of arboviruses or other viruses giving RVF similar clinical signs. A total of 38 out of 2756 serum samples tested positive with the new RT-PCR, whereas the reference technique only detected 5 out of the 2756. The described RT-PCR is an efficient diagnostic tool for the investigation of enzootic circulation of the RVF virus. It allows the detection of low viral RNA loads adapted for the investigations of reservoirs or specific epidemiological situations such as inter-epizootic periods. Copyright © 2013 Elsevier B.V. All rights reserved.

Rift Valley fever virus NS{sub S} gene expression correlates with a defect in nuclear mRNA export

DOE Office of Scientific and Technical Information (OSTI.GOV)

Copeland, Anna Maria; Van Deusen, Nicole M.; Schmaljohn, Connie S., E-mail: Connie.s.schmaljohn.civ@mail.mil

We investigated the localization of host mRNA during Rift Valley fever virus (RVFV) infection. Fluorescence in situ hybridization revealed that infection with RVFV altered the localization of host mRNA. mRNA accumulated in the nuclei of RVFV-infected but not mock-infected cells. Further, overexpression of the NS{sub S} gene, but not the N, G{sub N} or NS{sub M} genes correlated with mRNA nuclear accumulation. Nuclear accumulation of host mRNA was not observed in cells infected with a strain of RVFV lacking the gene encoding NS{sub S}, confirming that expression of NS{sub S} is likely responsible for this phenomenon. - Highlights: • Riftmore » Valley fever virus (RVFV) infection alters the localization of host mRNA. • mRNA accumulates in the nuclei of RVFV-infected but not mock-infected cells. • NS{sub S} is likely responsible for mRNA relocalization to the nucleus.« less

Molecular detection of Rift Valley fever virus in serum samples from selected areas of Tanzania.

PubMed

Chengula, Augustino Alfred; Kasanga, Christopher Jacob; Mdegela, Robinson Hammerthon; Sallu, Raphael; Yongolo, Mmeta

2014-04-01

Rift Valley fever (RVF) is an acute mosquito-borne viral zoonotic disease affecting domestic animals and humans caused by the Rift Valley fever virus (RVFV). The virus belongs to the genus Phlebovirus of the family Bunyaviridae. The main aim of this study was to detect the presence of antibodies to RVFV as well as the virus in the serum samples that were collected from livestock during the 2006/2007 RVF outbreaks in different locations in Tanzania. Analysis of selected samples was done using a RVF-specific inhibition enzyme-linked immunosorbent assay (I-ELISA) and reverse transcription polymerase chain reaction (RT-PCR). Genomic viral RNA was extracted directly from serum samples using a QIAamp Viral RNA Mini Kit (QIAGEN), and a one-step RT-PCR protocol was used to amplify the S segment of RVFV. Positive results were obtained in 39.5% (n = 200) samples using the RVF I-ELISA, and 17.6% (n = 108) of samples were positive by RT-PCR. I-ELISA detected 41 (38.7%), 32 (39.0%), and 6 (50.0%) positive results in cattle, goats, and sheep sera, respectively, whereas the RT-PCR detected 11 (0.2%), 7 (0.2%), and 1 (0.1%) positive results in cattle, goats, and sheep sera, respectively. These findings have demonstrated the presence of RVFV in Tanzania during the 2006/2007 RVF outbreaks. To our knowledge, this is the first report to detect RVFV in serum samples from domestic animals in Tanzania using PCR technique. Therefore, a detailed molecular study to characterize the virus from different geographical locations in order to establish the profile of strains circulating in the country and develop more effective and efficient control strategies should be done.

Serologic evidence of exposure to Rift Valley fever virus detected in Tunisia

PubMed Central

Bosworth, A.; Ghabbari, T.; Dowall, S.; Varghese, A.; Fares, W.; Hewson, R.; Zhioua, E.; Chakroun, M.; Tiouiri, H.; Ben Jemaa, M.; Znazen, A.; Letaief, A.

2015-01-01

Rift Valley fever virus (RVFv) is capable of causing dramatic outbreaks amongst economically important animal species and is capable of causing severe symptoms and mortality in humans. RVFv is known to circulate widely throughout East Africa; serologic evidence of exposure has also been found in some northern African countries, including Mauritania. This study aimed to ascertain whether RVFv is circulating in regions beyond its known geographic range. Samples from febrile patients (n = 181) and nonfebrile healthy agricultural and slaughterhouse workers (n = 38) were collected during the summer of 2014 and surveyed for exposure to RVFv by both serologic tests and PCR. Of the 219 samples tested, 7.8% of nonfebrile participants showed immunoglobulin G reactivity to RVFv nucleoprotein and 8.3% of febrile patients showed immunoglobulin M reactivity, with the latter samples indicating recent exposure to the virus. Our results suggest an active circulation of RVFv and evidence of human exposure in the population of Tunisia. PMID:26740887

Rift Valley fever virus structural and non-structural proteins: Recombinant protein expression and immunoreactivity against antisera from sheep

USDA-ARS?s Scientific Manuscript database

The Rift Valley fever virus (RVFV) encodes structural proteins, nucleoprotein (N), N-terminus glycoprotein (Gn), C-terminus glycoprotein (Gc) and L protein, 78-kDa and non-structural proteins NSm and NSs. Using the baculovirus system we expressed the full-length coding sequence of N, NSs, NSm, Gc an...

Creation of Rift Valley Fever Viruses with Four-Segmented Genomes Reveals Flexibility in Bunyavirus Genome Packaging

PubMed Central

Oreshkova, Nadia; Moormann, Rob J. M.; Kortekaas, Jeroen

2014-01-01

ABSTRACT Bunyavirus genomes comprise a small (S), a medium (M), and a large (L) RNA segment of negative polarity. Although the untranslated regions have been shown to comprise signals required for transcription, replication, and encapsidation, the mechanisms that drive the packaging of at least one S, M, and L segment into a single virion to generate infectious virus are largely unknown. One of the most important members of the Bunyaviridae family that causes devastating disease in ruminants and occasionally humans is the Rift Valley fever virus (RVFV). We studied the flexibility of RVFV genome packaging by splitting the glycoprotein precursor gene, encoding the (NSm)GnGc polyprotein, into two individual genes encoding either (NSm)Gn or Gc. Using reverse genetics, six viruses with a segmented glycoprotein precursor gene were rescued, varying from a virus comprising two S-type segments in the absence of an M-type segment to a virus consisting of four segments (RVFV-4s), of which three are M-type. Despite that all virus variants were able to grow in mammalian cell lines, they were unable to spread efficiently in cells of mosquito origin. Moreover, in vivo studies demonstrated that RVFV-4s is unable to cause disseminated infection and disease in mice, even in the presence of the main virulence factor NSs, but induced a protective immune response against a lethal challenge with wild-type virus. In summary, splitting bunyavirus glycoprotein precursor genes provides new opportunities to study bunyavirus genome packaging and offers new methods to develop next-generation live-attenuated bunyavirus vaccines. IMPORTANCE Rift Valley fever virus (RVFV) causes devastating disease in ruminants and occasionally humans. Virions capable of productive infection comprise at least one copy of the small (S), medium (M), and large (L) RNA genome segments. The M segment encodes a glycoprotein precursor (GPC) protein that is cotranslationally cleaved into Gn and Gc, which are required for

Creation of Rift Valley fever viruses with four-segmented genomes reveals flexibility in bunyavirus genome packaging.

PubMed

Wichgers Schreur, Paul J; Oreshkova, Nadia; Moormann, Rob J M; Kortekaas, Jeroen

2014-09-01

Bunyavirus genomes comprise a small (S), a medium (M), and a large (L) RNA segment of negative polarity. Although the untranslated regions have been shown to comprise signals required for transcription, replication, and encapsidation, the mechanisms that drive the packaging of at least one S, M, and L segment into a single virion to generate infectious virus are largely unknown. One of the most important members of the Bunyaviridae family that causes devastating disease in ruminants and occasionally humans is the Rift Valley fever virus (RVFV). We studied the flexibility of RVFV genome packaging by splitting the glycoprotein precursor gene, encoding the (NSm)GnGc polyprotein, into two individual genes encoding either (NSm)Gn or Gc. Using reverse genetics, six viruses with a segmented glycoprotein precursor gene were rescued, varying from a virus comprising two S-type segments in the absence of an M-type segment to a virus consisting of four segments (RVFV-4s), of which three are M-type. Despite that all virus variants were able to grow in mammalian cell lines, they were unable to spread efficiently in cells of mosquito origin. Moreover, in vivo studies demonstrated that RVFV-4s is unable to cause disseminated infection and disease in mice, even in the presence of the main virulence factor NSs, but induced a protective immune response against a lethal challenge with wild-type virus. In summary, splitting bunyavirus glycoprotein precursor genes provides new opportunities to study bunyavirus genome packaging and offers new methods to develop next-generation live-attenuated bunyavirus vaccines. Rift Valley fever virus (RVFV) causes devastating disease in ruminants and occasionally humans. Virions capable of productive infection comprise at least one copy of the small (S), medium (M), and large (L) RNA genome segments. The M segment encodes a glycoprotein precursor (GPC) protein that is cotranslationally cleaved into Gn and Gc, which are required for virus entry and

Prevalence of antibodies against Rift Valley fever virus in Kenyan wildlife

PubMed Central

EVANS, A.; GAKUYA, F.; PAWESKA, J. T.; ROSTAL, M.; AKOOLO, L.; VAN VUREN, P. J.; MANYIBE, T.; MACHARIA, J. M.; KSIAZEK, T. G.; FEIKIN, D. R.; BREIMAN, R. F.; KARIUKI NJENGA, M.

2008-01-01

SUMMARY Rift Valley fever virus (RVFV) is an arbovirus associated with periodic outbreaks, mostly on the African continent, of febrile disease accompanied by abortion in livestock, and a severe, fatal haemorrhagic syndrome in humans. However, the maintenance of the virus during the inter-epidemic period (IEP) when there is low or no disease activity detected in livestock or humans has not been determined. This study report prevalence of RVFV-neutralizing antibodies in sera (n=896) collected from 16 Kenyan wildlife species including at least 35% that were born during the 1999–2006 IEP. Specimens from seven species had detectable neutralizing antibodies against RVFV, including African buffalo, black rhino, lesser kudu, impala, African elephant, kongoni, and waterbuck. High RVFV antibody prevalence (>15%) was observed in black rhinos and ruminants (kudu, impala, buffalo, and waterbuck) with the highest titres (up to 1:1280) observed mostly in buffalo, including animals born during the IEP. All lions, giraffes, plains zebras, and warthogs tested were either negative or less than two animals in each species had low (⩽1:16) titres of RVFV antibodies. Of 249 sera collected from five wildlife species during the 2006–2007 outbreak, 16 out of 19 (84%) of the ruminant (gerenuk, waterbuck, and eland) specimens had RVFV-neutralizing titres ⩾1:80. These data provide evidence that wild ruminants are infected by RVFV but further studies are required to determine whether these animals play a role in the virus maintenance between outbreaks and virus amplification prior to a noticeable outbreak. PMID:17988425

Rapamycin modulation of p70 S6 kinase signaling inhibits Rift Valley fever virus pathogenesis.

PubMed

Bell, Todd M; Espina, Virginia; Senina, Svetlana; Woodson, Caitlin; Brahms, Ashwini; Carey, Brian; Lin, Shih-Chao; Lundberg, Lindsay; Pinkham, Chelsea; Baer, Alan; Mueller, Claudius; Chlipala, Elizabeth A; Sharman, Faye; de la Fuente, Cynthia; Liotta, Lance; Kehn-Hall, Kylene

2017-07-01

Despite over 60 years of research on antiviral drugs, very few are FDA approved to treat acute viral infections. Rift Valley fever virus (RVFV), an arthropod borne virus that causes hemorrhagic fever in severe cases, currently lacks effective treatments. Existing as obligate intracellular parasites, viruses have evolved to manipulate host cell signaling pathways to meet their replication needs. Specifically, translation modulation is often necessary for viruses to establish infection in their host. Here we demonstrated phosphorylation of p70 S6 kinase, S6 ribosomal protein, and eIF4G following RVFV infection in vitro through western blot analysis and in a mouse model of infection through reverse phase protein microarrays (RPPA). Inhibition of p70 S6 kinase through rapamycin treatment reduced viral titers in vitro and increased survival and mitigated clinical disease in RVFV challenged mice. Additionally, the phosphorylation of p70 S6 kinase was decreased following rapamycin treatment in vivo. Collectively these data demonstrate modulating p70 S6 kinase can be an effective antiviral strategy. Copyright © 2017 Elsevier B.V. All rights reserved.

Four-segmented Rift Valley fever virus-based vaccines can be applied safely in ewes during pregnancy.

PubMed

Wichgers Schreur, Paul J; van Keulen, Lucien; Kant, Jet; Kortekaas, Jeroen

2017-05-25

Rift Valley fever virus (RVFV) causes severe and recurrent outbreaks on the African continent and the Arabian Peninsula and continues to expand its habitat. This mosquito-borne virus, belonging to the genus Phlebovirus of the family Bunyaviridae contains a tri-segmented negative-strand RNA genome. Previously, we developed four-segmented RVFV (RVFV-4s) variants by splitting the M-genome segment into two M-type segments each encoding one of the structural glycoproteins; Gn or Gc. Vaccination/challenge experiments with mice and lambs subsequently showed that RVFV-4s induces protective immunity against wild-type virus infection after a single administration. To demonstrate the unprecedented safety of RVFV-4s, we here report that the virus does not cause encephalitis after intranasal inoculation of mice. A study with pregnant ewes subsequently revealed that RVFV-4s does not cause viremia and does not cross the ovine placental barrier, as evidenced by the absence of teratogenic effects and virus in the blood and organs of the fetuses. Altogether, these results show that the RVFV-4s vaccine virus can be applied safely in pregnant ewes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Co-housing of Rift Valley Fever Virus Infected Lambs with Immunocompetent or Immunosuppressed Lambs Does Not Result in Virus Transmission

PubMed Central

Wichgers Schreur, Paul J.; van Keulen, Lucien; Kant, Jet; Oreshkova, Nadia; Moormann, Rob J. M.; Kortekaas, Jeroen

2016-01-01

Rift Valley fever virus (RVFV) is transmitted among susceptible animals by mosquito vectors. Although the virus can be isolated from nasal and oral swabs of infected animals and is known to be highly infectious when administered experimentally via oral or respiratory route, horizontal transmission of the virus is only sporadically reported in literature. We considered that immunosuppression resulting from stressful conditions in the field may increase the susceptibility to horizontally transmitted RVFV. Additionally, we reasoned that horizontal transmission may induce immune responses that could affect the susceptibility of contact-exposed animals to subsequent infection via mosquito vectors. To address these two hypotheses, viremic lambs were brought into contact with sentinel lambs. One group of sentinel lambs was treated with the immunosuppressive synthetic glucocorticosteroid dexamethasone and monitored for signs of disease and presence of virus in the blood and target organs. Another group of contact-exposed sentinel lambs remained untreated for three weeks and was subsequently challenged with RVFV. We found that none of the dexamethasone-treated contact-exposed lambs developed detectable viremia, antibody responses or significant increases in cytokine mRNA levels. Susceptibility of immunocompetent lambs to RVFV infection was not influenced by previous contact-exposure. Our results are discussed in light of previous findings. PMID:27014211

Mixing of M Segment DNA Vaccines to Hantaan Virus and Puumala Virus Reduces Their Immunogenicity in Hamsters

DTIC Science & Technology

2008-01-01

vaccines for Rift Valley fever virus, tick- borne encephalitis virus, Hantaan virus, and Crimean Congo hemorrhagic fever virus. Vaccine 2006;24(May 22 (21)):4657–66. ...Valley fever virus, tick-borne encephalitis virus, TNV, and Crimean Congo hemorrhagic fever virus [19]. Thus, it s clearly possible to develop certain...online 25 April 2008 eywords: a b s t r a c t To determine if DNA vaccines for two hantaviruses causing hemorrhagic

Inactivation of infectious virus and serological detection of virus antigen in Rift Valley fever virus-exposed mosquitoes fixed with paraformaldehyde.

PubMed

Kading, Rebekah; Crabtree, Mary; Miller, Barry

2013-04-01

Formaldehyde is routinely used to fix tissues in preparation for pathology studies, however concerns remain that treatment of tissues with cellular fixatives may not entirely inactivate infectious virus particles. This concern is of particular regulatory importance for research involving viruses that are classified as select agents such as Rift Valley fever virus (RVFV). Therefore, the specific aims of this study were to (1) assay RVFV-exposed Aedes aegypti mosquitoes fixed in 4% paraformaldehyde for the presence of infectious RVFV particles at various time points following infection and (2) demonstrate the utility of immunofluorescence assay (IFA) for the detection of RVFV antigen in various tissues of paraformaldehyde-fixed mosquitoes. Mosquitoes were administered an infectious blood meal containing one of two strains of RVFV, harvested at various time points following infection, intrathoracically inoculated with 4% paraformaldehyde, and fixed overnight at 4°C. The infection status of a subset of mosquitoes was verified by IFA on leg tissues prior to fixation, and infectivity of RVFV in fixed mosquito carcasses was determined by Vero cell plaque assay. Paraformaldehyde-fixed mosquitoes harvested 14 days post infection were also paraffin-embedded and sectioned for detection of RVFV antigen to particular tissues by IFA. None of the RVFV-exposed mosquitoes tested by Vero cell plaque assay contained infectious RVFV after fixation. Furthermore, incubation of mosquito sections with trypsin prior to antibody staining is recommended for optimal visualization of RVFV antigen in infected mosquito tissues by IFA. Published by Elsevier B.V.

Comparison of Rift Valley fever virus and MP-12 replication in domestic livestock and North American wildlife cell lines.

USDA-ARS?s Scientific Manuscript database

Rift Valley fever virus (RVFV) is a mosquito-transmitted pathogen that primarily affects livestock, but can also cause mild to fatal disease in humans. Currently, there is no approved vaccine for use in the United States if it were introduced. Domestic goats, sheep and cattle are susceptible hosts ...

The Pathogenesis of Rift Valley Fever

PubMed Central

Ikegami, Tetsuro; Makino, Shinji

2011-01-01

Rift Valley fever (RVF) is an emerging zoonotic disease distributed in sub-Saharan African countries and the Arabian Peninsula. The disease is caused by the Rift Valley fever virus (RVFV) of the family Bunyaviridae and the genus Phlebovirus. The virus is transmitted by mosquitoes, and virus replication in domestic ruminant results in high rates of mortality and abortion. RVFV infection in humans usually causes a self-limiting, acute and febrile illness; however, a small number of cases progress to neurological disorders, partial or complete blindness, hemorrhagic fever, or thrombosis. This review describes the pathology of RVF in human patients and several animal models, and summarizes the role of viral virulence factors and host factors that affect RVFV pathogenesis. PMID:21666766

A Spatial Analysis of Rift Valley Fever Virus Seropositivity in Domestic Ruminants in Tanzania

PubMed Central

Sindato, Calvin; Pfeiffer, Dirk U.; Karimuribo, Esron D.; Mboera, Leonard E. G.; Rweyemamu, Mark M.; Paweska, Janusz T.

2015-01-01

Rift Valley fever (RVF) is an acute arthropod-borne viral zoonotic disease primarily occurring in Africa. Since RVF-like disease was reported in Tanzania in 1930, outbreaks of the disease have been reported mainly from the eastern ecosystem of the Great Rift Valley. This cross-sectional study was carried out to describe the variation in RVF virus (RVFV) seropositivity in domestic ruminants between selected villages in the eastern and western Rift Valley ecosystems in Tanzania, and identify potential risk factors. Three study villages were purposively selected from each of the two Rift Valley ecosystems. Serum samples from randomly selected domestic ruminants (n = 1,435) were tested for the presence of specific immunoglobulin G (IgG) and M (IgM), using RVF enzyme-linked immunosorbent assay methods. Mixed effects logistic regression modelling was used to investigate the association between potential risk factors and RVFV seropositivity. The overall RVFV seroprevalence (n = 1,435) in domestic ruminants was 25.8% and speciesspecific seroprevalence was 29.7%, 27.7% and 22.0% in sheep (n = 148), cattle (n = 756) and goats (n = 531), respectively. The odds of seropositivity were significantly higher in animals sampled from the villages in the eastern than those in the western Rift Valley ecosystem (OR = 1.88, CI: 1.41, 2.51; p<0.001), in animals sampled from villages with soils of good than those with soils of poor water holding capacity (OR = 1.97; 95% CI: 1.58, 3.02; p< 0.001), and in animals which had been introduced than in animals born within the herd (OR = 5.08, CI: 2.74, 9.44; p< 0.001). Compared with animals aged 1–2 years, those aged 3 and 4–5 years had 3.40 (CI: 2.49, 4.64; p< 0.001) and 3.31 (CI: 2.27, 4.82, p< 0.001) times the odds of seropositivity. The findings confirm exposure to RVFV in all the study villages, but with a higher prevalence in the study villages from the eastern Rift Valley ecosystem. PMID:26162089

A Spatial Analysis of Rift Valley Fever Virus Seropositivity in Domestic Ruminants in Tanzania.

PubMed

Sindato, Calvin; Pfeiffer, Dirk U; Karimuribo, Esron D; Mboera, Leonard E G; Rweyemamu, Mark M; Paweska, Janusz T

2015-01-01

Rift Valley fever (RVF) is an acute arthropod-borne viral zoonotic disease primarily occurring in Africa. Since RVF-like disease was reported in Tanzania in 1930, outbreaks of the disease have been reported mainly from the eastern ecosystem of the Great Rift Valley. This cross-sectional study was carried out to describe the variation in RVF virus (RVFV) seropositivity in domestic ruminants between selected villages in the eastern and western Rift Valley ecosystems in Tanzania, and identify potential risk factors. Three study villages were purposively selected from each of the two Rift Valley ecosystems. Serum samples from randomly selected domestic ruminants (n = 1,435) were tested for the presence of specific immunoglobulin G (IgG) and M (IgM), using RVF enzyme-linked immunosorbent assay methods. Mixed effects logistic regression modelling was used to investigate the association between potential risk factors and RVFV seropositivity. The overall RVFV seroprevalence (n = 1,435) in domestic ruminants was 25.8% and species specific seroprevalence was 29.7%, 27.7% and 22.0% in sheep (n = 148), cattle (n = 756) and goats (n = 531), respectively. The odds of seropositivity were significantly higher in animals sampled from the villages in the eastern than those in the western Rift Valley ecosystem (OR = 1.88, CI: 1.41, 2.51; p<0.001), in animals sampled from villages with soils of good than those with soils of poor water holding capacity (OR = 1.97; 95% CI: 1.58, 3.02; p< 0.001), and in animals which had been introduced than in animals born within the herd (OR = 5.08, CI: 2.74, 9.44; p< 0.001). Compared with animals aged 1-2 years, those aged 3 and 4-5 years had 3.40 (CI: 2.49, 4.64; p< 0.001) and 3.31 (CI: 2.27, 4.82, p< 0.001) times the odds of seropositivity. The findings confirm exposure to RVFV in all the study villages, but with a higher prevalence in the study villages from the eastern Rift Valley ecosystem.

Serological surveillance studies confirm the Rift Valley fever virus free status in South Korea.

PubMed

Kim, Hyun Joo; Park, Jee-Yong; Jeoung, Hye-Young; Yeh, Jung-Yong; Cho, Yun-Sang; Choi, Jeong-Soo; Lee, Ji-Youn; Cho, In-Soo; Yoo, Han-Sang

2015-10-01

Rift Valley fever is a mosquito-borne zoonotic disease of domestic ruminants. This disease causes abortions in pregnant animals, and it has a high mortality rate in newborn animals. Recently, a Rift Valley fever virus (RVFV) outbreak in the Arabian Peninsula increased its potential spread to new regions worldwide. In non-endemic or disease-free countries, early detection and surveillance are important for preventing the introduction of RVFV. In this study, a serological surveillance was conducted to detect antibodies against RVFV. A total of 2382 serum samples from goats and cattle were randomly collected from nine areas in South Korea from 2011 to 2013. These samples were tested for antibodies against RVFV, using commercial ELISA kits. None of the goats and cattle were positive for antibodies against RVFV. This finding suggests that this disease is not present in South Korea, and furthermore presents the evidence of the RVFV-free status of this country.

Development and evaluation of one-step rRT-PCR and immunohistochemical methods for detection of Rift Valley fever virus in biosafety level 2 diagnostic laboratories

USDA-ARS?s Scientific Manuscript database

Rift Valley fever virus (RVFV) is a zoonotic insect transmitted virus endemic to Africa and the Arabian Peninsula. Infection causes abortions and high mortality in newborn ruminants with an overall human infection rate of <1%. The potential of RVFV as a bioterrorism agent and/or being accidentally i...

Infection and Transmission of Rift Valley Fever Viruses Lacking the NSs and/or NSm Genes in Mosquitoes: Potential Role for NSm in Mosquito Infection

PubMed Central

Crabtree, Mary B.; Kent Crockett, Rebekah J.; Bird, Brian H.; Nichol, Stuart T.; Erickson, Bobbie Rae; Biggerstaff, Brad J.; Horiuchi, Kalanthe; Miller, Barry R.

2012-01-01

Background Rift Valley fever virus is an arthropod-borne human and animal pathogen responsible for large outbreaks of acute and febrile illness throughout Africa and the Arabian Peninsula. Reverse genetics technology has been used to develop deletion mutants of the virus that lack the NSs and/or NSm virulence genes and have been shown to be stable, immunogenic and protective against Rift Valley fever virus infection in animals. We assessed the potential for these deletion mutant viruses to infect and be transmitted by Aedes mosquitoes, which are the principal vectors for maintenance of the virus in nature and emergence of virus initiating disease outbreaks, and by Culex mosquitoes which are important amplification vectors. Methodology and Principal Findings Aedes aegypti and Culex quinquefasciatus mosquitoes were fed bloodmeals containing the deletion mutant viruses. Two weeks post-exposure mosquitoes were assayed for infection, dissemination, and transmission. In Ae. aegypti, infection and transmission rates of the NSs deletion virus were similar to wild type virus while dissemination rates were significantly reduced. Infection and dissemination rates for the NSm deletion virus were lower compared to wild type. Virus lacking both NSs and NSm failed to infect Ae. aegypti. In Cx. quinquefasciatus, infection rates for viruses lacking NSm or both NSs and NSm were lower than for wild type virus. Conclusions/Significance In both species, deletion of NSm or both NSs and NSm reduced the infection and transmission potential of the virus. Deletion of both NSs and NSm resulted in the highest level of attenuation of virus replication. Deletion of NSm alone was sufficient to nearly abolish infection in Aedes aegypti mosquitoes, indicating an important role for this protein. The double deleted viruses represent an ideal vaccine profile in terms of environmental containment due to lack of ability to efficiently infect and be transmitted by mosquitoes. PMID:22563517

Infection and transmission of Rift Valley fever viruses lacking the NSs and/or NSm genes in mosquitoes: potential role for NSm in mosquito infection.

PubMed

Crabtree, Mary B; Kent Crockett, Rebekah J; Bird, Brian H; Nichol, Stuart T; Erickson, Bobbie Rae; Biggerstaff, Brad J; Horiuchi, Kalanthe; Miller, Barry R

2012-01-01

Rift Valley fever virus is an arthropod-borne human and animal pathogen responsible for large outbreaks of acute and febrile illness throughout Africa and the Arabian Peninsula. Reverse genetics technology has been used to develop deletion mutants of the virus that lack the NSs and/or NSm virulence genes and have been shown to be stable, immunogenic and protective against Rift Valley fever virus infection in animals. We assessed the potential for these deletion mutant viruses to infect and be transmitted by Aedes mosquitoes, which are the principal vectors for maintenance of the virus in nature and emergence of virus initiating disease outbreaks, and by Culex mosquitoes which are important amplification vectors. Aedes aegypti and Culex quinquefasciatus mosquitoes were fed bloodmeals containing the deletion mutant viruses. Two weeks post-exposure mosquitoes were assayed for infection, dissemination, and transmission. In Ae. aegypti, infection and transmission rates of the NSs deletion virus were similar to wild type virus while dissemination rates were significantly reduced. Infection and dissemination rates for the NSm deletion virus were lower compared to wild type. Virus lacking both NSs and NSm failed to infect Ae. aegypti. In Cx. quinquefasciatus, infection rates for viruses lacking NSm or both NSs and NSm were lower than for wild type virus. In both species, deletion of NSm or both NSs and NSm reduced the infection and transmission potential of the virus. Deletion of both NSs and NSm resulted in the highest level of attenuation of virus replication. Deletion of NSm alone was sufficient to nearly abolish infection in Aedes aegypti mosquitoes, indicating an important role for this protein. The double deleted viruses represent an ideal vaccine profile in terms of environmental containment due to lack of ability to efficiently infect and be transmitted by mosquitoes.

Culex pipiens, an Experimental Efficient Vector of West Nile and Rift Valley Fever Viruses in the Maghreb Region

PubMed Central

Amraoui, Fadila; Krida, Ghazi; Bouattour, Ali; Rhim, Adel; Daaboub, Jabeur; Harrat, Zoubir; Boubidi, Said-Chawki; Tijane, Mhamed; Sarih, Mhammed; Failloux, Anna-Bella

2012-01-01

West Nile fever (WNF) and Rift Valley fever (RVF) are emerging diseases causing epidemics outside their natural range of distribution. West Nile virus (WNV) circulates widely and harmlessly in the old world among birds as amplifying hosts, and horses and humans as accidental dead-end hosts. Rift Valley fever virus (RVFV) re-emerges periodically in Africa causing massive outbreaks. In the Maghreb, eco-climatic and entomologic conditions are favourable for WNV and RVFV emergence. Both viruses are transmitted by mosquitoes belonging to the Culex pipiens complex. We evaluated the ability of different populations of Cx. pipiens from North Africa to transmit WNV and the avirulent RVFV Clone 13 strain. Mosquitoes collected in Algeria, Morocco, and Tunisia during the summer 2010 were experimentally infected with WNV and RVFV Clone 13 strain at titers of 107.8 and 108.5 plaque forming units/mL, respectively. Disseminated infection and transmission rates were estimated 14–21 days following the exposure to the infectious blood-meal. We show that 14 days after exposure to WNV, all mosquito st developed a high disseminated infection and were able to excrete infectious saliva. However, only 69.2% of mosquito strains developed a disseminated infection with RVFV Clone 13 strain, and among them, 77.8% were able to deliver virus through saliva. Thus, Cx. pipiens from the Maghreb are efficient experimental vectors to transmit WNV and to a lesser extent, RVFV Clone 13 strain. The epidemiologic importance of our findings should be considered in the light of other parameters related to mosquito ecology and biology. PMID:22693557

Anthrax toxin receptor 1 is the cellular receptor for Seneca Valley virus

PubMed Central

Miles, Linde A.; Burga, Laura N.; Gardner, Eric E.; Bostina, Mihnea; Poirier, John T.; Rudin, Charles M.

2017-01-01

Seneca Valley virus (SVV) is an oncolytic picornavirus with selective tropism for neuroendocrine cancers. It has shown promise as a cancer therapeutic in preclinical studies and early-phase clinical trials. Here, we have identified anthrax toxin receptor 1 (ANTXR1) as the receptor for SVV using genome-wide loss-of-function screens. ANTXR1 is necessary for permissivity in vitro and in vivo. However, robust SVV replication requires an additional innate immune defect. We found that SVV interacts directly and specifically with ANTXR1, that this interaction is required for SVV binding to permissive cells, and that ANTXR1 expression is necessary and sufficient for infection in cell lines with decreased expression of antiviral IFN genes at baseline. Finally, we identified the region of the SVV capsid that is responsible for receptor recognition using cryoelectron microscopy of the SVV-ANTXR1-Fc complex. These studies identify ANTXR1, a class of receptor that is shared by a mammalian virus and a bacterial toxin, as the cellular receptor for SVV. PMID:28650343

Vaccination of alpacas against Rift Valley fever virus: Safety, immunogenicity and pathogenicity of MP-12 vaccine.

PubMed

Rissmann, M; Ulrich, R; Schröder, C; Hammerschmidt, B; Hanke, D; Mroz, C; Groschup, M H; Eiden, M

2017-01-23

Rift Valley fever (RVF) is an emerging zoonosis of major public health concern in Africa and Arabia. Previous outbreaks attributed camelids a significant role in the epidemiology of Rift Valley fever virus (RVFV), making them an important target species for vaccination. Using three alpacas as model-organisms for dromedary camels, the safety, immunogenicity and pathogenicity of the MP-12 vaccine were evaluated in this study. To compare both acute and subacute effects, animals were euthanized at 3 and 31days post infection (dpi). Clinical monitoring, analysis of liver enzymes and hematological parameters demonstrated the tolerability of the vaccine, as no significant adverse effects were observed. Comprehensive analysis of serological parameters illustrated the immunogenicity of the vaccine, eliciting high neutralizing antibody titers and antibodies targeting different viral antigens. RVFV was detected in serum and liver of the alpaca euthanized 3dpi, whereas no virus was detectable at 31dpi. Viral replication was confirmed by detection of various RVFV-antigens in hepatocytes by immunohistochemistry and the presence of mild multifocal necrotizing hepatitis. In conclusion, results indicate that MP-12 is a promising vaccine candidate but still has a residual pathogenicity, which requires further investigation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Diagnostic approaches for Rift Valley Fever

USDA-ARS?s Scientific Manuscript database

Disease outbreaks caused by arthropod-borne animal viruses (arboviruses) resulting in significant livestock and economic losses world-wide appear to be increasing. Rift Valley fever (RVF) virus (RVFV) is an important arbovirus that causes lethal disease in cattle, camels, sheep and goats in Sub-Saha...

Crystallization and preliminary X-ray diffraction studies of Seneca Valley Virus-001, a new member of the Picornaviridae family

DOE Office of Scientific and Technical Information (OSTI.GOV)

Venkataraman, Sangita; Reddy, Seshidhar P.; Loo, Jackie

2008-04-01

Seneca Valley Virus-001 of the Picornavirdae family was crystallized in the space group R3 and X-ray diffraction data was collected to a resolution of 2.3 Å. Rotation-function studies suggested the presence of two distict sets of 20 protomers that belong to two different virus particles in the crystallographic asymmetric unit. Seneca Valley Virus-001 (SVV-001) is a newly found species in the Picornaviridae family. SVV-001 is the first naturally occurring nonpathogenic picorna@@virus observed to mediate selective cytotoxicity towards tumor cells with neuroendocrine cancer features. The nonsegmented (+)ssRNA genome of SVV-001 shares closest sequence similarity to the genomes of the members ofmore » the Cardiovirus genus. However, based on the distinct characteristics of the genome organization and other biochemical properties, it has been suggested that SVV-001 represents a new genus, namely ‘Senecavirus’, in the Picornaviridae family. In order to understand the oncolytic properties of SVV-001, the native virus was crystallized using the hanging-drop vapour-diffusion method. The crystals belonged to space group R3, with unit-cell parameters (in the hexagonal setting) a = b = 311.5, c = 1526.4 Å. Although the SVV crystals diffracted to better than 2.3 Å resolution, the data quality is acceptable [I/σ(I) > 2.0] to 2.6 Å resolution. The unit-cell volume and the locked rotation-function analysis suggest that six particles could be accommodated in the unit cell, with two distinct sets of one third of a particle, each containing 20 protomers, occupying the crystallographic asymmetric unit.« less

Curcumin Inhibits Rift Valley Fever Virus Replication in Human Cells*

PubMed Central

Narayanan, Aarthi; Kehn-Hall, Kylene; Senina, Svetlana; Lundberg, Lindsay; Van Duyne, Rachel; Guendel, Irene; Das, Ravi; Baer, Alan; Bethel, Laura; Turell, Michael; Hartman, Amy Lynn; Das, Bhaskar; Bailey, Charles; Kashanchi, Fatah

2012-01-01

Rift Valley fever virus (RVFV) is an arbovirus that is classified as a select agent, an emerging infectious virus, and an agricultural pathogen. Understanding RVFV-host interactions is imperative to the design of novel therapeutics. Here, we report that an infection by the MP-12 strain of RVFV induces phosphorylation of the p65 component of the NFκB cascade. We demonstrate that phosphorylation of p65 (serine 536) involves phosphorylation of IκBα and occurs through the classical NFκB cascade. A unique, low molecular weight complex of the IKK-β subunit can be observed in MP-12-infected cells, which we have labeled IKK-β2. The IKK-β2 complex retains kinase activity and phosphorylates an IκBα substrate. Inhibition of the IKK complex using inhibitors impairs viral replication, thus alluding to the requirement of an active IKK complex to the viral life cycle. Curcumin strongly down-regulates levels of extracellular infectious virus. Our data demonstrated that curcumin binds to and inhibits kinase activity of the IKK-β2 complex in infected cells. Curcumin partially exerts its inhibitory influence on RVFV replication by interfering with IKK-β2-mediated phosphorylation of the viral protein NSs and by altering the cell cycle of treated cells. Curcumin also demonstrated efficacy against ZH501, the fully virulent version of RVFV. Curcumin treatment down-regulated viral replication in the liver of infected animals. Our data point to the possibility that RVFV infection may result in the generation of novel versions of host components (such as IKK-β2) that, by virtue of altered protein interaction and function, qualify as unique therapeutic targets. PMID:22847000

Evaluation of efficacy, potential for vector transmission and duration of immunity testing of MP-12, an attenuated Rift Valley fever virus vaccine candidate, in sheep

USDA-ARS?s Scientific Manuscript database

Rift Valley fever virus (RVFV) causes serious disease in ruminants and humans in Africa. There are currently no fully licensed vaccines for this arthropod-borne virus in the US. Studies in sheep and cattle have found an attenuated strain of RVFV, MP-12, to be both safe and efficacious, and a conditi...

Update: Increase in Human Infections with Novel Asian Lineage Avian Influenza A(H7N9) Viruses During the Fifth Epidemic - China, October 1, 2016-August 7, 2017.

PubMed

Kile, James C; Ren, Ruiqi; Liu, Liqi; Greene, Carolyn M; Roguski, Katherine; Iuliano, A Danielle; Jang, Yunho; Jones, Joyce; Thor, Sharmi; Song, Ying; Zhou, Suizan; Trock, Susan C; Dugan, Vivien; Wentworth, David E; Levine, Min Z; Uyeki, Timothy M; Katz, Jacqueline M; Jernigan, Daniel B; Olsen, Sonja J; Fry, Alicia M; Azziz-Baumgartner, Eduardo; Davis, C Todd

2017-09-08

(CVV) were produced in 2013 that have been used to make vaccines against Asian H7N9 viruses circulating at that time. CDC is working with partners to enhance surveillance for Asian H7N9 viruses in humans and poultry, to improve laboratory capability to detect and characterize H7N9 viruses, and to develop, test and distribute new CVV that could be used for vaccine production if a vaccine is needed.

Rift Valley fever outbreak, southern Mauritania, 2012.

PubMed

Sow, Abdourahmane; Faye, Ousmane; Ba, Yamar; Ba, Hampathé; Diallo, Diawo; Faye, Oumar; Loucoubar, Cheikh; Boushab, Mohamed; Barry, Yahya; Diallo, Mawlouth; Sall, Amadou Alpha

2014-02-01

After a period of heavy rainfall, an outbreak of Rift Valley fever occurred in southern Mauritania during September-November 2012. A total of 41 human cases were confirmed, including 13 deaths, and 12 Rift Valley fever virus strains were isolated. Moudjeria and Temchecket Departments were the most affected areas.

Seroprevalence of Antibodies against Chikungunya, Dengue, and Rift Valley Fever Viruses after Febrile Illness Outbreak, Madagascar

PubMed Central

Girmann, Mirko; Randriamampionona, Njary; Bialonski, Alexandra; Maus, Deborah; Krefis, Anne Caroline; Njarasoa, Christine; Rajanalison, Jeanne Fleury; Ramandrisoa, Herly Daniel; Randriarison, Maurice Lucien; May, Jürgen; Schmidt-Chanasit, Jonas; Rakotozandrindrainy, Raphael

2012-01-01

In October 2009, two–3 months after an outbreak of a febrile disease with joint pain on the eastern coast of Madagascar, we assessed serologic markers for chikungunya virus (CHIKV), dengue virus (DENV), and Rift Valley fever virus (RVFV) in 1,244 pregnant women at 6 locations. In 2 eastern coast towns, IgG seroprevalence against CHIKV was 45% and 23%; IgM seroprevalence was 28% and 5%. IgG seroprevalence against DENV was 17% and 11%. No anti-DENV IgM was detected. At 4 locations, 450–1,300 m high, IgG seroprevalence against CHIKV was 0%–3%, suggesting CHIKV had not spread to higher inland-altitudes. Four women had IgG against RVFV, probably antibodies from a 2008 epidemic. Most (78%) women from coastal locations with CHIKV-specific IgG reported joint pain and stiffness; 21% reported no symptoms. CHIKV infection was significantly associated with high bodyweight. The outbreak was an isolated CHIKV epidemic without relevant DENV co-transmission. PMID:23092548

Phylogeography of Rift Valley Fever Virus in Africa Reveals Multiple Introductions in Senegal and Mauritania

PubMed Central

Faye, Ousmane; Diallo, Mawlouth; de Oliveira, Juliana Velasco C.; Zanotto, Paolo M. A.; Sall, Amadou Alpha

2012-01-01

Rift Valley Fever (RVF) virus (Family Bunyaviridae) is an arthropod-borne RNA virus that infects primarily domestic ruminants and occasionally humans. RVF epizootics are characterized by numerous abortions and mortality among young animals. In humans, the illness is usually characterized by a mild self-limited febrile illness, which could progress to more serious complications. RVF virus is widespread and endemic in many regions of Africa. In Western Africa, several outbreaks have been reported since 1987 when the first major one occurred at the frontier of Senegal and Mauritania. Aiming to evaluate the spreading and molecular epidemiology in these countries, RVFV isolates from 1944 to 2008 obtained from 18 localities in Senegal and Mauritania and 15 other countries were investigated. Our results suggest that a more intense viral activity possibly took place during the last century compared to the recent past and that at least 5 introductions of RVFV took place in Senegal and Mauritania from distant African regions. Moreover, Barkedji in Senegal was possibly a hub associated with the three distinct entries of RVFV in West Africa. PMID:22539961

Creation of a Recombinant Rift Valley Fever Virus with a Two-Segmented Genome ▿ †

PubMed Central

Brennan, Benjamin; Welch, Stephen R.; McLees, Angela; Elliott, Richard M.

2011-01-01

Rift Valley fever virus (RVFV; family Bunyaviridae) is a clinically important, mosquito-borne pathogen of both livestock and humans, which is found mainly in sub-Saharan Africa and the Arabian Peninsula. RVFV has a trisegmented single-stranded RNA (ssRNA) genome. The L and M segments are negative sense and encode the L protein (viral polymerase) on the L segment and the virion glycoproteins Gn and Gc as well as two other proteins, NSm and 78K, on the M segment. The S segment uses an ambisense coding strategy to express the nucleocapsid protein, N, and the nonstructural protein, NSs. Both the NSs and NSm proteins are dispensable for virus growth in tissue culture. Using reverse genetics, we generated a recombinant virus, designated r2segMP12, containing a two-segmented genome in which the NSs coding sequence was replaced with that for the Gn and Gc precursor. Thus, r2segMP12 lacks an M segment, and although it was attenuated in comparison to the three-segmented parental virus in both mammalian and insect cell cultures, it was genetically stable over multiple passages. We further show that the virus can stably maintain an M-like RNA segment encoding the enhanced green fluorescent protein gene. The implications of these findings for RVFV genome packaging and the potential to develop multivalent live-attenuated vaccines are discussed. PMID:21795328

Structure of the Rift Valley fever virus nucleocapsid protein reveals another architecture for RNA encapsidation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Raymond, Donald D.; Piper, Mary E.; Gerrard, Sonja R.

2010-07-13

Rift Valley fever virus (RVFV) is a negative-sense RNA virus (genus Phlebovirus, family Bunyaviridae) that infects livestock and humans and is endemic to sub-Saharan Africa. Like all negative-sense viruses, the segmented RNA genome of RVFV is encapsidated by a nucleocapsid protein (N). The 1.93-{angstrom} crystal structure of RVFV N and electron micrographs of ribonucleoprotein (RNP) reveal an encapsidated genome of substantially different organization than in other negative-sense RNA virus families. The RNP polymer, viewed in electron micrographs of both virus RNP and RNP reconstituted from purified N with a defined RNA, has an extended structure without helical symmetry. N-RNA speciesmore » of {approx}100-kDa apparent molecular weight and heterogeneous composition were obtained by exhaustive ribonuclease treatment of virus RNP, by recombinant expression of N, and by reconstitution from purified N and an RNA oligomer. RNA-free N, obtained by denaturation and refolding, has a novel all-helical fold that is compact and well ordered at both the N and C termini. Unlike N of other negative-sense RNA viruses, RVFV N has no positively charged surface cleft for RNA binding and no protruding termini or loops to stabilize a defined N-RNA oligomer or RNP helix. A potential protein interaction site was identified in a conserved hydrophobic pocket. The nonhelical appearance of phlebovirus RNP, the heterogeneous {approx}100-kDa N-RNA multimer, and the N fold differ substantially from the RNP and N of other negative-sense RNA virus families and provide valuable insights into the structure of the encapsidated phlebovirus genome.« less

Characterization of infectious Murray Valley encephalitis virus derived from a stably cloned genome-length cDNA.

PubMed

Hurrelbrink, R J; Nestorowicz, A; McMinn, P C

1999-12-01

An infectious cDNA clone of Murray Valley encephalitis virus prototype strain 1-51 (MVE-1-51) was constructed by stably inserting genome-length cDNA into the low-copy-number plasmid vector pMC18. Designated pMVE-1-51, the clone consisted of genome-length cDNA of MVE-1-51 under the control of a T7 RNA polymerase promoter. The clone was constructed by using existing components of a cDNA library, in addition to cDNA of the 3' terminus derived by RT-PCR of poly(A)-tailed viral RNA. Upon comparison with other flavivirus sequences, the previously undetermined sequence of the 3' UTR was found to contain elements conserved throughout the genus FLAVIVIRUS: RNA transcribed from pMVE-1-51 and subsequently transfected into BHK-21 cells generated infectious virus. The plaque morphology, replication kinetics and antigenic profile of clone-derived virus (CDV-1-51) was similar to the parental virus in vitro. Furthermore, the virulence properties of CDV-1-51 and MVE-1-51 (LD(50) values and mortality profiles) were found to be identical in vivo in the mouse model. Through site-directed mutagenesis, the infectious clone should serve as a valuable tool for investigating the molecular determinants of virulence in MVE virus.

Prevalence of protozoa, viruses, coliphages and indicator bacteria in groundwater and river water in the Kathmandu Valley, Nepal.

PubMed

Haramoto, Eiji; Yamada, Kaoru; Nishida, Kei

2011-12-01

Limited information is available on the prevalence of waterborne pathogens in aquatic environments in developing countries. In this study, water samples were collected from nine shallow wells and a river in the Kathmandu Valley, Nepal, during the rainy season in 2009 and were subjected to detection of waterborne protozoa, viruses and coliphages using a recently developed method for simultaneous concentration of protozoa and viruses in water. Escherichia coli and total coliforms were also tested as indicator bacteria. At least one type of the five pathogens tested (Cryptosporidium, Giardia, human adenoviruses, and noroviruses of genogroups I and II) was detected in five groundwater samples (56%) (1000 ml each) from shallow wells. Compared with groundwater samples, the pathogens were more abundant in the river water sample (100ml); the concentrations of Cryptosporidium and Giardia were 140 oocysts/l and 8500 cysts/l, respectively, and the mean threshold cycle (Ct) values in real-time RT-PCR were 34.3, 36.8 and 34.0 for human adenoviruses and noroviruses of genogroups I and II, respectively. Genotyping of F-RNA coliphages by real-time RT-PCR was successfully used to differentiate human and animal faecal contamination in the samples. Moreover, for the groundwater samples, protozoa and viruses were detected only in E. coli-positive samples, suggesting that E. coli may be an appropriate indicator of pathogen contamination of valley groundwater. Copyright © 2011 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.

Seroprevalence of Rift Valley fever virus in livestock during inter-epidemic period in Egypt, 2014/15.

PubMed

Mroz, Claudia; Gwida, Mayada; El-Ashker, Maged; El-Diasty, Mohamed; El-Beskawy, Mohamed; Ziegler, Ute; Eiden, Martin; Groschup, Martin H

2017-04-05

Rift Valley fever virus (RVFV) caused several outbreaks throughout the African continent and the Arabian Peninsula posing significant threat to human and animal health. In Egypt the first and most important Rift Valley fever epidemic occurred during 1977/78 with a multitude of infected humans and huge economic losses in livestock. After this major outbreak, RVF epidemics re-occurred in irregular intervals between 1993 and 2003. Seroprevalence of anti-RVFV antibodies in livestock during inter-epidemic periods can be used for supporting the evaluation of the present risk exposure for animal and public health. A serosurvey was conducted during 2014/2015 in non-vaccinated livestock including camels, sheep, goats and buffalos in different areas of the Nile River Delta as well as the furthermost southeast of Egypt to investigate the presence of anti-RVFV antibodies for further evaluating of the risk exposure for animal and human health. All animals integrated in this study were born after the last Egyptian RVF epidemic in 2003 and sampled buffalos and small ruminants were not imported from other endemic countries. A total of 873 serum samples from apparently healthy animals from different host species (camels: n = 221; sheep: n = 438; goats: n = 26; buffalo: n = 188) were tested serologically using RVFV competition ELISA, virus neutralization test and/or an indirect immunofluorescence assay, depending on available serum volume. Sera were assessed positive when virus neutralization test alone or least two assays produced consistent positive results. The overall seroprevalence was 2.29% (95%CI: 1.51-3.07) ranging from 0% in goats, 0.46% in sheep (95%CI: 0.41-0.5), and 3.17% in camels (95%CI: 0.86-5.48) up to 5.85% in buffalos (95%CI: 2.75-8.95). Our findings assume currently low level of circulating virus in the investigated areas and suggest minor indication for a new RVF epidemic. Further the results may indicate that during long inter-epidemic periods

Patterns of Rift Valley fever activity in Zambia.

PubMed Central

Davies, F. G.; Kilelu, E.; Linthicum, K. J.; Pegram, R. G.

1992-01-01

An hypothesis that there was an annual emergence of Rift Valley fever virus in Zambia, during or after the seasonal rains, was examined with the aid of sentinel cattle. Serum samples taken during 1974 and 1978 showed evidence of epizootic Rift Valley fever in Zambia, with more than 80% positive. A sentinel herd exposed from 1982 to 1986 showed that some Rift Valley fever occurred each year. This was usually at a low level, with 3-8% of the susceptible cattle seroconverting. In 1985-6 more than 20% of the animals seroconverted, and this greater activity was associated with vegetational changes--which could be detected by remote-sensing satellite imagery--which have also been associated with greater virus activity in Kenya. PMID:1547835

Has Rift Valley fever virus evolved with increasing severity in human populations in East Africa?

PubMed

Baba, Marycelin; Masiga, Daniel K; Sang, Rosemary; Villinger, Jandouwe

2016-06-22

Rift Valley fever (RVF) outbreaks have occurred across eastern Africa from 1912 to 2010 approximately every 4-15 years, most of which have not been accompanied by significant epidemics in human populations. However, human epidemics during RVF outbreaks in eastern Africa have involved 478 deaths in 1998, 1107 reported cases with 350 deaths from 2006 to 2007 and 1174 cases with 241 deaths in 2008. We review the history of RVF outbreaks in eastern Africa to identify the epidemiological factors that could have influenced its increasing severity in humans. Diverse ecological factors influence outbreak frequency, whereas virus evolution has a greater impact on its virulence in hosts. Several factors could have influenced the lack of information on RVF in humans during earlier outbreaks, but the explosive nature of human RVF epidemics in recent years mirrors the evolutionary trend of the virus. Comparisons between isolates from different outbreaks have revealed an accumulation of genetic mutations and genomic reassortments that have diversified RVF virus genomes over several decades. The threat to humans posed by the diversified RVF virus strains increases the potential public health and socioeconomic impacts of future outbreaks. Understanding the shifting RVF epidemiology as determined by its evolution is key to developing new strategies for outbreak mitigation and prevention of future human RVF casualties.

Observations on the epidemiology of Rift Valley fever in Kenya.

PubMed

Davies, F G

1975-10-01

The epizootic range of Rift Valley fever in Kenya is defined from the results of virus isolations during epizootics, and form an extensive serological survey of cattle which were exposed during an epizootic. A study of the sera from a wide range of wild bovidae sampled immediately after the epizootic, showed that they did not act as reservoir or amplifying hosts for RVF. Virus isolation attempts from a variety of rodents proved negative. Rift Valley fever did not persist between epizootics by producing symptomless abortions in cattle in areas within its epizootic range. A sentinel herd sampled annually after an epizootic in 1968 revealed not one single seroconversion from 1969 to 1974. Certain forest and forest edge situations were postulated as enzootic for Rift Valley fever, and a small percentage of seroconversions were detected in cattle in these areas, born four years after the last epizootic. This has been the only evidence for the persistence of the virus in Kenya since 1968, and may be a part of the interepizootic maintenance cycle for Rift Valley fever in Kenya, which otherwise remains unknown.

Combination Kinase Inhibitor Treatment Suppresses Rift Valley Fever Virus Replication.

PubMed

Bell, Todd M; Espina, Virginia; Lundberg, Lindsay; Pinkham, Chelsea; Brahms, Ashwini; Carey, Brian D; Lin, Shih-Chao; Dahal, Bibha; Woodson, Caitlin; de la Fuente, Cynthia; Liotta, Lance A; Bailey, Charles L; Kehn-Hall, Kylene

2018-04-13

Viruses must parasitize host cell translational machinery in order to make proteins for viral progeny. In this study, we sought to use this signal transduction conduit against them by inhibiting multiple kinases that influence translation. Previous work indicated that several kinases involved in translation, including p70 S6K, p90RSK, ERK, and p38 MAPK, are phosphorylated following Rift Valley fever virus (RVFV) infection. Furthermore, inhibiting p70 S6K through treatment with the FDA approved drug rapamycin prevents RVFV pathogenesis in a mouse model of infection. We hypothesized that inhibiting either p70 S6K, p90RSK, or p90RSK’s upstream kinases, ERK and p38 MAPK, would decrease translation and subsequent viral replication. Treatment with the p70 S6K inhibitor PF-4708671 resulted in decreased phosphorylation of translational proteins and reduced RVFV titers. In contrast, treatment with the p90RSK inhibitor BI-D1870, p38MAPK inhibitor SB203580, or the ERK inhibitor PD0325901 alone had minimal influence on RVFV titers. The combination of PF-4708671 and BI-D1870 treatment resulted in robust inhibition of RVFV replication. Likewise, a synergistic inhibition of RVFV replication was observed with p38MAPK inhibitor SB203580 or the ERK inhibitor PD0325901 combined with rapamycin treatment. These findings serve as a proof of concept regarding combination kinase inhibitor treatment for RVFV infection.

Combination Kinase Inhibitor Treatment Suppresses Rift Valley Fever Virus Replication

PubMed Central

Bell, Todd M.; Espina, Virginia; Lundberg, Lindsay; Pinkham, Chelsea; Brahms, Ashwini; Dahal, Bibha; Woodson, Caitlin; de la Fuente, Cynthia; Liotta, Lance A.; Bailey, Charles L.

2018-01-01

Viruses must parasitize host cell translational machinery in order to make proteins for viral progeny. In this study, we sought to use this signal transduction conduit against them by inhibiting multiple kinases that influence translation. Previous work indicated that several kinases involved in translation, including p70 S6K, p90RSK, ERK, and p38 MAPK, are phosphorylated following Rift Valley fever virus (RVFV) infection. Furthermore, inhibiting p70 S6K through treatment with the FDA approved drug rapamycin prevents RVFV pathogenesis in a mouse model of infection. We hypothesized that inhibiting either p70 S6K, p90RSK, or p90RSK’s upstream kinases, ERK and p38 MAPK, would decrease translation and subsequent viral replication. Treatment with the p70 S6K inhibitor PF-4708671 resulted in decreased phosphorylation of translational proteins and reduced RVFV titers. In contrast, treatment with the p90RSK inhibitor BI-D1870, p38MAPK inhibitor SB203580, or the ERK inhibitor PD0325901 alone had minimal influence on RVFV titers. The combination of PF-4708671 and BI-D1870 treatment resulted in robust inhibition of RVFV replication. Likewise, a synergistic inhibition of RVFV replication was observed with p38MAPK inhibitor SB203580 or the ERK inhibitor PD0325901 combined with rapamycin treatment. These findings serve as a proof of concept regarding combination kinase inhibitor treatment for RVFV infection. PMID:29652799

Transmission potential of Rift Valley fever virus over the course of the 2010 epidemic in South Africa.

PubMed

Métras, Raphaëlle; Baguelin, Marc; Edmunds, W John; Thompson, Peter N; Kemp, Alan; Pfeiffer, Dirk U; Collins, Lisa M; White, Richard G

2013-06-01

A Rift Valley fever (RVF) epidemic affecting animals on domestic livestock farms was reported in South Africa during January-August 2010. The first cases occurred after heavy rainfall, and the virus subsequently spread countrywide. To determine the possible effect of environmental conditions and vaccination on RVF virus transmissibility, we estimated the effective reproduction number (Re) for the virus over the course of the epidemic by extending the Wallinga and Teunis algorithm with spatial information. Re reached its highest value in mid-February and fell below unity around mid-March, when vaccination coverage was 7.5%-45.7% and vector-suitable environmental conditions were maintained. The epidemic fade-out likely resulted first from the immunization of animals following natural infection or vaccination. The decline in vector-suitable environmental conditions from April onwards and further vaccination helped maintain Re below unity. Increased availability of vaccine use data would enable evaluation of the effect of RVF vaccination campaigns.

Potential application of silver nanoparticles to control the infectivity of Rift Valley fever virus in vitro and in vivo.

PubMed

Borrego, Belén; Lorenzo, Gema; Mota-Morales, Josué D; Almanza-Reyes, Horacio; Mateos, Francisco; López-Gil, Elena; de la Losa, Nuria; Burmistrov, Vasily A; Pestryakov, Alexey N; Brun, Alejandro; Bogdanchikova, Nina

2016-07-01

In this work we have tested the potential antiviral activity of silver nanoparticles formulated as Argovit™ against Rift Valley fever virus (RVFV). The antiviral activity of Argovit was tested on Vero cell cultures and in type-I interferon receptor deficient mice (IFNAR (-/-) mice) by two different approaches: (i) different dilutions of Argovit were added to previously infected cells or administrated to animals infected with a lethal dose of virus; (ii) virus was pre-incubated with different dilutions of Argovit before inoculation in mice or cells. Though the ability of silver nanoparticles to control an ongoing RVFV infection in the conditions tested was limited, the incubation of virus with Argovit before the infection led to a reduction of the infectivity titers both in vitro and in vivo. These results reveal the potential application of silver nanoparticles to control the infectivity of RVFV, which is an important zoonotic pathogen. Copyright © 2016 Elsevier Inc. All rights reserved.

Multiplex detection of IgG and IgM to Rift Valley fever virus nucleoprotein, nonstructural proteins, and glycoprotein in ovine and bovine

USDA-ARS?s Scientific Manuscript database

A multiplex fluorescence microsphere immunoassay (FMIA) was used to detect bovine and ovine IgM and IgG antibodies to several Rift Valley fever virus (RVFV) proteins, including the major surface glycoprotein, Gn; the nonstructural proteins, NSs and NSm; and the nucleoprotein, N. Target antigens were...

Has Rift Valley fever virus evolved with increasing severity in human populations in East Africa?

PubMed Central

Baba, Marycelin; Masiga, Daniel K; Sang, Rosemary; Villinger, Jandouwe

2016-01-01

Rift Valley fever (RVF) outbreaks have occurred across eastern Africa from 1912 to 2010 approximately every 4–15 years, most of which have not been accompanied by significant epidemics in human populations. However, human epidemics during RVF outbreaks in eastern Africa have involved 478 deaths in 1998, 1107 reported cases with 350 deaths from 2006 to 2007 and 1174 cases with 241 deaths in 2008. We review the history of RVF outbreaks in eastern Africa to identify the epidemiological factors that could have influenced its increasing severity in humans. Diverse ecological factors influence outbreak frequency, whereas virus evolution has a greater impact on its virulence in hosts. Several factors could have influenced the lack of information on RVF in humans during earlier outbreaks, but the explosive nature of human RVF epidemics in recent years mirrors the evolutionary trend of the virus. Comparisons between isolates from different outbreaks have revealed an accumulation of genetic mutations and genomic reassortments that have diversified RVF virus genomes over several decades. The threat to humans posed by the diversified RVF virus strains increases the potential public health and socioeconomic impacts of future outbreaks. Understanding the shifting RVF epidemiology as determined by its evolution is key to developing new strategies for outbreak mitigation and prevention of future human RVF casualties. PMID:27329846

A Single Vaccination with an Improved Nonspreading Rift Valley Fever Virus Vaccine Provides Sterile Immunity in Lambs

PubMed Central

Oreshkova, Nadia; van Keulen, Lucien; Kant, Jet; Moormann, Rob J. M.; Kortekaas, Jeroen

2013-01-01

Rift Valley fever virus (RVFV) is an important pathogen that affects ruminants and humans. Recently we developed a vaccine based on nonspreading RVFV (NSR) and showed that a single vaccination with this vaccine protects lambs from viremia and clinical signs. However, low levels of viral RNA were detected in the blood of vaccinated lambs shortly after challenge infection. These low levels of virus, when present in a pregnant ewe, could potentially infect the highly susceptible fetus. We therefore aimed to further improve the efficacy of the NSR vaccine. Here we report the expression of Gn, the major immunogenic protein of the virus, from the NSR genome. The resulting NSR-Gn vaccine was shown to elicit superior CD8 and CD4-restricted memory responses and improved virus neutralization titers in mice. A dose titration study in lambs revealed that the highest vaccination dose of 106.3 TCID50/ml protected all lambs from clinical signs and viremia. The lambs developed neutralizing antibodies within three weeks after vaccination and no anamnestic responses were observed following challenge. The combined results suggest that sterile immunity was achieved by a single vaccination with the NSR-Gn vaccine. PMID:24167574

Rift valley Fever in Kruger national park: do buffalo play a role in the inter-epidemic circulation of virus?

PubMed

Beechler, B R; Bengis, R; Swanepoel, R; Paweska, J T; Kemp, A; van Vuren, P Jansen; Joubert, J; Ezenwa, V O; Jolles, A E

2015-02-01

Rift Valley fever (RVF) is a zoonotic mosquito-borne virus disease of livestock and wild ruminants that has been identified as a risk for international spread. Typically, the disease occurs in geographically limited outbreaks associated with high rainfall events and can cause massive losses of livestock. It is unclear how RVF virus persists during inter-epidemic periods but cryptic cycling of the virus in wildlife populations may play a role. We investigated the role that free-living African buffalo (Syncerus caffer caffer) might play in inter-epidemic circulation of the virus and looked for geographic, age and sex patterns of Rift Valley fever virus (RVFV) infection in African buffalo. Buffalo serum samples were collected (n = 1615) in Kruger National Park (KNP), South Africa, during a period of 1996-2007 and tested for antibodies to RVF. We found that older animals were more likely to be seropositive for anti-RVFV antibody than younger animals, but sex was not correlated with the likelihood of being anti-RVFV antibody positive. We also found geographic variation within KNP; herds in the south were more likely to have acquired anti-RVFV antibody than herds farther north - which could be driven by host or vector ecology. In all years of the study between 1996 and 2007, we found young buffalo (under 2 years of age) that were seropositive for anti-RVFV antibody, with prevalence ranging between 0 and 27% each year, indicating probable circulation. In addition, we also conducted a 4-year longitudinal study on 227 initially RVFV seronegative buffalo to look for evidence of seroconversion outside known RVF outbreaks within our study period (2008-2012). In the longitudinal study, we found five individuals that seroconverted from anti-RVFV antibody negative to anti-RVFV antibody positive, outside of any detected outbreak. Overall, our results provide evidence of long-term undetected circulation of RVFV in the buffalo population. © 2013 Blackwell Verlag GmbH.

Blood Meal Analysis of and Virus Detection in Mosquitoes Collected during a Rift Valley fever Epizootic/Epidemic: Implications for epidemic disease transmission dynamics

USDA-ARS?s Scientific Manuscript database

Rift Valley fever (RVF) is a zoonosis of domestic ruminants in Africa. Bloodfed mosquitoes collected during the 2006-2007 RVF outbreak in Kenya were analyzed to determine the virus infection status and animal source of the bloodmeals. Bloodmeals from individual mosquito abdomens were screened for v...

Complete genome analysis of 33 ecologically and biologically diverse Rift Valley fever virus strains reveals widespread virus movement and low genetic diversity due to recent common ancestry.

PubMed

Bird, Brian H; Khristova, Marina L; Rollin, Pierre E; Ksiazek, Thomas G; Nichol, Stuart T

2007-03-01

Rift Valley fever (RVF) virus is a mosquito-borne RNA virus responsible for large explosive outbreaks of acute febrile disease in humans and livestock in Africa with significant mortality and economic impact. The successful high-throughput generation of the complete genome sequence was achieved for 33 diverse RVF virus strains collected from throughout Africa and Saudi Arabia from 1944 to 2000, including strains differing in pathogenicity in disease models. While several distinct virus genetic lineages were determined, which approximately correlate with geographic origin, multiple exceptions indicative of long-distance virus movement have been found. Virus strains isolated within an epidemic (e.g., Mauritania, 1987, or Egypt, 1977 to 1978) exhibit little diversity, while those in enzootic settings (e.g., 1970s Zimbabwe) can be highly diverse. In addition, the large Saudi Arabian RVF outbreak in 2000 appears to have involved virus introduction from East Africa, based on the close ancestral relationship of a 1998 East African virus. Virus genetic diversity was low (approximately 5%) and primarily involved accumulation of mutations at an average of 2.9 x 10(-4) substitutions/site/year, although some evidence of RNA segment reassortment was found. Bayesian analysis of current RVF virus genetic diversity places the most recent common ancestor of these viruses in the late 1800s, the colonial period in Africa, a time of dramatic changes in agricultural practices and introduction of nonindigenous livestock breeds. In addition to insights into the evolution and ecology of RVF virus, these genomic data also provide a foundation for the design of molecular detection assays and prototype vaccines useful in combating this important disease.

Observations on rift valley fever virus and vaccines in Egypt

PubMed Central

2011-01-01

Rift Valley Fever virus (RVFV, genus: Phlebovirus, family: Bunyaviridae), is an arbovirus which causes significant morbidity and mortality in animals and humans. RVFV was introduced for the first time in Egypt in 1977. In endemic areas, the insect vector control and vaccination is considering appropriate measures if applied properly and the used vaccine is completely safe and the vaccination programs cover all the susceptible animals. Egypt is importing livestock and camels from the African Horn & the Sudan for human consumption. The imported livestock and camels were usually not vaccinated against RVFV. But in rare occasions, the imported livestock were vaccinated but with unknown date of vaccination and the unvaccinated control contacts were unavailable for laboratory investigations. Also, large number of the imported livestock and camels are often escaped slaughtering for breeding which led to the spread of new strains of FMD and the introduction of RVFV from the enzootic African countries. This article provide general picture about the present situation of RVFV in Egypt to help in controlling this important disease. PMID:22152149

Ultrastructural study of Rift Valley fever virus in the mouse model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reed, Christopher; Steele, Keith E.; Honko, Anna

Detailed ultrastructural studies of Rift Valley fever virus (RVFV) in the mouse model are needed to develop and characterize a small animal model of RVF for the evaluation of potential vaccines and therapeutics. In this study, the ultrastructural features of RVFV infection in the mouse model were analyzed. The main changes in the liver included the presence of viral particles in hepatocytes and hepatic stem cells accompanied by hepatocyte apoptosis. However, viral particles were observed rarely in the liver; in contrast, particles were extremely abundant in the CNS. Despite extensive lymphocytolysis, direct evidence of viral replication was not observed inmore » the lymphoid tissue. These results correlate with the acute-onset hepatitis and delayed-onset encephalitis that are dominant features of severe human RVF, but suggest that host immune-mediated mechanisms contribute significantly to pathology. The results of this study expand our knowledge of RVFV-host interactions and further characterize the mouse model of RVF.« less

Serological Evidence for the Circulation of Rift Valley Fever Virus in Domestic Small Ruminants in Southern Gabon.

PubMed

Maganga, Gael Darren; Abessolo Ndong, Andre Lea; Mikala Okouyi, Clency Sylde; Makiala Mandanda, Sheila; N'Dilimabaka, Nadine; Pinto, Anais; Agossou, Ernest; Cossic, Brieuc; Akue, Jean-Paul; Leroy, Eric Maurice

2017-06-01

Rift Valley fever (RVF) is a zoonotic disease, which caused several epidemics in humans in many countries of Africa. Using an inhibition enzyme-linked immunosorbent assay (ELISA), real-time reverse transcription PCR, and nested one-step reverse transcription PCR, we conducted a cross-sectional study in populations of sheep and goats from the Mongo County in 2014 to determine the circulation of the Rift Valley fever virus (RVFV) in small ruminants from this area. From a total of 201 small ruminants (95 sheep and 106 goats), the overall IgG seroprevalence against the RVFV was 6.47% (13/201). No RVFV RNA was detected in the animal plasmas. Logistic regression analysis showed that age, species, sex, and locality were not the significant risk factors. The findings of this study highlight the risk of RVF for domestic ruminants bred in this region and for the human rural population living in contact with these animals and they emphasize the need to develop adequate control measures to limit this threat.

Inter-epidemic Acquisition of Rift Valley Fever Virus in Humans in Tanzania

PubMed Central

Sumaye, Robert David; Abatih, Emmanuel Nji; Thiry, Etienne; Amuri, Mbaraka; Berkvens, Dirk; Geubbels, Eveline

2015-01-01

Background In East Africa, epidemics of Rift Valley fever (RVF) occur in cycles of 5–15 years following unusually high rainfall. RVF transmission during inter-epidemic periods (IEP) generally passes undetected in absence of surveillance in mammalian hosts and vectors. We studied IEP transmission of RVF and evaluated the demographic, behavioural, occupational and spatial determinants of past RVF infection. Methodology Between March and August 2012 we collected blood samples, and administered a risk factor questionnaire among 606 inhabitants of 6 villages in the seasonally inundated Kilombero Valley, Tanzania. ELISA tests were used to detect RVFV IgM and IgG antibodies in serum samples. Risk factors were examined by mixed effects logistic regression. Findings RVF virus IgM antibodies, indicating recent RVFV acquisition, were detected in 16 participants, representing 2.6% overall and in 22.5% of inhibition ELISA positives (n = 71). Four of 16 (25.0%) IgM positives and 11/71 (15.5%) of individuals with inhibition ELISA sero-positivity reported they had had no previous contact with host animals. Sero-positivity on inhibition ELISA was 11.7% (95% CI 9.2–14.5) and risk was elevated with age (odds ratio (OR) 1.03 per year; 95% CI 1.01–1.04), among milkers (OR 2.19; 95% CI 1.23–3.91), and individuals eating raw meat (OR 4.17; 95% CI 1.18–14.66). Households keeping livestock had a higher probability of having members with evidence of past infection (OR = 3.04, 95% CI = 1.42–6.48) than those that do not keep livestock. Conclusion There is inter-epidemic acquisition of RVFV in Kilombero Valley inhabitants. In the wake of declining malaria incidence, these findings underscore the need for clinicians to consider RVF in the differential diagnosis for febrile illnesses. Several types of direct contact with livestock are important risk factors for past infection with RVFV in this study’s population. However, at least part of RVFV transmission appears to have occurred

Rift Valley fever virus NSS gene expression correlates with a defect in nuclear mRNA export.

PubMed

Copeland, Anna Maria; Van Deusen, Nicole M; Schmaljohn, Connie S

2015-12-01

We investigated the localization of host mRNA during Rift Valley fever virus (RVFV) infection. Fluorescence in situ hybridization revealed that infection with RVFV altered the localization of host mRNA. mRNA accumulated in the nuclei of RVFV-infected but not mock-infected cells. Further, overexpression of the NSS gene, but not the N, GN or NSM genes correlated with mRNA nuclear accumulation. Nuclear accumulation of host mRNA was not observed in cells infected with a strain of RVFV lacking the gene encoding NSS, confirming that expression of NSS is likely responsible for this phenomenon. Published by Elsevier Inc.

Rift Valley fever virus NSs protein functions and the similarity to other bunyavirus NSs proteins.

PubMed

Ly, Hoai J; Ikegami, Tetsuro

2016-07-02

Rift Valley fever is a mosquito-borne zoonotic disease that affects both ruminants and humans. The nonstructural (NS) protein, which is a major virulence factor for Rift Valley fever virus (RVFV), is encoded on the S-segment. Through the cullin 1-Skp1-Fbox E3 ligase complex, the NSs protein promotes the degradation of at least two host proteins, the TFIIH p62 and the PKR proteins. NSs protein bridges the Fbox protein with subsequent substrates, and facilitates the transfer of ubiquitin. The SAP30-YY1 complex also bridges the NSs protein with chromatin DNA, affecting cohesion and segregation of chromatin DNA as well as the activation of interferon-β promoter. The presence of NSs filaments in the nucleus induces DNA damage responses and causes cell-cycle arrest, p53 activation, and apoptosis. Despite the fact that NSs proteins have poor amino acid similarity among bunyaviruses, the strategy utilized to hijack host cells are similar. This review will provide and summarize an update of recent findings pertaining to the biological functions of the NSs protein of RVFV as well as the differences from those of other bunyaviruses.

Rift Valley fever.

PubMed

Paweska, J T

2015-08-01

Rift Valley fever (RVF) is a mosquito-borne zoonotic viral disease affecting domestic and wild ruminants, camels and humans. The causative agent of RVF, the RVF virus (RVFV), has the capacity to cause large and severe outbreaks in animal and human populations and to cross significant natural geographic barriers. Rift Valley fever is usually inapparent in non-pregnant adult animals, but pregnant animals and newborns can be severely affected; outbreaks are characterised by a sudden onset of abortions and high neonatal mortality. The majority of human infections are subclinical or associated with moderate to severe, non-fatal, febrile illness, but some patients may develop a haemorrhagic syndrome and/or ocular and neurological lesions. In both animals and humans, the primary site of RVFV replication and tissue pathology is the liver. Outbreaks of RVF are associated with persistent high rainfalls leading to massive flooding and the emergence of large numbers of competent mosquito vectors that transmit the virus to a wide range of susceptible vertebrate species. Outbreaks of RVF have devastating economic effects on countries for which animal trade constitutes the main source of national revenue. The propensity of the virus to spread into new territories and re-emerge in traditionally endemic regions, where it causes large outbreaks in human and animal populations, presents a formidable challenge for public and veterinary health authorities. The presence of competent mosquito vectors in RVF-free countries, the wide range of mammals susceptible to the virus, altering land use, the global changes in climate, and increased animal trade and travel are some of the factors which might contribute to international spread of RVF.

Innate Immune Response to Rift Valley Fever Virus in Goats

PubMed Central

Nfon, Charles K.; Marszal, Peter; Zhang, Shunzhen; Weingartl, Hana M.

2012-01-01

Rift Valley fever (RVF), a re-emerging mosquito-borne disease of ruminants and man, was endemic in Africa but spread to Saudi Arabia and Yemen, meaning it could spread even further. Little is known about innate and cell-mediated immunity to RVF virus (RVFV) in ruminants, which is knowledge required for adequate vaccine trials. We therefore studied these aspects in experimentally infected goats. We also compared RVFV grown in an insect cell-line and that grown in a mammalian cell-line for differences in the course of infection. Goats developed viremia one day post infection (DPI), which lasted three to four days and some goats had transient fever coinciding with peak viremia. Up to 4% of peripheral blood mononuclear cells (PBMCs) were positive for RVFV. Monocytes and dendritic cells in PBMCs declined possibly from being directly infected with virus as suggested by in vitro exposure. Infected goats produced serum IFN-γ, IL-12 and other proinflammatory cytokines but not IFN-α. Despite the lack of IFN-α, innate immunity via the IL-12 to IFN-γ circuit possibly contributed to early protection against RVFV since neutralising antibodies were detected after viremia had cleared. The course of infection with insect cell-derived RVFV (IN-RVFV) appeared to be different from mammalian cell-derived RVFV (MAM-RVFV), with the former attaining peak viremia faster, inducing fever and profoundly affecting specific immune cell subpopulations. This indicated possible differences in infections of ruminants acquired from mosquito bites relative to those due to contact with infectious material from other animals. These differences need to be considered when testing RVF vaccines in laboratory settings. PMID:22545170

Innate immune response to Rift Valley fever virus in goats.

PubMed

Nfon, Charles K; Marszal, Peter; Zhang, Shunzhen; Weingartl, Hana M

2012-01-01

Rift Valley fever (RVF), a re-emerging mosquito-borne disease of ruminants and man, was endemic in Africa but spread to Saudi Arabia and Yemen, meaning it could spread even further. Little is known about innate and cell-mediated immunity to RVF virus (RVFV) in ruminants, which is knowledge required for adequate vaccine trials. We therefore studied these aspects in experimentally infected goats. We also compared RVFV grown in an insect cell-line and that grown in a mammalian cell-line for differences in the course of infection. Goats developed viremia one day post infection (DPI), which lasted three to four days and some goats had transient fever coinciding with peak viremia. Up to 4% of peripheral blood mononuclear cells (PBMCs) were positive for RVFV. Monocytes and dendritic cells in PBMCs declined possibly from being directly infected with virus as suggested by in vitro exposure. Infected goats produced serum IFN-γ, IL-12 and other proinflammatory cytokines but not IFN-α. Despite the lack of IFN-α, innate immunity via the IL-12 to IFN-γ circuit possibly contributed to early protection against RVFV since neutralising antibodies were detected after viremia had cleared. The course of infection with insect cell-derived RVFV (IN-RVFV) appeared to be different from mammalian cell-derived RVFV (MAM-RVFV), with the former attaining peak viremia faster, inducing fever and profoundly affecting specific immune cell subpopulations. This indicated possible differences in infections of ruminants acquired from mosquito bites relative to those due to contact with infectious material from other animals. These differences need to be considered when testing RVF vaccines in laboratory settings.

A Review of Mosquitoes Associated with Rift Valley Fever Virus in Madagascar

PubMed Central

Tantely, Luciano M.; Boyer, Sébastien; Fontenille, Didier

2015-01-01

Rift Valley fever (RVF) is a viral zoonotic disease occurring throughout Africa, the Arabian Peninsula, and Madagascar. The disease is caused by a Phlebovirus (RVF virus [RVFV]) transmitted to vertebrate hosts through the bite of infected mosquitoes. In Madagascar, the first RVFV circulation was reported in 1979 based on detection in mosquitoes but without epidemic episode. Subsequently, two outbreaks occurred: the first along the east coast and in the central highlands in 1990 and 1991 and the most recent along the northern and eastern coasts and in the central highlands in 2008 and 2009. Despite the presence of 24 mosquitoes species potentially associated with RVFV transmission in Madagascar, little associated entomological information is available. In this review, we list the RVFV vector, Culex antennatus, as well as other taxa as candidate vector species. We discuss risk factors from an entomological perspective for the re-emergence of RVF in Madagascar. PMID:25732680

Towards a better understanding of Rift Valley fever epidemiology in the south-west of the Indian Ocean

PubMed Central

2013-01-01

Rift Valley fever virus (Phlebovirus, Bunyaviridae) is an arbovirus causing intermittent epizootics and sporadic epidemics primarily in East Africa. Infection causes severe and often fatal illness in young sheep, goats and cattle. Domestic animals and humans can be contaminated by close contact with infectious tissues or through mosquito infectious bites. Rift Valley fever virus was historically restricted to sub-Saharan countries. The probability of Rift Valley fever emerging in virgin areas is likely to be increasing. Its geographical range has extended over the past years. As a recent example, autochthonous cases of Rift Valley fever were recorded in 2007–2008 in Mayotte in the Indian Ocean. It has been proposed that a single infected animal that enters a naive country is sufficient to initiate a major outbreak before Rift Valley fever virus would ever be detected. Unless vaccines are available and widely used to limit its expansion, Rift Valley fever will continue to be a critical issue for human and animal health in the region of the Indian Ocean. PMID:24016237

Towards a better understanding of Rift Valley fever epidemiology in the south-west of the Indian Ocean.

PubMed

Balenghien, Thomas; Cardinale, Eric; Chevalier, Véronique; Elissa, Nohal; Failloux, Anna-Bella; Jean Jose Nipomichene, Thiery Nirina; Nicolas, Gaelle; Rakotoharinome, Vincent Michel; Roger, Matthieu; Zumbo, Betty

2013-09-09

Rift Valley fever virus (Phlebovirus, Bunyaviridae) is an arbovirus causing intermittent epizootics and sporadic epidemics primarily in East Africa. Infection causes severe and often fatal illness in young sheep, goats and cattle. Domestic animals and humans can be contaminated by close contact with infectious tissues or through mosquito infectious bites. Rift Valley fever virus was historically restricted to sub-Saharan countries. The probability of Rift Valley fever emerging in virgin areas is likely to be increasing. Its geographical range has extended over the past years. As a recent example, autochthonous cases of Rift Valley fever were recorded in 2007-2008 in Mayotte in the Indian Ocean. It has been proposed that a single infected animal that enters a naive country is sufficient to initiate a major outbreak before Rift Valley fever virus would ever be detected. Unless vaccines are available and widely used to limit its expansion, Rift Valley fever will continue to be a critical issue for human and animal health in the region of the Indian Ocean.

Seroepidemiological Survey of Rift Valley Fever Virus in Ruminants in Garissa, Kenya.

PubMed

Nanyingi, Mark O; Muchemi, Gerald M; Thumbi, Samuel M; Ade, Fredrick; Onyango, Clayton O; Kiama, Stephen G; Bett, Bernard

2017-02-01

Rift Valley fever (RVF) is a vector-borne zoonotic disease caused by phlebovirus in the family Bunyaviridae. In Kenya, major outbreaks occurred in 1997-1998 and 2006-2007 leading to human deaths, huge economic losses because of livestock morbidity, mortality, and restrictions on livestock trade. This study was conducted to determine RVF seroprevalence in cattle, sheep, and goats during an interepidemic period in Garissa County in Kenya. In July 2013, we performed a cross-sectional survey and sampled 370 ruminants from eight RVF-prone areas of Garissa County. Rift Valley fever virus (RVFV) antibodies were detected using a multispecies competitive enzyme-linked immunosorbent assay. Mixed effect logistic regression models were used to determine the association between RVF seropositivity and species, sex, age, and location of the animals. A total of 271 goats, 87 sheep, and 12 cattle were sampled and the overall immunoglobulin G seroprevalence was 27.6% (95% CI [23-32.1]). Sheep, cattle, and goats had seroprevalences of 32.2% (95% CI [20.6-31]), 33.3% (95% CI [6.7-60]), and 25.8% (95% CI [22.4-42]), respectively. Seropositivity in males was 31.8% (95% CI [22.2-31.8]), whereas that of females was 27% (95% CI [18.1-45.6]). The high seroprevalence suggests RVFV circulation in domestic ruminants in Garissa and may be indicative of a subclinal infection. These findings provide evidence of RVF disease status that will assist decision-makers to flag areas of high risk of RVF outbreaks and prioritize the implementation of timely and cost-effective vaccination programs.

High-Throughput Screening Using a Whole-Cell Virus Replication Reporter Gene Assay to Identify Inhibitory Compounds against Rift Valley Fever Virus Infection.

PubMed

Islam, Md Koushikul; Baudin, Maria; Eriksson, Jonas; Öberg, Christopher; Habjan, Matthias; Weber, Friedemann; Överby, Anna K; Ahlm, Clas; Evander, Magnus

2016-04-01

Rift Valley fever virus (RVFV) is an emerging virus that causes serious illness in humans and livestock. There are no approved vaccines or treatments for humans. The purpose of the study was to identify inhibitory compounds of RVFV infection without any preconceived idea of the mechanism of action. A whole-cell-based high-throughput drug screening assay was developed to screen 28,437 small chemical compounds targeting RVFV infection. To accomplish both speed and robustness, a replication-competent NSs-deleted RVFV expressing a fluorescent reporter gene was developed. Inhibition of fluorescence intensity was quantified by spectrophotometry and related to virus infection in human lung epithelial cells (A549). Cell toxicity was assessed by the Resazurin cell viability assay. After primary screening, 641 compounds were identified that inhibited RVFV infection by ≥80%, with ≥50% cell viability at 50 µM concentration. These compounds were subjected to a second screening regarding dose-response profiles, and 63 compounds with ≥60% inhibition of RVFV infection at 3.12 µM compound concentration and ≥50% cell viability at 25 µM were considered hits. Of these, six compounds with high inhibitory activity were identified. In conclusion, the high-throughput assay could efficiently and safely identify several promising compounds that inhibited RVFV infection. © 2016 Society for Laboratory Automation and Screening.

Four-segmented Rift Valley fever virus induces sterile immunity in sheep after a single vaccination.

PubMed

Wichgers Schreur, Paul J; Kant, Jet; van Keulen, Lucien; Moormann, Rob J M; Kortekaas, Jeroen

2015-03-17

Rift Valley fever virus (RVFV), a mosquito-borne virus in the Bunyaviridae family, causes recurrent outbreaks with severe disease in ruminants and occasionally humans. The virus comprises a segmented genome consisting of a small (S), medium (M) and large (L) RNA segment of negative polarity. The M-segment encodes a glycoprotein precursor (GPC) protein that is co-translationally cleaved into Gn and Gc, which are required for virus entry and fusion. Recently we developed a four-segmented RVFV (RVFV-4s) by splitting the M-genome segment, and used this virus to study RVFV genome packaging. Here we evaluated the potential of a RVFV-4s variant lacking the NSs gene (4s-ΔNSs) to induce protective immunity in sheep. Groups of seven lambs were either mock-vaccinated or vaccinated with 10(5) or 10(6) tissue culture infective dose (TCID50) of 4s-ΔNSs via the intramuscular (IM) or subcutaneous (SC) route. Three weeks post-vaccination all lambs were challenged with wild-type RVFV. Mock-vaccinated lambs developed high fever and high viremia within 2 days post-challenge and three animals eventually succumbed to the infection. In contrast, none of the 4s-ΔNSs vaccinated animals developed clinical signs during the course of the experiment. Vaccination with 10(5) TCID50 via the IM route provided sterile immunity, whereas a 10(6) dose was required to induce sterile immunity via SC vaccination. Protection was strongly correlated with the presence of RVFV neutralizing antibodies. This study shows that 4s-ΔNSs is able to induce sterile immunity in the natural target species after a single vaccination, preferably administrated via the IM route. Copyright © 2015 Elsevier Ltd. All rights reserved.

Rift Valley Fever Virus Epidemic in Kenya, 2006/2007: The Entomologic Investigations

PubMed Central

Sang, Rosemary; Kioko, Elizabeth; Lutomiah, Joel; Warigia, Marion; Ochieng, Caroline; O'Guinn, Monica; Lee, John S.; Koka, Hellen; Godsey, Marvin; Hoel, David; Hanafi, Hanafi; Miller, Barry; Schnabel, David; Breiman, Robert F.; Richardson, Jason

2010-01-01

In December 2006, Rift Valley fever (RVF) was diagnosed in humans in Garissa Hospital, Kenya and an outbreak reported affecting 11 districts. Entomologic surveillance was performed in four districts to determine the epidemic/epizootic vectors of RVF virus (RVFV). Approximately 297,000 mosquitoes were collected, 164,626 identified to species, 72,058 sorted into 3,003 pools and tested for RVFV by reverse transcription-polymerase chain reaction. Seventy-seven pools representing 10 species tested positive for RVFV, including Aedes mcintoshi/circumluteolus (26 pools), Aedes ochraceus (23 pools), Mansonia uniformis (15 pools); Culex poicilipes, Culex bitaeniorhynchus (3 pools each); Anopheles squamosus, Mansonia africana (2 pools each); Culex quinquefasciatus, Culex univittatus, Aedes pembaensis (1 pool each). Positive Ae. pembaensis, Cx. univittatus, and Cx. bitaeniorhynchus was a first time observation. Species composition, densities, and infection varied among districts supporting hypothesis that different mosquito species serve as epizootic/epidemic vectors of RVFV in diverse ecologies, creating a complex epidemiologic pattern in East Africa. PMID:20682903

A review of mosquitoes associated with Rift Valley fever virus in Madagascar.

PubMed

Tantely, Luciano M; Boyer, Sébastien; Fontenille, Didier

2015-04-01

Rift Valley fever (RVF) is a viral zoonotic disease occurring throughout Africa, the Arabian Peninsula, and Madagascar. The disease is caused by a Phlebovirus (RVF virus [RVFV]) transmitted to vertebrate hosts through the bite of infected mosquitoes. In Madagascar, the first RVFV circulation was reported in 1979 based on detection in mosquitoes but without epidemic episode. Subsequently, two outbreaks occurred: the first along the east coast and in the central highlands in 1990 and 1991 and the most recent along the northern and eastern coasts and in the central highlands in 2008 and 2009. Despite the presence of 24 mosquitoes species potentially associated with RVFV transmission in Madagascar, little associated entomological information is available. In this review, we list the RVFV vector, Culex antennatus, as well as other taxa as candidate vector species. We discuss risk factors from an entomological perspective for the re-emergence of RVF in Madagascar. © The American Society of Tropical Medicine and Hygiene.

Rift Valley fever virus epidemic in Kenya, 2006/2007: the entomologic investigations.

PubMed

Sang, Rosemary; Kioko, Elizabeth; Lutomiah, Joel; Warigia, Marion; Ochieng, Caroline; O'Guinn, Monica; Lee, John S; Koka, Hellen; Godsey, Marvin; Hoel, David; Hanafi, Hanafi; Miller, Barry; Schnabel, David; Breiman, Robert F; Richardson, Jason

2010-08-01

In December 2006, Rift Valley fever (RVF) was diagnosed in humans in Garissa Hospital, Kenya and an outbreak reported affecting 11 districts. Entomologic surveillance was performed in four districts to determine the epidemic/epizootic vectors of RVF virus (RVFV). Approximately 297,000 mosquitoes were collected, 164,626 identified to species, 72,058 sorted into 3,003 pools and tested for RVFV by reverse transcription-polymerase chain reaction. Seventy-seven pools representing 10 species tested positive for RVFV, including Aedes mcintoshi/circumluteolus (26 pools), Aedes ochraceus (23 pools), Mansonia uniformis (15 pools); Culex poicilipes, Culex bitaeniorhynchus (3 pools each); Anopheles squamosus, Mansonia africana (2 pools each); Culex quinquefasciatus, Culex univittatus, Aedes pembaensis (1 pool each). Positive Ae. pembaensis, Cx. univittatus, and Cx. bitaeniorhynchus was a first time observation. Species composition, densities, and infection varied among districts supporting hypothesis that different mosquito species serve as epizootic/epidemic vectors of RVFV in diverse ecologies, creating a complex epidemiologic pattern in East Africa.

NSs protein of severe fever with thrombocytopenia syndrome virus suppresses interferon production through different mechanism than Rift Valley fever virus.

PubMed

Zhang, S; Zheng, B; Wang, T; Li, A; Wan, J; Qu, J; Li, C H; Li, D; Liang, M

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a newly identified Phlebovirus that causes severe fever with thrombocytopenia syndrome. Our study demonstrated that SFTSV NSs functioned as IFN antagonist mainly by suppressing TBK1/IKKε-IRF3 signaling pathway. NSs interacted with and relocalized TANK-binding kinase 1 (TBK1) into NSs-induced cytoplasmic structures and this interaction could effectively inhibit downstream phosphorylation and dimerization of interferon regulatory factor 3 (IRF3), resulting in the suppression of antiviral signaling and IFN induction. Functional sites of SFTSV NSs binding with TBK1 were then studied and results showed that NSs had lost their IFN-inhibiting activity after deleting the 25 amino acids in N-terminal. Furthermore, the mechanism of Rift Valley fever virus (RVFV) NSs blocking IFN-β response were also investigated. Preliminary results showed that RVFV NSs proteins could neither interact nor co-localize with TBK1 in cytoplasm, but suppressed its expression levels, phosphorylation and dimerization of IRF3 in the subsequent steps, resulting in inhibition of the IFN-β production. Altogether, our data demonstrated the probable mechanism used by SFTSV to inhibit IFN responses which was different from RVFV and pointed toward a novel mechanism for RVFV suppressing IFN responses.

Attenuation of pathogenic Rift Valley fever virus strain through the chimeric S-segment encoding sandfly fever phlebovirus NSs or a dominant-negative PKR

PubMed Central

Nishiyama, Shoko; Slack, Olga A. L.; Lokugamage, Nandadeva; Hill, Terence E.; Juelich, Terry L.; Zhang, Lihong; Smith, Jennifer K.; Perez, David; Gong, Bin; Freiberg, Alexander N.; Ikegami, Tetsuro

2016-01-01

ABSTRACT Rift Valley fever is a mosquito-borne zoonotic disease affecting ruminants and humans. Rift Valley fever virus (RVFV: family Bunyaviridae, genus Phlebovirus) causes abortions and fetal malformations in ruminants, and hemorrhagic fever, encephalitis, or retinitis in humans. The live-attenuated MP-12 vaccine is conditionally licensed for veterinary use in the US. However, this vaccine lacks a marker for the differentiation of vaccinated from infected animals (DIVA). NSs gene is dispensable for RVFV replication, and thus, rMP-12 strains lacking NSs gene is applicable to monitor vaccinated animals. However, the immunogenicity of MP-12 lacking NSs was not as high as parental MP-12. Thus, chimeric MP-12 strains encoding NSs from either Toscana virus (TOSV), sandfly fever Sicilian virus (SFSV) or Punta Toro virus Adames strain (PTA) were characterized previously. Although chimeric MP-12 strains are highly immunogenic, the attenuation through the S-segment remains unknown. Using pathogenic ZH501 strain, we aimed to demonstrate the attenuation of ZH501 strain through chimeric S-segment encoding either the NSs of TOSV, SFSV, PTA, or Punta Toro virus Balliet strain (PTB). In addition, we characterized rZH501 encoding a human dominant-negative PKR (PKRΔE7), which also enhances the immunogenicity of MP-12. Study done on mice revealed that attenuation of rZH501 occurred through the S-segment encoding either PKRΔE7 or SFSV NSs. However, rZH501 encoding either TOSV, PTA, or PTB NSs in the S-segment uniformly caused lethal encephalitis. Our results indicated that the S-segments encoding PKRΔE7 or SFSV NSs are attenuated and thus applicable toward next generation MP-12 vaccine candidates that encode a DIVA marker. PMID:27248570

Attenuation of pathogenic Rift Valley fever virus strain through the chimeric S-segment encoding sandfly fever phlebovirus NSs or a dominant-negative PKR.

PubMed

Nishiyama, Shoko; Slack, Olga A L; Lokugamage, Nandadeva; Hill, Terence E; Juelich, Terry L; Zhang, Lihong; Smith, Jennifer K; Perez, David; Gong, Bin; Freiberg, Alexander N; Ikegami, Tetsuro

2016-11-16

Rift Valley fever is a mosquito-borne zoonotic disease affecting ruminants and humans. Rift Valley fever virus (RVFV: family Bunyaviridae, genus Phlebovirus) causes abortions and fetal malformations in ruminants, and hemorrhagic fever, encephalitis, or retinitis in humans. The live-attenuated MP-12 vaccine is conditionally licensed for veterinary use in the US. However, this vaccine lacks a marker for the differentiation of vaccinated from infected animals (DIVA). NSs gene is dispensable for RVFV replication, and thus, rMP-12 strains lacking NSs gene is applicable to monitor vaccinated animals. However, the immunogenicity of MP-12 lacking NSs was not as high as parental MP-12. Thus, chimeric MP-12 strains encoding NSs from either Toscana virus (TOSV), sandfly fever Sicilian virus (SFSV) or Punta Toro virus Adames strain (PTA) were characterized previously. Although chimeric MP-12 strains are highly immunogenic, the attenuation through the S-segment remains unknown. Using pathogenic ZH501 strain, we aimed to demonstrate the attenuation of ZH501 strain through chimeric S-segment encoding either the NSs of TOSV, SFSV, PTA, or Punta Toro virus Balliet strain (PTB). In addition, we characterized rZH501 encoding a human dominant-negative PKR (PKRΔE7), which also enhances the immunogenicity of MP-12. Study done on mice revealed that attenuation of rZH501 occurred through the S-segment encoding either PKRΔE7 or SFSV NSs. However, rZH501 encoding either TOSV, PTA, or PTB NSs in the S-segment uniformly caused lethal encephalitis. Our results indicated that the S-segments encoding PKRΔE7 or SFSV NSs are attenuated and thus applicable toward next generation MP-12 vaccine candidates that encode a DIVA marker.

Single-Molecule FISH Reveals Non-selective Packaging of Rift Valley Fever Virus Genome Segments

PubMed Central

Wichgers Schreur, Paul J.; Kortekaas, Jeroen

2016-01-01

The bunyavirus genome comprises a small (S), medium (M), and large (L) RNA segment of negative polarity. Although genome segmentation confers evolutionary advantages by enabling genome reassortment events with related viruses, genome segmentation also complicates genome replication and packaging. Accumulating evidence suggests that genomes of viruses with eight or more genome segments are incorporated into virions by highly selective processes. Remarkably, little is known about the genome packaging process of the tri-segmented bunyaviruses. Here, we evaluated, by single-molecule RNA fluorescence in situ hybridization (FISH), the intracellular spatio-temporal distribution and replication kinetics of the Rift Valley fever virus (RVFV) genome and determined the segment composition of mature virions. The results reveal that the RVFV genome segments start to replicate near the site of infection before spreading and replicating throughout the cytoplasm followed by translocation to the virion assembly site at the Golgi network. Despite the average intracellular S, M and L genome segments approached a 1:1:1 ratio, major differences in genome segment ratios were observed among cells. We also observed a significant amount of cells lacking evidence of M-segment replication. Analysis of two-segmented replicons and four-segmented viruses subsequently confirmed the previous notion that Golgi recruitment is mediated by the Gn glycoprotein. The absence of colocalization of the different segments in the cytoplasm and the successful rescue of a tri-segmented variant with a codon shuffled M-segment suggested that inter-segment interactions are unlikely to drive the copackaging of the different segments into a single virion. The latter was confirmed by direct visualization of RNPs inside mature virions which showed that the majority of virions lack one or more genome segments. Altogether, this study suggests that RVFV genome packaging is a non-selective process. PMID:27548280

Transmission of Rift Valley fever virus from European-breed lambs to Culex pipiens mosquitoes.

PubMed

Vloet, Rianka P M; Vogels, Chantal B F; Koenraadt, Constantianus J M; Pijlman, Gorben P; Eiden, Martin; Gonzales, Jose L; van Keulen, Lucien J M; Wichgers Schreur, Paul J; Kortekaas, Jeroen

2017-12-01

Rift Valley fever virus (RVFV) is a mosquito-borne bunyavirus of the genus Phlebovirus that is highly pathogenic to ruminants and humans. The disease is currently confined to Africa and the Arabian Peninsula, but globalization and climate change may facilitate introductions of the virus into currently unaffected areas via infected animals or mosquitoes. The consequences of such an introduction will depend on environmental factors, the availability of susceptible ruminants and the capacity of local mosquitoes to transmit the virus. We have previously demonstrated that lambs native to the Netherlands are highly susceptible to RVFV and we here report the vector competence of Culex (Cx.) pipiens, the most abundant and widespread mosquito species in the country. Vector competence was first determined after artificial blood feeding of laboratory-reared mosquitoes using the attenuated Clone 13 strain. Subsequently, experiments with wild-type RVFV and mosquitoes hatched from field-collected eggs were performed. Finally, the transmission of RVFV from viremic lambs to mosquitoes was studied. Artificial feeding experiments using Clone 13 demonstrated that indigenous, laboratory-reared Cx. pipiens mosquitoes are susceptible to RVFV and that the virus can be transmitted via their saliva. Experiments with wild-type RVFV and mosquitoes hatched from field-collected eggs confirmed the vector competence of Cx. pipiens mosquitoes from the Netherlands. To subsequently investigate transmission of the virus under more natural conditions, mosquitoes were allowed to feed on RVFV-infected lambs during the viremic period. We found that RVFV is efficiently transmitted from lambs to mosquitoes, although transmission was restricted to peak viremia. Interestingly, in the mosquito-exposed skin samples, replication of RVFV was detected in previously unrecognized target cells. We here report the vector competence of Cx. pipiens mosquitoes from the Netherlands for RVFV. Both laboratory

Molecular epidemiology of infectious hematopoietic necrosis virus reveals complex virus traffic and evolution within southern Idaho aquaculture

USGS Publications Warehouse

Troyer, R.M.; Kurath, G.

2003-01-01

Infectious hematopoietic necrosis virus (IHNV) is a rhabdovirus which infects salmon and trout and may cause disease with up to 90% mortality. In the Hagerman Valley of Idaho, IHNV is endemic or epidemic among numerous fish farms and resource mitigation hatcheries. A previous study characterizing the genetic diversity among 84 IHNV isolates at 4 virus-endemic rainbow trout farms indicated that multiple lineages of relatively high diversity co-circulated at these facilities (Troyer et al. 2000 J Gen Virol. 81:2823-2832). We tested the hypothesis that high IHNV genetic diversity and co-circulating lineages are present in aquaculture facilities throughout this region. In this study, 73 virus isolates from 14 rainbow trout farms and 3 state hatcheries in the Hagerman Valley, isolated between 1978 and 1999, were genetically characterized by sequence analysis of a 303 nucleotide region of the glycoprotein gene. Phylogenetic and epidemiological analyses showed that multiple IHNV lineages co-circulate in a complex pattern throughout private trout farms and state hatcheries in the valley. IHNV maintained within the valley appears to have evolved significantly over the 22 yr study period.

Generation and characterization of a recombinant Rift Valley fever virus expressing a V5 epitope-tagged RNA-dependent RNA polymerase.

PubMed

Brennan, Benjamin; Li, Ping; Elliott, Richard M

2011-12-01

The viral RNA-dependent RNA polymerase (RdRp; L protein) of Rift Valley fever virus (RVFV; family Bunyaviridae) is a 238 kDa protein that is crucial for the life cycle of the virus, as it catalyses both transcription of viral mRNAs and replication of the tripartite genome. Despite its importance, little is known about the intracellular distribution of the polymerase or its other roles during infection, primarily because of lack of specific antibodies that recognize L protein. To begin to address these questions we investigated whether the RVFV (MP12 strain) polymerase could tolerate insertion of the V5 epitope, as has been previously demonstrated for the Bunyamwera virus L protein. Insertion of the 14 aa epitope into the polymerase sequence at aa 1852 resulted in a polymerase that retained functionality in a minigenome assay, and we were able to rescue recombinant viruses that expressed the modified L protein by reverse genetics. The L protein could be detected in infected cells by Western blotting with anti-V5 antibodies. Examination of recombinant virus-infected cells by immunofluorescence revealed a punctate perinuclear or cytoplasmic distribution of the polymerase that co-localized with the nucleocapsid protein. The generation of RVFV expressing a tagged RdRp will allow detailed examination of the role of the viral polymerase in the virus life cycle.

A network-based meta-population approach to model Rift Valley fever epidemics

USDA-ARS?s Scientific Manuscript database

Rift Valley fever virus (RVFV) has been expanding its geographical distribution with important implications for both human and animal health. The emergence of Rift Valley fever (RVF) in the Middle East, and its continuing presence in many areas of Africa, has negatively impacted both medical and vet...

A 3-year serological and virological cattle follow-up in Madagascar highlands suggests a non-classical transmission route of Rift Valley fever virus.

PubMed

Nicolas, Gaëlle; Durand, Benoit; Rakotoarimanana, Tafika Tojofaniry; Lacote, Sandra; Chevalier, Véronique; Marianneau, Philippe

2014-02-01

Rift Valley fever virus (RVFV) is a mosquito-borne infection of livestock and human which causes a potentially severe disease. In 2008-2009, a RVF outbreak occurred in a temperate and mountainous area located on the highlands of Madagascar. A three-year cattle follow-up (2009-2011) was conducted in a pilot area of this highland. A seroprevalence rate of 28% was estimated in 2009 and a seroconversion rate of 7% in 2009-2010. A third cross-sectional survey showed a seroconversion rate of 14% in 2010-2011. In 2011 the longitudinal study suggested a RVFV circulation during the year. In this area where vectors density is low and cattle exchanges are linked to the virus local spread, we raise hypotheses that may explain the local persistence of the virus.

Rift Valley fever virus infections in Egyptian cattle and their prevention.

PubMed

Mroz, C; Gwida, M; El-Ashker, M; Ziegler, U; Homeier-Bachmann, T; Eiden, M; Groschup, M H

2017-12-01

Rift Valley fever virus (RVFV) causes consistently severe outbreaks with high public health impacts and economic losses in livestock in many African countries and has also been introduced to Saudi Arabia and Yemen. Egypt with its four large outbreaks in the last 40 years represents the northernmost endemic area of RVFV. The purpose of this study was to provide an insight into the current anti-RVFV antibody status in immunized as well as non-immunized dairy cattle from the Nile Delta of Egypt. During 2013-2015, a total of 4,167 dairy cattle from four governorates including Dakahlia, Damietta, Gharbia and Port Said were investigated. All cattle were born after 2007 and therewith after the last reported Egyptian RVFV outbreak in 2003. The samples derived from vaccinated animals from 26 different dairy farms as well as non-immunized cattle from 27 different smallholding flocks. All samples were examined following a three-part analysis including a commercially available competition ELISA, an in-house immunofluorescence assay and a virus neutralization test. Additionally, a subset of samples was analysed for acute infections using IgM ELISA and real-time reverse transcriptase PCR. The results indicated that the RVFV is still circulating in Egypt as about 10% of the non-immunized animals exhibited RVFV-specific antibodies. Surprisingly, the antibody prevalence in immunized animals was not significantly higher than that in non-vaccinated animals which points out the need for further evaluation of the vaccination programme. Due to the substantial role of livestock in the amplification and transmission of RVFV, further recurrent monitoring of the antibody prevalence in susceptible species is highly warranted. © 2017 Blackwell Verlag GmbH.

High content image-based screening of a protease inhibitor library reveals compounds broadly active against Rift Valley fever virus and other highly pathogenic RNA viruses.

PubMed

Mudhasani, Rajini; Kota, Krishna P; Retterer, Cary; Tran, Julie P; Whitehouse, Chris A; Bavari, Sina

2014-08-01

High content image-based screening was developed as an approach to test a protease inhibitor small molecule library for antiviral activity against Rift Valley fever virus (RVFV) and to determine their mechanism of action. RVFV is the causative agent of severe disease of humans and animals throughout Africa and the Arabian Peninsula. Of the 849 compounds screened, 34 compounds exhibited ≥ 50% inhibition against RVFV. All of the hit compounds could be classified into 4 distinct groups based on their unique chemical backbone. Some of the compounds also showed broad antiviral activity against several highly pathogenic RNA viruses including Ebola, Marburg, Venezuela equine encephalitis, and Lassa viruses. Four hit compounds (C795-0925, D011-2120, F694-1532 and G202-0362), which were most active against RVFV and showed broad-spectrum antiviral activity, were selected for further evaluation for their cytotoxicity, dose response profile, and mode of action using classical virological methods and high-content imaging analysis. Time-of-addition assays in RVFV infections suggested that D011-2120 and G202-0362 targeted virus egress, while C795-0925 and F694-1532 inhibited virus replication. We showed that D011-2120 exhibited its antiviral effects by blocking microtubule polymerization, thereby disrupting the Golgi complex and inhibiting viral trafficking to the plasma membrane during virus egress. While G202-0362 also affected virus egress, it appears to do so by a different mechanism, namely by blocking virus budding from the trans Golgi. F694-1532 inhibited viral replication, but also appeared to inhibit overall cellular gene expression. However, G202-0362 and C795-0925 did not alter any of the morphological features that we examined and thus may prove to be good candidates for antiviral drug development. Overall this work demonstrates that high-content image analysis can be used to screen chemical libraries for new antivirals and to determine their mechanism of action and

High Content Image-Based Screening of a Protease Inhibitor Library Reveals Compounds Broadly Active against Rift Valley Fever Virus and Other Highly Pathogenic RNA Viruses

PubMed Central

Mudhasani, Rajini; Kota, Krishna P.; Retterer, Cary; Tran, Julie P.; Whitehouse, Chris A.; Bavari, Sina

2014-01-01

High content image-based screening was developed as an approach to test a protease inhibitor small molecule library for antiviral activity against Rift Valley fever virus (RVFV) and to determine their mechanism of action. RVFV is the causative agent of severe disease of humans and animals throughout Africa and the Arabian Peninsula. Of the 849 compounds screened, 34 compounds exhibited ≥50% inhibition against RVFV. All of the hit compounds could be classified into 4 distinct groups based on their unique chemical backbone. Some of the compounds also showed broad antiviral activity against several highly pathogenic RNA viruses including Ebola, Marburg, Venezuela equine encephalitis, and Lassa viruses. Four hit compounds (C795-0925, D011-2120, F694-1532 and G202-0362), which were most active against RVFV and showed broad-spectrum antiviral activity, were selected for further evaluation for their cytotoxicity, dose response profile, and mode of action using classical virological methods and high-content imaging analysis. Time-of-addition assays in RVFV infections suggested that D011-2120 and G202-0362 targeted virus egress, while C795-0925 and F694-1532 inhibited virus replication. We showed that D011-2120 exhibited its antiviral effects by blocking microtubule polymerization, thereby disrupting the Golgi complex and inhibiting viral trafficking to the plasma membrane during virus egress. While G202-0362 also affected virus egress, it appears to do so by a different mechanism, namely by blocking virus budding from the trans Golgi. F694-1532 inhibited viral replication, but also appeared to inhibit overall cellular gene expression. However, G202-0362 and C795-0925 did not alter any of the morphological features that we examined and thus may prove to be good candidates for antiviral drug development. Overall this work demonstrates that high-content image analysis can be used to screen chemical libraries for new antivirals and to determine their mechanism of action and

An epidemic of Rift Valley fever in Egypt

PubMed Central

Imam, Imam Z. E.; Karamany, R. El; Darwish, Medhat A.

1979-01-01

During the epidemic of Rift Valley fever (RVF) that occurred in Egypt and other areas of North Africa in 1977, the virus was isolated from various species of domestic animal and rats (Rattus rattus frugivorus) as well as man. The highest number of RVF virus isolates were obtained from sheep; only one isolate was recovered from each of the other species tested, viz. cow, camel, goat, horse, and rat. RVF virus was reisolated from both camel and horse sera, apparently for the first time. PMID:314355

Rift Valley Fever: Recent Insights into Pathogenesis and Prevention▿

PubMed Central

Boshra, Hani; Lorenzo, Gema; Busquets, Núria; Brun, Alejandro

2011-01-01

Rift Valley fever virus (RVFV) is a zoonotic pathogen that primarily affects ruminants but can also be lethal in humans. A negative-stranded RNA virus of the family Bunyaviridae, this pathogen is transmitted mainly via mosquito vectors. RVFV has shown the ability to inflict significant damage to livestock and is also a threat to public health. While outbreaks have traditionally occurred in sub-Saharan Africa, recent outbreaks in the Middle East have raised awareness of the potential of this virus to spread to Europe, Asia, and the Americas. Although the virus was initially characterized almost 80 years ago, the only vaccine approved for widespread veterinary use is an attenuated strain that has been associated with significant pathogenic side effects. However, increased understanding of the molecular biology of the virus over the last few years has led to recent advances in vaccine design and has enabled the development of more-potent prophylactic measures to combat infection. In this review, we discuss several aspects of RVFV, with particular emphasis on the molecular components of the virus and their respective roles in pathogenesis and an overview of current vaccine candidates. Progress in understanding the epidemiology of Rift Valley fever has also enabled prediction of potential outbreaks well in advance, thus providing another tool to combat the physical and economic impact of this disease. PMID:21450816

Nonspreading Rift Valley Fever Virus Infection of Human Dendritic Cells Results in Downregulation of CD83 and Full Maturation of Bystander Cells.

PubMed

Oreshkova, Nadia; Wichgers Schreur, Paul J; Spel, Lotte; Vloet, Rianka P M; Moormann, Rob J M; Boes, Marianne; Kortekaas, Jeroen

2015-01-01

Vaccines based on nonspreading Rift Valley fever virus (NSR) induce strong humoral and robust cellular immune responses with pronounced Th1 polarisation. The present work was aimed to gain insight into the molecular basis of NSR-mediated immunity. Recent studies have demonstrated that wild-type Rift Valley fever virus efficiently targets and replicates in dendritic cells (DCs). We found that NSR infection of cultured human DCs results in maturation of DCs, characterized by surface upregulation of CD40, CD80, CD86, MHC-I and MHC-II and secretion of the proinflammatory cytokines IFN-β, IL-6 and TNF. Interestingly, expression of the most prominent marker of DC maturation, CD83, was consistently downregulated at 24 hours post infection. Remarkably, NSR infection also completely abrogated CD83 upregulation by LPS. Downregulation of CD83 was not associated with reduced mRNA levels or impaired CD83 mRNA transport from the nucleus and could not be prevented by inhibition of the proteasome or endocytic degradation pathways, suggesting that suppression occurs at the translational level. In contrast to infected cells, bystander DCs displayed full maturation as evidenced by upregulation of CD83. Our results indicate that bystander DCs play an important role in NSR-mediated immunity.

NSs protein of rift valley fever virus induces the specific degradation of the double-stranded RNA-dependent protein kinase.

PubMed

Habjan, Matthias; Pichlmair, Andreas; Elliott, Richard M; Overby, Anna K; Glatter, Timo; Gstaiger, Matthias; Superti-Furga, Giulio; Unger, Hermann; Weber, Friedemann

2009-05-01

Rift Valley fever virus (RVFV) continues to cause large outbreaks of acute febrile and often fatal illness among humans and domesticated animals in Africa, Saudi Arabia, and Yemen. The high pathogenicity of this bunyavirus is mainly due to the viral protein NSs, which was shown to prevent transcriptional induction of the antivirally active type I interferons (alpha/beta interferon [IFN-alpha/beta]). Viruses lacking the NSs gene induce synthesis of IFNs and are therefore attenuated, whereas the noninducing wild-type RVFV strains can only be inhibited by pretreatment with IFN. We demonstrate here in vitro and in vivo that a substantial part of the antiviral activity of IFN against RVFV is due to a double-stranded RNA-dependent protein kinase (PKR). PKR-mediated virus inhibition, however, was much more pronounced for the strain Clone 13 with NSs deleted than for the NSs-expressing strain ZH548. In vivo, Clone 13 was nonpathogenic for wild-type (wt) mice but could regain pathogenicity if mice lacked the PKR gene. ZH548, in contrast, killed both wt and PKR knockout mice indiscriminately. ZH548 was largely resistant to the antiviral properties of PKR because RVFV NSs triggered the specific degradation of PKR via the proteasome. The NSs proteins of the related but less virulent sandfly fever Sicilian virus and La Crosse virus, in contrast, had no such anti-PKR activity despite being efficient suppressors of IFN induction. Our data suggest that RVFV NSs has gained an additional anti-IFN function that may explain the extraordinary pathogenicity of this virus.

Rift Valley Fever Virus Lacking the NSs and NSm Genes Is Highly Attenuated, Confers Protective Immunity from Virulent Virus Challenge, and Allows for Differential Identification of Infected and Vaccinated Animals▿

PubMed Central

Bird, Brian H.; Albariño, César G.; Hartman, Amy L.; Erickson, Bobbie Rae; Ksiazek, Thomas G.; Nichol, Stuart T.

2008-01-01

Rift Valley fever (RVF) virus is a mosquito-borne human and veterinary pathogen associated with large outbreaks of severe disease throughout Africa and more recently the Arabian peninsula. Infection of livestock can result in sweeping “abortion storms” and high mortality among young animals. Human infection results in self-limiting febrile disease that in ∼1 to 2% of patients progresses to more serious complications including hepatitis, encephalitis, and retinitis or a hemorrhagic syndrome with high fatality. The virus S segment-encoded NSs and the M segment-encoded NSm proteins are important virulence factors. The development of safe, effective vaccines and tools to screen and evaluate antiviral compounds is critical for future control strategies. Here, we report the successful reverse genetics generation of multiple recombinant enhanced green fluorescent protein-tagged RVF viruses containing either the full-length, complete virus genome or precise deletions of the NSs gene alone or the NSs/NSm genes in combination, thus creating attenuating deletions on multiple virus genome segments. These viruses were highly attenuated, with no detectable viremia or clinical illness observed with high challenge dosages (1.0 × 104 PFU) in the rat lethal disease model. A single-dose immunization regimen induced robust anti-RVF virus immunoglobulin G antibodies (titer, ∼1:6,400) by day 26 postvaccination. All vaccinated animals that were subsequently challenged with a high dose of virulent RVF virus survived infection and could be serologically differentiated from naïve, experimentally infected animals by the lack of NSs antibodies. These rationally designed marker RVF vaccine viruses will be useful tools for in vitro screening of therapeutic compounds and will provide a basis for further development of RVF virus marker vaccines for use in endemic regions or following the natural or intentional introduction of the virus into previously unaffected areas. PMID:18199647

Incorporation of antigens from whole cell lysates and purified virions from MP12 into fluorescence microsphere immunoassays for the detection of antibodies against Rift Valley fever virus

USDA-ARS?s Scientific Manuscript database

Background: The purpose of this study was the development of multiplex fluorescence microsphere immunoassay (FMIA) for the detection of Rift Valley fever virus (RVFV) IgG and IgM antibodies by incorporation of antigens from whole cell lysates and purified virions from MP12. Methods and Findings: Vir...

Rift Valley fever virus infection in golden Syrian hamsters.

PubMed

Scharton, Dionna; Van Wettere, Arnaud J; Bailey, Kevin W; Vest, Zachary; Westover, Jonna B; Siddharthan, Venkatraman; Gowen, Brian B

2015-01-01

Rift Valley fever virus (RVFV) is a formidable pathogen that causes severe disease and abortion in a variety of livestock species and a range of disease in humans that includes hemorrhagic fever, fulminant hepatitis, encephalitis and blindness. The natural transmission cycle involves mosquito vectors, but exposure can also occur through contact with infected fluids and tissues. The lack of approved antiviral therapies and vaccines for human use underlies the importance of small animal models for proof-of-concept efficacy studies. Several mouse and rat models of RVFV infection have been well characterized and provide useful systems for the study of certain aspects of pathogenesis, as well as antiviral drug and vaccine development. However, certain host-directed therapeutics may not act on mouse or rat pathways. Here, we describe the natural history of disease in golden Syrian hamsters challenged subcutaneously with the pathogenic ZH501 strain of RVFV. Peracute disease resulted in rapid lethality within 2 to 3 days of RVFV challenge. High titer viremia and substantial viral loads were observed in most tissues examined; however, histopathology and immunostaining for RVFV antigen were largely restricted to the liver. Acute hepatocellular necrosis associated with a strong presence of viral antigen in the hepatocytes indicates that fulminant hepatitis is the likely cause of mortality. Further studies to assess the susceptibility and disease progression following respiratory route exposure are warranted. The use of the hamsters to model RVFV infection is suitable for early stage antiviral drug and vaccine development studies.

Characterizing the effect of Bortezomib on Rift Valley Fever Virus multiplication.

PubMed

Keck, Forrest; Amaya, Moushimi; Kehn-Hall, Kylene; Roberts, Brian; Bailey, Charles; Narayanan, Aarthi

2015-08-01

Rift Valley Fever Virus (RVFV) belongs to the family Bunyaviridae and is a known cause of epizootics and epidemics in Africa and the Middle East. With no FDA approved therapeutics available to treat RVFV infection, understanding the interactions between the virus and the infected host is crucial to developing novel therapeutic strategies. Here, we investigated the requirement of the ubiquitin-proteasome system (UPS) for the establishment of a productive RVFV infection. It was previously shown that the UPS plays a central role in RVFV multiplication involving degradation of PKR and p62 subunit of TFIIH. Using the FDA-approved proteasome inhibitor Bortezomib, we observed robust inhibition of intracellular and extracellular viral loads. Bortezomib treatment did not affect the nuclear/cytoplasmic distribution of the non-structural S-segment protein (NSs); however, the ability of NSs to form nuclear filaments was abolished as a result of Bortezomib treatment. In silico ubiquitination prediction analysis predicted that known NSs interactors (SAP30, YY1, and mSin3A) have multiple putative ubiquitination sites, while NSs itself was not predicted to be ubiquitinated. Immunoprecipitation studies indicated a decrease in interaction between SAP30 - NSs, and mSin3A - NSs in the context of Bortezomib treatment. This decrease in association between SAP30 - NSs also correlated with a decrease in the ubiquitination status of SAP30 with Bortezomib treatment. Bortezomib treatment, however, resulted in increased ubiquitination of mSin3A, suggesting that Bortezomib dynamically affects the ubiquitination status of host proteins that interact with NSs. Finally, we observed that expression of interferon beta (IFN-β) was increased in Bortezomib treated cells which indicated that the cellular antiviral mechanism was revived as a result of treatment and may contribute to control of viral multiplication. Copyright © 2015 Elsevier B.V. All rights reserved.

A glycoprotein subunit vaccine elicits a strong Rift Valley fever virus neutralizing antibody response in sheep.

PubMed

Faburay, Bonto; Lebedev, Maxim; McVey, D Scott; Wilson, William; Morozov, Igor; Young, Alan; Richt, Juergen A

2014-10-01

Rift Valley fever virus (RVFV), a member of the Bunyaviridae family, is a mosquito-borne zoonotic pathogen that causes serious morbidity and mortality in livestock and humans. The recent spread of the virus beyond its traditional endemic boundaries in Africa to the Arabian Peninsula coupled with the presence of susceptible vectors in nonendemic countries has created increased interest in RVF vaccines. Subunit vaccines composed of specific virus proteins expressed in eukaryotic or prokaryotic expression systems are shown to elicit neutralizing antibodies in susceptible hosts. RVFV structural proteins, amino-terminus glycoprotein (Gn), and carboxyl-terminus glycoprotein (Gc), were expressed using a recombinant baculovirus expression system. The recombinant proteins were reconstituted as a GnGc subunit vaccine formulation and evaluated for immunogenicity in a target species, sheep. Six sheep were each immunized with a primary dose of 50 μg of each vaccine immunogen with the adjuvant montanide ISA25; at day 21, postvaccination, each animal received a second dose of the same vaccine. The vaccine induced a strong antibody response in all animals as determined by indirect enzyme-linked immunosorbent assay (ELISA). A plaque reduction neutralization test (PRNT80) showed the primary dose of the vaccine was sufficient to elicit potentially protective virus neutralizing antibody titers ranging from 40 to 160, and the second vaccine dose boosted the titer to more than 1280. Furthermore, all animals tested positive for neutralizing antibodies at day 328 postvaccination. ELISA analysis using the recombinant nucleocapsid protein as a negative marker antigen indicated that the vaccine candidate is DIVA (differentiating infected from vaccinated animals) compatible and represents a promising vaccine platform for RVFV infection in susceptible species.

A Glycoprotein Subunit Vaccine Elicits a Strong Rift Valley Fever Virus Neutralizing Antibody Response in Sheep

PubMed Central

Lebedev, Maxim; McVey, D. Scott; Wilson, William; Morozov, Igor; Young, Alan

2014-01-01

Abstract Rift Valley fever virus (RVFV), a member of the Bunyaviridae family, is a mosquito-borne zoonotic pathogen that causes serious morbidity and mortality in livestock and humans. The recent spread of the virus beyond its traditional endemic boundaries in Africa to the Arabian Peninsula coupled with the presence of susceptible vectors in nonendemic countries has created increased interest in RVF vaccines. Subunit vaccines composed of specific virus proteins expressed in eukaryotic or prokaryotic expression systems are shown to elicit neutralizing antibodies in susceptible hosts. RVFV structural proteins, amino-terminus glycoprotein (Gn), and carboxyl-terminus glycoprotein (Gc), were expressed using a recombinant baculovirus expression system. The recombinant proteins were reconstituted as a GnGc subunit vaccine formulation and evaluated for immunogenicity in a target species, sheep. Six sheep were each immunized with a primary dose of 50 μg of each vaccine immunogen with the adjuvant montanide ISA25; at day 21, postvaccination, each animal received a second dose of the same vaccine. The vaccine induced a strong antibody response in all animals as determined by indirect enzyme-linked immunosorbent assay (ELISA). A plaque reduction neutralization test (PRNT80) showed the primary dose of the vaccine was sufficient to elicit potentially protective virus neutralizing antibody titers ranging from 40 to 160, and the second vaccine dose boosted the titer to more than 1280. Furthermore, all animals tested positive for neutralizing antibodies at day 328 postvaccination. ELISA analysis using the recombinant nucleocapsid protein as a negative marker antigen indicated that the vaccine candidate is DIVA (differentiating infected from vaccinated animals) compatible and represents a promising vaccine platform for RVFV infection in susceptible species. PMID:25325319

Rift valley fever virus nonstructural protein NSs promotes viral RNA replication and transcription in a minigenome system.

PubMed

Ikegami, Tetsuro; Peters, C J; Makino, Shinji

2005-05-01

Rift Valley fever virus (RVFV), which belongs to the genus Phlebovirus, family Bunyaviridae, has a tripartite negative-strand genome (S, M, and L segments) and is an important mosquito-borne pathogen for domestic animals and humans. We established an RVFV T7 RNA polymerase-driven minigenome system in which T7 RNA polymerase from an expression plasmid drove expression of RNA transcripts for viral proteins and minigenome RNA transcripts carrying a reporter gene between both termini of the M RNA segment in 293T cells. Like other viruses of the Bunyaviridae family, replication and transcription of the RVFV minigenome required expression of viral N and L proteins. Unexpectedly, the coexpression of an RVFV nonstructural protein, NSs, with N and L proteins resulted in a significant enhancement of minigenome RNA replication. Coexpression of NSs protein with N and L proteins also enhanced minigenome mRNA transcription in the cells expressing viral-sense minigenome RNA transcripts. NSs protein expression increased the RNA replication of minigenomes that originated from S and L RNA segments. Enhancement of minigenome RNA synthesis by NSs protein occurred in cells lacking alpha/beta interferon (IFN-alpha/beta) genes, indicating that the effect of NSs protein on minigenome RNA replication was unrelated to a putative NSs protein-induced inhibition of IFN-alpha/beta production. Our finding that RVFV NSs protein augmented minigenome RNA synthesis was in sharp contrast to reports that Bunyamwera virus (genus Bunyavirus) NSs protein inhibits viral minigenome RNA synthesis, suggesting that RVFV NSs protein and Bunyamwera virus NSs protein have distinctly different biological roles in viral RNA synthesis.

Rift Valley fever MP-12 vaccine Phase 2 clinical trial: Safety, immunogenicity, and genetic characterization of virus isolates.

PubMed

Pittman, Phillip R; Norris, Sarah L; Brown, Elizabeth S; Ranadive, Manmohan V; Schibly, Barbara A; Bettinger, George E; Lokugamage, Nandadeva; Korman, Lawrence; Morrill, John C; Peters, Clarence J

2016-01-20

An outbreak or deliberate release of Rift Valley fever (RVF) virus could have serious public health and socioeconomic consequences. A safe RVF vaccine capable of eliciting long-lasting immunity after a single injection is urgently needed. The live attenuated RVF MP-12 vaccine candidate has shown promise in Phase 1 clinical trials; no evidence of reversion to virulence has been identified in numerous animal studies. The objective of this Phase 2 clinical trial was to (a) further examine the safety and immunogenicity of RVF MP-12 in RVF virus-naïve humans and (b) characterize isolates of RVF MP-12 virus recovered from the blood of vaccinated subjects to evaluate the genetic stability of MP-12 attenuation. We found that RVF MP-12 was well tolerated, causing mostly mild reactions that resolved without sequelae. Of 19 subjects, 18 (95%) and 19 (100%) achieved, respectively, 80% and 50% plaque reduction neutralization titers (PRNT80 and PRNT50)≥1:20 by postvaccination day 28. All 18 PRNT80 responders maintained PRNT80 and PRNT50≥1:40 until at least postvaccination month 12. Viremia was undetectable in the plasma of any subject by direct plaque assay techniques. However, 5 of 19 vaccinees were positive for MP-12 isolates in plasma by blind passage of plasma on Vero cells. Vaccine virus was also recovered from buffy coat material from one of those vaccinees and from one additional vaccinee. Through RNA sequencing of MP-12 isolates, we found no reversions of amino acids to those of the parent virulent virus (strain ZH548). Five years after a single dose of RVF MP-12 vaccine, 8 of 9 vaccinees (89%) maintained a PRNT80≥1:20. These findings support the continued development of RVF MP-12 as a countermeasure against RVF virus in humans. Published by Elsevier Ltd.

Rift Valley fever outbreak, Mauritania, 1998: seroepidemiologic, virologic, entomologic, and zoologic investigations.

PubMed

Nabeth, P; Kane, Y; Abdalahi, M O; Diallo, M; Ndiaye, K; Ba, K; Schneegans, F; Sall, A A; Mathiot, C

2001-01-01

A Rift Valley fever outbreak occurred in Mauritania in 1998. Seroepidemiologic and virologic investigation showed active circulation of the Rift Valley fever virus, with 13 strains isolated, and 16% (range 1.5%-38%) immunoglobulin (Ig) M-positivity in sera from 90 humans and 343 animals (sheep, goats, camels, cattle, and donkeys). One human case was fatal.

Development and characterization of a Rift Valley fever virus cell-cell fusion assay using alphavirus replicon vectors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Filone, Claire Marie; Heise, Mark; Doms, Robert W.

2006-12-20

Rift Valley fever virus (RVFV), a member of the Phlebovirus genus in the Bunyaviridae family, is transmitted by mosquitoes and infects both humans and domestic animals, particularly cattle and sheep. Since primary RVFV strains must be handled in BSL-3+ or BSL-4 facilities, a RVFV cell-cell fusion assay will facilitate the investigation of RVFV glycoprotein function under BSL-2 conditions. As for other members of the Bunyaviridae family, RVFV glycoproteins are targeted to the Golgi, where the virus buds, and are not efficiently delivered to the cell surface. However, overexpression of RVFV glycoproteins using an alphavirus replicon vector resulted in the expressionmore » of the glycoproteins on the surface of multiple cell types. Brief treatment of RVFV glycoprotein expressing cells with mildly acidic media (pH 6.2 and below) resulted in rapid and efficient syncytia formation, which we quantified by {beta}-galactosidase {alpha}-complementation. Fusion was observed with several cell types, suggesting that the receptor(s) for RVFV is widely expressed or that this acid-dependent virus does not require a specific receptor to mediate cell-cell fusion. Fusion occurred over a broad temperature range, as expected for a virus with both mosquito and mammalian hosts. In contrast to cell fusion mediated by the VSV-G glycoprotein, RVFV glycoprotein-dependent cell fusion could be prevented by treating target cells with trypsin, indicating that one or more proteins (or protein-associated carbohydrate) on the host cell surface are needed to support membrane fusion. The cell-cell fusion assay reported here will make it possible to study the membrane fusion activity of RVFV glycoproteins in a high-throughput format and to screen small molecule inhibitors for the ability to block virus-specific membrane fusion.« less

Rescue of infectious rift valley fever virus entirely from cDNA, analysis of virus lacking the NSs gene, and expression of a foreign gene.

PubMed

Ikegami, Tetsuro; Won, Sungyong; Peters, C J; Makino, Shinji

2006-03-01

Rift Valley fever virus (RVFV) (genus Phlebovirus, family Bunyaviridae) has a tripartite negative-strand genome, causes a mosquito-borne disease that is endemic in sub-Saharan African countries and that also causes large epidemics among humans and livestock. Furthermore, it is a bioterrorist threat and poses a risk for introduction to other areas. In spite of its danger, neither veterinary nor human vaccines are available. We established a T7 RNA polymerase-driven reverse genetics system to rescue infectious clones of RVFV MP-12 strain entirely from cDNA, the first for any phlebovirus. Expression of viral structural proteins from the protein expression plasmids was not required for virus rescue, whereas NSs protein expression abolished virus rescue. Mutants of MP-12 partially or completely lacking the NSs open reading frame were viable. These NSs deletion mutants replicated efficiently in Vero and 293 cells, but not in MRC-5 cells. In the latter cell line, accumulation of beta interferon mRNA occurred after infection by these NSs deletion mutants, but not after infection by MP-12. The NSs deletion mutants formed larger plaques than MP-12 did in Vero E6 cells and failed to shut off host protein synthesis in Vero cells. An MP-12 mutant carrying a luciferase gene in place of the NSs gene replicated as efficiently as MP-12 did, produced enzymatically active luciferase during replication, and stably retained the luciferase gene after 10 virus passages, representing the first demonstration of foreign gene expression in any bunyavirus. This reverse genetics system can be used to study the molecular virology of RVFV, assess current vaccine candidates, produce new vaccines, and incorporate marker genes into animal vaccines.

Favipiravir (T-705) protects against peracute Rift Valley fever virus infection and reduces delayed-onset neurologic disease observed with ribavirin treatment.

PubMed

Scharton, Dionna; Bailey, Kevin W; Vest, Zachary; Westover, Jonna B; Kumaki, Yohichi; Van Wettere, Arnaud; Furuta, Yousuke; Gowen, Brian B

2014-04-01

Rift Valley fever is a zoonotic, arthropod-borne disease that affects livestock and humans. The etiologic agent, Rift Valley fever virus (RVFV; Bunyaviridae, Phlebovirus) is primarily transmitted through mosquito bites, but can also be transmitted by exposure to infectious aerosols. There are presently no licensed vaccines or therapeutics to prevent or treat severe RVFV infection in humans. We have previously reported on the activity of favipiravir (T-705) against the MP-12 vaccine strain of RVFV and other bunyaviruses in cell culture. In addition, efficacy has also been documented in mouse and hamster models of infection with the related Punta Toro virus. Here, hamsters challenged with the highly pathogenic ZH501 strain of RVFV were used to evaluate the activity of favipiravir against lethal infection. Subcutaneous RVFV challenge resulted in substantial serum and tissue viral loads and caused severe disease and mortality within 2-3 days of infection. Oral favipiravir (200 mg/kg/day) prevented mortality in 60% or greater of hamsters challenged with RVFV when administered within 1 or 6h post-exposure and reduced RVFV titers in serum and tissues relative to the time of treatment initiation. In contrast, although ribavirin (75 mg/kg/day) was effective at protecting animals from the peracute RVFV disease, most ultimately succumbed from a delayed-onset neurologic disease associated with high RVFV burden observed in the brain in moribund animals. When combined, T-705 and ribavirin treatment started 24 h post-infection significantly improved survival outcome and reduced serum and tissue virus titers compared to monotherapy. Our findings demonstrate significant post-RVFV exposure efficacy with favipiravir against both peracute disease and delayed-onset neuroinvasion, and suggest added benefit when combined with ribavirin. Copyright © 2014 Elsevier B.V. All rights reserved.

Novel approaches to develop Rift Valley fever vaccines

PubMed Central

Indran, Sabarish V.; Ikegami, Tetsuro

2012-01-01

Rift Valley fever (RVF) is endemic to sub-Saharan Africa, and has spread into Madagascar, Egypt, Saudi Arabia, and Yemen. Rift Valley fever virus (RVFV) of the family Bunyaviridae, genus Phlebovirus causes hemorrhagic fever, neurological disorders or blindness in humans, and high rate abortion and fetal malformation in ruminants. RVFV is classified as a Category A Priority pathogen and overlap select agent by CDC/USDA due to its potential impact on public health and agriculture. There is a gap in the safety and immunogenicity in traditional RVF vaccines; the formalin-inactivated RVFV vaccine TSI-GSD-200 requires three doses for protection, and the live-attenuated Smithburn vaccine has a risk to cause abortion and fetal malformation in pregnant ruminants. In this review, problems of traditional vaccines and the safety and efficacy of recently reported novel RVF candidate vaccines including subunit vaccines, virus vector, and replicons are discussed. PMID:23112960

Novel approaches to develop Rift Valley fever vaccines.

PubMed

Indran, Sabarish V; Ikegami, Tetsuro

2012-01-01

Rift Valley fever (RVF) is endemic to sub-Saharan Africa, and has spread into Madagascar, Egypt, Saudi Arabia, and Yemen. Rift Valley fever virus (RVFV) of the family Bunyaviridae, genus Phlebovirus causes hemorrhagic fever, neurological disorders or blindness in humans, and high rate abortion and fetal malformation in ruminants. RVFV is classified as a Category A Priority pathogen and overlap select agent by CDC/USDA due to its potential impact on public health and agriculture. There is a gap in the safety and immunogenicity in traditional RVF vaccines; the formalin-inactivated RVFV vaccine TSI-GSD-200 requires three doses for protection, and the live-attenuated Smithburn vaccine has a risk to cause abortion and fetal malformation in pregnant ruminants. In this review, problems of traditional vaccines and the safety and efficacy of recently reported novel RVF candidate vaccines including subunit vaccines, virus vector, and replicons are discussed.

MP-12 virus containing the clone 13 deletion in the NSs gene prevents lethal disease when administered after Rift Valley fever virus infection in hamsters.

PubMed

Gowen, Brian B; Westover, Jonna B; Sefing, Eric J; Bailey, Kevin W; Nishiyama, Shoko; Wandersee, Luci; Scharton, Dionna; Jung, Kie-Hoon; Ikegami, Tetsuro

2015-01-01

Rift Valley fever virus (RVFV; Bunyaviridae, Phlebovirus) causes a range of illnesses that include retinitis, fulminant hepatitis, neurologic disease, and hemorrhagic fever. In hospitalized individuals, case fatality rates can be as high as 10-20%. There are no vaccines or antivirals approved for human use to prevent or treat severe RVFV infections. We previously tested the efficacy of the MP-12 vaccine strain and related variants with NSs truncations as a post-exposure prophylaxis in mice infected with wild-type pathogenic RVFV strain ZH501. Post-exposure efficacy of the rMP12-C13type, a recombinant MP-12 vaccine virus which encodes an in-frame truncation removing 69% of the NSs protein, resulted in 30% survival when administering the virus within 30 min of subcutaneous ZH501 challenge in mice, while the parental MP-12 virus conferred no protection by post-exposure vaccination. Here, we demonstrate uniform protection of hamsters by post-exposure vaccination with rMP12-C13type administered 6 h post-ZH501 infection while no efficacy was observed with the parental MP-12 virus. Notably, both the MP-12 and rMP12-C13type viruses were highly effective (100% protection) when administered 21 days prior to challenge. In a subsequent study delaying vaccination until 8, 12, and 24 h post-RVFV exposure, we observed 80, 70, and 30% survival, respectively. Our findings indicate that the rapid protective innate immune response elicited by rMP12-C13type may be due to the truncated NSs protein, suggesting that the resulting functional inactivation of NSs plays an important role in the observed post-exposure efficacy. Taken together, the data demonstrate that post-exposure vaccination with rMP12-C13type is effective in limiting ZH501 replication and associated disease in standard pre-exposure vaccination and post-challenge treatment models of RVFV infection, and suggest an extended post-exposure prophylaxis window beyond that initially observed in mice.

An equine herpesvirus type 1 (EHV-1) vector expressing Rift Valley fever virus (RVFV) Gn and Gc induces neutralizing antibodies in sheep.

PubMed

Said, Abdelrahman; Elmanzalawy, Mona; Ma, Guanggang; Damiani, Armando Mario; Osterrieder, Nikolaus

2017-08-14

Rift Valley fever virus (RVFV) is an arthropod-borne bunyavirus that can cause serious and fatal disease in humans and animals. RVFV is a negative-sense RNA virus of the Phlebovirus genus in the Bunyaviridae family. The main envelope RVFV glycoproteins, Gn and Gc, are encoded on the M segment of RVFV and known inducers of protective immunity. In an attempt to develop a safe and efficacious RVF vaccine, we constructed and tested a vectored equine herpesvirus type 1 (EHV-1) vaccine that expresses RVFV Gn and Gc. The Gn and Gc genes were custom-synthesized after codon optimization and inserted into EHV-1 strain RacH genome. The rH_Gn-Gc recombinant virus grew in cultured cells with kinetics that were comparable to those of the parental virus and stably expressed Gn and Gc. Upon immunization of sheep, the natural host, neutralizing antibodies against RVFV were elicited by rH_Gn-Gc and protective titers reached to 1:320 at day 49 post immunization but not by parental EHV-1, indicating that EHV-1 is a promising vector alternative in the development of a safe marker RVFV vaccine.

Reemergence of Rift Valley fever, Mauritania, 2010.

PubMed

Faye, Ousmane; Ba, Hampathé; Ba, Yamar; Freire, Caio C M; Faye, Oumar; Ndiaye, Oumar; Elgady, Isselmou O; Zanotto, Paolo M A; Diallo, Mawlouth; Sall, Amadou A

2014-02-01

A Rift Valley fever (RVF) outbreak in humans and animals occurred in Mauritania in 2010. Thirty cases of RVF in humans and 3 deaths were identified. RVFV isolates were recovered from humans, camels, sheep, goats, and Culex antennatus mosquitoes. Phylogenetic analysis of isolates indicated a virus origin from western Africa.

Rift Valley fever: a mosquito-borne emerging disease

USDA-ARS?s Scientific Manuscript database

Rift Valley fever (RVF) (Bunyaviridae: Phlebovirus) is mosquito-borne zoonotic emerging infectious viral disease caused by RVF virus (RVFV) that presents significant threats to global public health and agriculture in Africa and the Middle East. RVFV is listed as a select agent with significant conce...

Spectrum of Rift Valley Fever Virus Transmission in Kenya: Insights from three Distinct Regions

PubMed Central

Labeaud, A. Desiree; Ochiai, Yoshitsugu; Peters, C.J.; Muchiri, Eric M.; King, Charles H.

2008-01-01

Rift Valley fever virus (RVFV) is an emerging pathogen that maintains high biodefense priority based on its threat to livestock, its ability to cause human hemorrhagic fever, and its potential for aerosol spread. To define the range of human transmission during inter-epidemic and epidemic periods in Kenya, we tested archived sera from defined populations (N = 1,263) for anti-RVFV IgG by ELISA and plaque reduction neutralization testing. RVFV seroprevalence was 10.8% overall and varied significantly by location, sex, and age. In NW Kenya, high seroprevalence among those born before 1980 indicates that an undetected epidemic may have occurred then. Seroconversion documented in highland areas suggests previously unsuspected inter-epidemic transmission. RVFV seroprevalence is strikingly high in certain Kenyan areas, suggesting endemic transmission patterns that may preclude accurate estimation of regional acute outbreak incidence. The extent of both epidemic and inter-epidemic RVFV transmission in Kenya is greater than previously documented. PMID:17488893

Multiplex Detection of IgG and IgM to Rift Valley Fever Virus Nucleoprotein, Nonstructural Proteins, and Glycoprotein in Ovine and Bovine.

PubMed

Hossain, Mohammad M; Wilson, William C; Faburay, Bonto; Richt, Jürgen; McVey, David S; Rowland, Raymond R

2016-08-01

A multiplex fluorescence microsphere immunoassay (FMIA) was used to detect bovine and ovine IgM and IgG antibodies to several Rift Valley fever virus (RVFV) proteins, including the major surface glycoprotein, Gn; the nonstructural proteins, NSs and NSm; and the nucleoprotein, N. Target antigens were assembled into a multiplex and tested in serum samples from infected wild-type RVFV or MP12, a modified live virus vaccine. As expected, the N protein was immunodominant and the best target for early detection of infection. Antibody activity against the other targets was also detected. The experimental results demonstrate the capabilities of FMIA for the detection of antibodies to RVFV structural and nonstructural proteins, which can be applied to future development and validation of diagnostic tests that can be used to differentiate vaccinated from infected animals.

Rift Valley Fever Virus Control: Integration of Virus, Host and Vector Studies

USDA-ARS?s Scientific Manuscript database

Rift Valley fever (RVF) is a disease of animals and humans that occurs in Africa and the Arabian Peninsula. It is caused by a Phlebovirus in the family Bunyaviridae. Mosquito-borne epizootics occur during years of unusually heavy rainfall. Domestic cattle, sheep and goats are highly susceptible to i...

Phosphoproteomic analysis reveals Smad protein family activation following Rift Valley fever virus infection.

PubMed

de la Fuente, Cynthia; Pinkham, Chelsea; Dabbagh, Deemah; Beitzel, Brett; Garrison, Aura; Palacios, Gustavo; Hodge, Kimberley Alex; Petricoin, Emanuel F; Schmaljohn, Connie; Campbell, Catherine E; Narayanan, Aarthi; Kehn-Hall, Kylene

2018-01-01

Rift Valley fever virus (RVFV) infects both ruminants and humans leading to a wide variance of pathologies dependent on host background and age. Utilizing a targeted reverse phase protein array (RPPA) to define changes in signaling cascades after in vitro infection of human cells with virulent and attenuated RVFV strains, we observed high phosphorylation of Smad transcription factors. This evolutionarily conserved family is phosphorylated by and transduces the activation of TGF-β superfamily receptors. Moreover, we observed that phosphorylation of Smad proteins required active RVFV replication and loss of NSs impaired this activation, further corroborating the RPPA results. Gene promoter analysis of transcripts altered after RVFV infection identified 913 genes that contained a Smad-response element. Functional annotation of these potential Smad-regulated genes clustered in axonal guidance, hepatic fibrosis and cell signaling pathways involved in cellular adhesion/migration, calcium influx, and cytoskeletal reorganization. Furthermore, chromatin immunoprecipitation confirmed the presence of a Smad complex on the interleukin 1 receptor type 2 (IL1R2) promoter, which acts as a decoy receptor for IL-1 activation.

Rift valley fever in the US: Commerce networks, climate, and susceptible vector and host populations

USDA-ARS?s Scientific Manuscript database

Rift Valley fever (RVF) is a mosquito-borne hemorrhagic viral disease with substantial negative impacts on public and animal health in its endemic range of sub-Saharan Africa. Rift Valley fever virus (RVFV) could enter the United States and lead to widespread morbidity and mortality in humans, domes...

Serological evidence of rift valley fever virus among acute febrile patients in Southern Mozambique during and after the 2013 heavy rainfall and flooding: implication for the management of febrile illness.

PubMed

Gudo, Eduardo Samo; Pinto, Gabriela; Weyer, Jacqueline; le Roux, Chantel; Mandlaze, Arcildo; José, Américo Feriano; Muianga, Argentina; Paweska, Janusz Tadeusz

2016-06-08

Rift Valley fever virus (RVFV) remains heavily neglected in humans in Mozambique, even though recent outbreaks were reported in neighboring countries in humans and several cases of RVFV in cattle were reported in several districts in Mozambique. We conducted a cross sectional study during and after severe flooding that occurred in 2013 in Mozambique. Paired acute and convalescent serum samples were tested from febrile patients attending a primary health care unit in a suburban area of Maputo city for the presence of IgG and IgM antibodies against Rift Valley fever virus (RVFV) using enzyme-linked immunosorbent assay (ELISA). Seroconversion of IgG anti-RVFV was observed in 5 % (10/200) of convalescent patients and specific IgM anti-RVFV was detected in one acute patient (0.5 %; 1/200). All sera from acute patient tested negative by real time PCR. In conclusion, our results suggest that RVF represent an important but neglected cause of febrile illness following periods of flooding in southern Mozambique.

Mapping the Risk of Rift Valley fever re-emergence in Southern Africa using remote sensing data

USDA-ARS?s Scientific Manuscript database

Rift Valley fever is a viral disease of animals and humans that occurs throughout sub-Saharan Africa, Egypt and the Arabian Peninsula. Outbreaks of the disease are episodic and closely linked to climate variability, especially widespread elevated rainfall that facilitates Rift Valley fever virus tra...

Analysis of surveillance systems in place in European Mediterranean countries for West Nile virus (WNV) and Rift Valley fever (RVF).

PubMed

Cito, F; Narcisi, V; Danzetta, M L; Iannetti, S; Sabatino, D D; Bruno, R; Carvelli, A; Atzeni, M; Sauro, F; Calistri, P

2013-11-01

West Nile virus (WNV) and Rift Valley fever virus (RVFV) represent an important group of viral agents responsible for vector-borne zoonotic diseases constituting an emerging sanitary threat for the Mediterranean Basin and the neighbouring countries. WNV infection is present in several Mediterranean countries, whereas RVF has never been introduced into Europe, but it is considered a major threat for North African countries. Being vector-borne diseases, they cannot be prevented only through an animal trade control policy. Several approaches are used for the surveillance of WNV and RVFV. With the aim of assessing the surveillance systems in place in Mediterranean countries, two disease-specific questionnaires (WNV, RVFV) have been prepared and submitted to Public Health and Veterinary Authorities of six EU countries. This study presents the information gathered through the questionnaires and describes some critical points in the prevention and surveillance of these diseases as emerged by the answers received. © 2013 Blackwell Verlag GmbH.

Rift Valley Fever, Mayotte, 2007–2008

PubMed Central

Giry, Claude; Gabrie, Philippe; Tarantola, Arnaud; Pettinelli, François; Collet, Louis; D’Ortenzio, Eric; Renault, Philippe; Pierre, Vincent

2009-01-01

After the 2006–2007 epidemic wave of Rift Valley fever (RVF) in East Africa and its circulation in the Comoros, laboratory case-finding of RVF was conducted in Mayotte from September 2007 through May 2008. Ten recent human RVF cases were detected, which confirms the indigenous transmission of RFV virus in Mayotte. PMID:19331733

Unexpected Rift Valley Fever Outbreak, Northern Mauritania

PubMed Central

El Mamy, Ahmed B. Ould; Baba, Mohamed Ould; Barry, Yahya; Isselmou, Katia; Dia, Mamadou L.; Hampate, Ba; Diallo, Mamadou Y.; El Kory, Mohamed Ould Brahim; Diop, Mariam; Lo, Modou Moustapha; Thiongane, Yaya; Bengoumi, Mohammed; Puech, Lilian; Plee, Ludovic; Claes, Filip; Doumbia, Baba

2011-01-01

During September–October 2010, an unprecedented outbreak of Rift Valley fever was reported in the northern Sahelian region of Mauritania after exceptionally heavy rainfall. Camels probably played a central role in the local amplification of the virus. We describe the main clinical signs (hemorrhagic fever, icterus, and nervous symptoms) observed during the outbreak. PMID:22000364

A hierarchical network approach for modeling Rift Valley fever epidemics with applications in North America

USDA-ARS?s Scientific Manuscript database

Rift Valley fever (RVF) is a vector-borne zoonotic disease which causes high morbidity and mortality in livestock. In the event Rift Valley fever virus is introduced to the United States or other non-endemic areas, understanding the potential patterns of spread and the areas at risk based on disease...

Pathogenesis of Rift Valley Fever in Rhesus Monkeys: Role of Interferon Response

DTIC Science & Technology

1990-01-01

hemorrhagic fever characterized by epistaxis, petechial to purpuric cutaneous lesions, anorexia, and vomiting prior to death. The 14 remaining monkeys survived...DMI, FILE Copy Arch Virol (1990) 110: 195-212 Amhivesirology ( by Springer-Verlag 1990 00 N Pathogenesis of Rift Valley fever in rhesus monkeys: (NI...inoculated intravenously with Rift Valley fever (RVF) virus presented clinical disease syndromes similar to human cases of RVF. All 17 infected monkeys

Genetic Evidence for an Interferon-Antagonistic Function of Rift Valley Fever Virus Nonstructural Protein NSs

PubMed Central

Bouloy, Michèle; Janzen, Christian; Vialat, Pierre; Khun, Huot; Pavlovic, Jovan; Huerre, Michel; Haller, Otto

2001-01-01

Rift Valley fever virus (RVFV), a phlebovirus of the family Bunyaviridae, is a major public health threat in Egypt and sub-Saharan Africa. The viral and host cellular factors that contribute to RVFV virulence and pathogenicity are still poorly understood. All pathogenic RVFV strains direct the synthesis of a nonstructural phosphoprotein (NSs) that is encoded by the smallest (S) segment of the tripartite genome and has an undefined accessory function. In this report, we show that MP12 and clone 13, two attenuated RVFV strains with mutations in the NSs gene, were highly virulent in IFNAR−/− mice lacking the alpha/beta interferon (IFN-α/β) receptor but remained attenuated in IFN-γ receptor-deficient mice. Both attenuated strains proved to be excellent inducers of early IFN-α/β production. In contrast, the virulent strain ZH548 failed to induce detectable amounts of IFN-α/β and replicated extensively in both IFN-competent and IFN-deficient mice. Clone 13 has a defective NSs gene with a large in-frame deletion. This defect in the NSs gene results in expression of a truncated protein which is rapidly degraded. To investigate whether the presence of the wild-type NSs gene correlated with inhibition of IFN-α/β production, we infected susceptible IFNAR−/− mice with S gene reassortant viruses. When the S segment of ZH548 was replaced by that of clone 13, the resulting reassortants became strong IFN inducers. When the defective S segment of clone 13 was exchanged with the wild-type S segment of ZH548, the reassortant virus lost the capacity to stimulate IFN-α/β production. These results demonstrate that the ability of RVFV to inhibit IFN-α/β production correlates with viral virulence and suggest that the accessory protein NSs is an IFN antagonist. PMID:11152510

Rift Valley Fever Virus Circulating among Ruminants, Mosquitoes and Humans in the Central African Republic.

PubMed

Nakouné, Emmanuel; Kamgang, Basile; Berthet, Nicolas; Manirakiza, Alexandre; Kazanji, Mirdad

2016-10-01

Rift Valley fever virus (RVFV) causes a viral zoonosis, with discontinuous epizootics and sporadic epidemics, essentially in East Africa. Infection with this virus causes severe illness and abortion in sheep, goats, and cattle as well as other domestic animals. Humans can also be exposed through close contact with infectious tissues or by bites from infected mosquitoes, primarily of the Aedes and Culex genuses. Although the cycle of RVFV infection in savannah regions is well documented, its distribution in forest areas in central Africa has been poorly investigated. To evaluate current circulation of RVFV among livestock and humans living in the Central African Republic (CAR), blood samples were collected from sheep, cattle, and goats and from people at risk, such as stock breeders and workers in slaughterhouses and livestock markets. The samples were tested for anti-RVFV immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies. We also sequenced the complete genomes of two local strains, one isolated in 1969 from mosquitoes and one isolated in 1985 from humans living in forested areas. The 1271 animals sampled comprised 727 cattle, 325 sheep, and 219 goats at three sites. The overall seroprevalence of anti-RVFV IgM antibodies was 1.9% and that of IgG antibodies was 8.6%. IgM antibodies were found only during the rainy season, but the frequency of IgG antibodies did not differ significantly by season. No evidence of recent RVFV infection was found in 335 people considered at risk; however, 16.7% had evidence of past infection. Comparison of the nucleotide sequences of the strains isolated in the CAR with those isolated in other African countries showed that they belonged to the East/Central African cluster. This study confirms current circulation of RVFV in CAR. Further studies are needed to determine the potential vectors involved and the virus reservoirs.

Genetic Diversity of Toscana Virus

PubMed Central

Collao, Ximena; Palacios, Gustavo; Sanbonmatsu-Gámez, Sara; Pérez-Ruiz, Mercedes; Negredo, Ana I.; Navarro-Marí, José-María; Grandadam, Marc; Aransay, Ana Maria; Lipkin, W. Ian; Tenorio, Antonio

2009-01-01

Distribution of Toscana virus (TOSV) is evolving with climate change, and pathogenicity may be higher in nonexposed populations outside areas of current prevalence (Mediterranean Basin). To characterize genetic diversity of TOSV, we determined the coding sequences of isolates from Spain and France. TOSV is more diverse than other well-studied phleboviruses (e.g.,Rift Valley fever virus). PMID:19331735

Rift Valley Fever.

PubMed

Hartman, Amy

2017-06-01

Rift Valley fever (RVF) is a severe veterinary disease of livestock that also causes moderate to severe illness in people. The life cycle of RVF is complex and involves mosquitoes, livestock, people, and the environment. RVF virus is transmitted from either mosquitoes or farm animals to humans, but is generally not transmitted from person to person. People can develop different diseases after infection, including febrile illness, ocular disease, hemorrhagic fever, or encephalitis. There is a significant risk for emergence of RVF into new locations, which would affect human health and livestock industries. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of age on the pathogenesis of duck tembusu virus in Cherry Valley ducks

PubMed Central

Li, Ning; Lv, Chuanwei; Yue, Ruichao; Shi, Ying; Wei, Liangmeng; Chai, Tongjie; Liu, Sidang

2015-01-01

The effect of host age on the outcome of duck tembusu virus (DTMUV) infection was studied in ducks. Three groups of Cherry Valley ducks at 1, 3, and 7 weeks of age were intramuscularly infected with DTMUV to systematically observe the clinical symptoms, pathological changes, tissue viral loads, and immune responses. Severe clinical symptoms and neurological dysfunction were observed in 1-week-old ducks as early as 2 days post infection (dpi) and some died at 5–7 dpi. Three weeks-old ducks showed similar but milder symptoms and no deaths. However, 7-weeks-old ducks showed only transient loss of appetite. Gross lesions gradually reduced in severity as ducks matured. One-week-old ducks showed endocardial hemorrhage, splenomegaly, swelling in the lymph follicles of the ileum, liver, and kidney swelling with degeneration, and meningeal hyperemia. Three-weeks-old ducks showed only mild pathological lesions. No visible lesions were observed in 7-weeks-old ducks. However, pathological histology analysis demonstrated all infected ducks displayed viral encephalitis. DTMUV could be detected in the brains of 1-week-old ducks as early as 1 dpi and virus titers of most organs in 1-week-old ducks were significantly higher than that of 3- and 7-weeks-old ducks at 3–5 dpi. The patterns of IFN-γ, IL-2, and serum neutralizing antibodies were similar, and there were significant difference between the youngest ducks and the older ducks at early infection stage (P < 0.05). More important is that although the antibody titers of all infected ducks were similar from 9 to 17 dpi, reduced clearance of virus was observed in the youngest groups comparing with the other two groups, indicating that immune system maturity was more important than the presence of neutralizing antibody. In summary, this study demonstrates that viral pathogenesis is strongest in 1-week-old ducks and the age-related immune response plays an important role in the pathogenesis of DTMUV in ducks. PMID:26106382

Effect of age on the pathogenesis of duck tembusu virus in Cherry Valley ducks.

PubMed

Li, Ning; Lv, Chuanwei; Yue, Ruichao; Shi, Ying; Wei, Liangmeng; Chai, Tongjie; Liu, Sidang

2015-01-01

The effect of host age on the outcome of duck tembusu virus (DTMUV) infection was studied in ducks. Three groups of Cherry Valley ducks at 1, 3, and 7 weeks of age were intramuscularly infected with DTMUV to systematically observe the clinical symptoms, pathological changes, tissue viral loads, and immune responses. Severe clinical symptoms and neurological dysfunction were observed in 1-week-old ducks as early as 2 days post infection (dpi) and some died at 5-7 dpi. Three weeks-old ducks showed similar but milder symptoms and no deaths. However, 7-weeks-old ducks showed only transient loss of appetite. Gross lesions gradually reduced in severity as ducks matured. One-week-old ducks showed endocardial hemorrhage, splenomegaly, swelling in the lymph follicles of the ileum, liver, and kidney swelling with degeneration, and meningeal hyperemia. Three-weeks-old ducks showed only mild pathological lesions. No visible lesions were observed in 7-weeks-old ducks. However, pathological histology analysis demonstrated all infected ducks displayed viral encephalitis. DTMUV could be detected in the brains of 1-week-old ducks as early as 1 dpi and virus titers of most organs in 1-week-old ducks were significantly higher than that of 3- and 7-weeks-old ducks at 3-5 dpi. The patterns of IFN-γ, IL-2, and serum neutralizing antibodies were similar, and there were significant difference between the youngest ducks and the older ducks at early infection stage (P < 0.05). More important is that although the antibody titers of all infected ducks were similar from 9 to 17 dpi, reduced clearance of virus was observed in the youngest groups comparing with the other two groups, indicating that immune system maturity was more important than the presence of neutralizing antibody. In summary, this study demonstrates that viral pathogenesis is strongest in 1-week-old ducks and the age-related immune response plays an important role in the pathogenesis of DTMUV in ducks.

Mechanistic Insight into the Host Transcription Inhibition Function of Rift Valley Fever Virus NSs and Its Importance in Virulence

PubMed Central

Terasaki, Kaori; Ramirez, Sydney I.; Makino, Shinji

2016-01-01

Rift Valley fever virus (RVFV), a member of the genus Phlebovirus within the family Bunyaviridae, causes periodic outbreaks in livestocks and humans in countries of the African continent and Middle East. RVFV NSs protein, a nonstructural protein, is a major virulence factor that exhibits several important biological properties. These include suppression of general transcription, inhibition of IFN-β promoter induction and degradation of double-stranded RNA-dependent protein kinase R. Although each of these biological functions of NSs are considered important for countering the antiviral response in the host, the individual contributions of these functions towards RVFV virulence remains unclear. To examine this, we generated two RVFV MP-12 strain-derived mutant viruses. Each carried mutations in NSs that specifically targeted its general transcription inhibition function without affecting its ability to degrade PKR and inhibit IFN-β promoter induction, through its interaction with Sin3-associated protein 30, a part of the repressor complex at the IFN-β promoter. Using these mutant viruses, we have dissected the transcription inhibition function of NSs and examined its importance in RVFV virulence. Both NSs mutant viruses exhibited a differentially impaired ability to inhibit host transcription when compared with MP-12. It has been reported that NSs suppresses general transcription by interfering with the formation of the transcription factor IIH complex, through the degradation of the p62 subunit and sequestration of the p44 subunit. Our study results lead us to suggest that the ability of NSs to induce p62 degradation is the major contributor to its general transcription inhibition property, whereas its interaction with p44 may not play a significant role in this function. Importantly, RVFV MP-12-NSs mutant viruses with an impaired general transcription inhibition function showed a reduced cytotoxicity in cell culture and attenuated virulence in young mice

Mechanistic Insight into the Host Transcription Inhibition Function of Rift Valley Fever Virus NSs and Its Importance in Virulence.

PubMed

Terasaki, Kaori; Ramirez, Sydney I; Makino, Shinji

2016-10-01

Rift Valley fever virus (RVFV), a member of the genus Phlebovirus within the family Bunyaviridae, causes periodic outbreaks in livestocks and humans in countries of the African continent and Middle East. RVFV NSs protein, a nonstructural protein, is a major virulence factor that exhibits several important biological properties. These include suppression of general transcription, inhibition of IFN-β promoter induction and degradation of double-stranded RNA-dependent protein kinase R. Although each of these biological functions of NSs are considered important for countering the antiviral response in the host, the individual contributions of these functions towards RVFV virulence remains unclear. To examine this, we generated two RVFV MP-12 strain-derived mutant viruses. Each carried mutations in NSs that specifically targeted its general transcription inhibition function without affecting its ability to degrade PKR and inhibit IFN-β promoter induction, through its interaction with Sin3-associated protein 30, a part of the repressor complex at the IFN-β promoter. Using these mutant viruses, we have dissected the transcription inhibition function of NSs and examined its importance in RVFV virulence. Both NSs mutant viruses exhibited a differentially impaired ability to inhibit host transcription when compared with MP-12. It has been reported that NSs suppresses general transcription by interfering with the formation of the transcription factor IIH complex, through the degradation of the p62 subunit and sequestration of the p44 subunit. Our study results lead us to suggest that the ability of NSs to induce p62 degradation is the major contributor to its general transcription inhibition property, whereas its interaction with p44 may not play a significant role in this function. Importantly, RVFV MP-12-NSs mutant viruses with an impaired general transcription inhibition function showed a reduced cytotoxicity in cell culture and attenuated virulence in young mice

Simultaneous Detection of Rift Valley Fever, Bluetongue, Rinderpest, and Peste des Petits Ruminants Viruses by a Single-Tube Multiplex Reverse Transcriptase-PCR Assay Using a Dual-Priming Oligonucleotide System▿

PubMed Central

Yeh, Jung-Yong; Lee, Ji-Hye; Seo, Hyun-Ji; Park, Jee-Yong; Moon, Jin-San; Cho, In-Soo; Choi, In-Soo; Park, Seung-Yong; Song, Chang-Seon; Lee, Joong-Bok

2011-01-01

The aim of this study was to develop a highly sensitive and specific one-step multiplex reverse transcriptase PCR assay for the simultaneous and differential detection of Rift Valley Fever virus (RVFV), bluetongue virus (BTV), rinderpest virus (RPV), and Peste des petits ruminants virus (PPRV). These viruses cause mucosal lesions in cattle, sheep, and goats, and they are difficult to differentiate from one another based solely on their clinical presentation in suspected disease cases. In this study, we developed a multiplex reverse transcriptase PCR to detect these viruses using a novel dual-priming oligonucleotide (DPO). The DPO contains two separate priming regions joined by a polydeoxyinosine linker, which blocks extension of nonspecifically primed templates and consistently allows high PCR specificity even under less-than-optimal PCR conditions. A total of 19 DPO primers were designed to detect and discriminate between RVFV, BTV, RPV, and PPRV by the generation of 205-, 440-, 115-, and 243-bp cDNA products, respectively. The multiplex reverse transcriptase PCR described here enables the early diagnosis of these four viruses and may also be useful as part of a testing regime for cattle, sheep, or goats exhibiting similar clinical signs, including mucosal lesions. PMID:21307219

Biologically Informed Individual-based Network Model for Rift Valley Fever in the US and Evaluation of Mitigation Strategies

USDA-ARS?s Scientific Manuscript database

Rift Valley fever (RVF) is a zoonotic disease endemic in Sub-Saharan Africa with periodic outbreaks in human and animal populations. Mosquitoes are the primary disease vectors; however, Rift Valley fever virus (RVFV) can also spread by direct contact with infected tissues. The transmission cycle is ...

Characterization of Attenuated Strains of Rift Valley Fever Virus

DTIC Science & Technology

1988-01-01

confirmed as RVF virus by a plaque-reduction neutralization test (PRNT) (Earley et al., 1967) using antibody produced against ZH501. Viral replication in...original exposure. Sera were obtained from surviving hamsters and assayed for RVF virus antibody . The Reed-Muench formula (Reed & Muench, 1938) was used to... antibody production. we obtained sera from surviving hamsters that had been inoculated with the various RVF strains. Virus assays. We evaluated

Evaluation of mosquito responses to pyrethroid insecticides topically applied to sheep.

PubMed

Johnson, G D; Goosey, H B; Rolston, M G; Miller, W L; Hokit, D G; Redden, R R; Kott, R W

2013-06-01

A rise in the incidence of mosquito-transmitted Cache Valley virus (CVV) in lambs in 2011 prompted a study to evaluate on-animal pyrethroid insecticides to reduce mosquito attacks on sheep. Using enclosure traps for 1 night per wk for 6 wk, we compared engorgement rates of mosquitoes given the opportunity to feed on untreated sheep and sheep treated with 1 Python insecticide ear tag (containing 10% zeta-cypermethrin and 20% piperonyl butoxide) per animal or 2 synergized permethrin body spray treatments (containing 2.5% permethrin and 2.5% piperonyl butoxide). During the 6-wk study, 18,920 mosquitoes were collected in the animal-baited enclosure traps. Thirteen species were identified from these collections with the floodwater species Aedes increpitus and Ae. idahoensis making up 68% of the total. Potential CVV vector species, making up 25% of the samples, included Ae. vexans, Ae. dorsalis, Culex tarsalis, and Culiseta inornata. Traps baited with untreated sheep collected 9,701 mosquitoes with 65% of these engorged. Traps baited with sheep treated with Python ear tags or permethrin spray collected 4,034 and 4,555, respectively, with engorgement rates of 23% and 35%. Blood feeding on ear-tagged sheep was significantly reduced by as much as 90% compared to the untreated sheep, and protection lasted 4 wk or longer. Permethrin spray treatments were most effective within 24 h after application and provided better protection against Ae. dorsalis than the Python tag. Effectiveness of the permethrin spray diminished 1 wk after the 2nd application was made. The effect of these treatments appeared to be repellency because negligible mosquito mortality was observed at the time of collection. Further evaluation of these insecticides under conditions of natural exposure to a mosquito-borne pathogen is warranted.

Attenuation and efficacy of live-attenuated Rift Valley fever virus vaccine candidates in non-human primates.

PubMed

Smith, Darci R; Johnston, Sara C; Piper, Ashley; Botto, Miriam; Donnelly, Ginger; Shamblin, Joshua; Albariño, César G; Hensley, Lisa E; Schmaljohn, Connie; Nichol, Stuart T; Bird, Brian H

2018-05-09

Rift Valley fever virus (RVFV) is an important mosquito-borne veterinary and human pathogen that has caused large outbreaks of severe disease throughout Africa and the Arabian Peninsula. Currently, no licensed vaccine or therapeutics exists to treat this potentially deadly disease. The explosive nature of RVFV outbreaks and the severe consequences of its accidental or intentional introduction into RVFV-free areas provide the impetus for the development of novel vaccine candidates for use in both livestock and humans. Rationally designed vaccine candidates using reverse genetics have been used to develop deletion mutants of two known RVFV virulence factors, the NSs and NSm genes. These recombinant viruses were demonstrated to be protective and immunogenic in rats, mice, and sheep, without producing clinical illness in these animals. Here, we expand upon those findings and evaluate the single deletion mutant (ΔNSs rRVFV) and double deletion mutant (ΔNSs-ΔNSm rRVFV) vaccine candidates in the common marmoset (Callithrix jacchus), a non-human primate (NHP) model resembling severe human RVF disease. We demonstrate that both the ΔNSs and ΔNSs-ΔNSm rRVFV vaccine candidates were found to be safe and immunogenic in the current study. The vaccinated animals received a single dose of vaccine that led to the development of a robust antibody response. No vaccine-induced adverse reactions, signs of clinical illness or infectious virus were detected in the vaccinated marmosets. All vaccinated animals that were subsequently challenged with RVFV were protected against viremia and liver disease. In summary, our results provide the basis for further development of the ΔNSs and ΔNSs-ΔNSm rRVFV as safe and effective human RVFV vaccines for this significant public health threat.

The Rift Valley fever accessory proteins NSm and P78/NSm-GN are distinct determinants of virus propagation in vertebrate and invertebrate hosts

PubMed Central

Kreher, Felix; Tamietti, Carole; Gommet, Céline; Guillemot, Laurent; Ermonval, Myriam; Failloux, Anna-Bella; Panthier, Jean-Jacques; Bouloy, Michèle; Flamand, Marie

2014-01-01

Rift Valley fever virus (RVFV) is an enzootic virus circulating in Africa that is transmitted to its vertebrate host by a mosquito vector and causes severe clinical manifestations in humans and ruminants. RVFV has a tripartite genome of negative or ambisense polarity. The M segment contains five in-frame AUG codons that are alternatively used for the synthesis of two major structural glycoproteins, GN and GC, and at least two accessory proteins, NSm, a 14-kDa cytosolic protein, and P78/NSm-GN, a 78-kDa glycoprotein. To determine the relative contribution of P78 and NSm to RVFV infectivity, AUG codons were knocked out to generate mutant viruses expressing various sets of the M-encoded proteins. We found that, in the absence of the second AUG codon used to express NSm, a 13-kDa protein corresponding to an N-terminally truncated form of NSm, named NSm′, was synthesized from AUG 3. None of the individual accessory proteins had any significant impact on RVFV virulence in mice. However, a mutant virus lacking both NSm and NSm′ was strongly attenuated in mice and grew to reduced titers in murine macrophages, a major target cell type of RVFV. In contrast, P78 was not associated with reduced viral virulence in mice, yet it appeared as a major determinant of virus dissemination in mosquitoes. This study demonstrates how related accessory proteins differentially contribute to RVFV propagation in mammalian and arthropod hosts. PMID:26038497

A Hierarchical Network Approach for Modeling Rift Valley Fever Epidemics with Applications in North America

PubMed Central

Xue, Ling; Cohnstaedt, Lee W.; Scott, H. Morgan; Scoglio, Caterina

2013-01-01

Rift Valley fever is a vector-borne zoonotic disease which causes high morbidity and mortality in livestock. In the event Rift Valley fever virus is introduced to the United States or other non-endemic areas, understanding the potential patterns of spread and the areas at risk based on disease vectors and hosts will be vital for developing mitigation strategies. Presented here is a general network-based mathematical model of Rift Valley fever. Given a lack of empirical data on disease vector species and their vector competence, this discrete time epidemic model uses stochastic parameters following several PERT distributions to model the dynamic interactions between hosts and likely North American mosquito vectors in dispersed geographic areas. Spatial effects and climate factors are also addressed in the model. The model is applied to a large directed asymmetric network of 3,621 nodes based on actual farms to examine a hypothetical introduction to some counties of Texas, an important ranching area in the United States of America. The nodes of the networks represent livestock farms, livestock markets, and feedlots, and the links represent cattle movements and mosquito diffusion between different nodes. Cattle and mosquito (Aedes and Culex) populations are treated with different contact networks to assess virus propagation. Rift Valley fever virus spread is assessed under various initial infection conditions (infected mosquito eggs, adults or cattle). A surprising trend is fewer initial infectious organisms result in a longer delay before a larger and more prolonged outbreak. The delay is likely caused by a lack of herd immunity while the infection expands geographically before becoming an epidemic involving many dispersed farms and animals almost simultaneously. Cattle movement between farms is a large driver of virus expansion, thus quarantines can be efficient mitigation strategy to prevent further geographic spread. PMID:23667453

A hierarchical network approach for modeling Rift Valley fever epidemics with applications in North America.

PubMed

Xue, Ling; Cohnstaedt, Lee W; Scott, H Morgan; Scoglio, Caterina

2013-01-01

Rift Valley fever is a vector-borne zoonotic disease which causes high morbidity and mortality in livestock. In the event Rift Valley fever virus is introduced to the United States or other non-endemic areas, understanding the potential patterns of spread and the areas at risk based on disease vectors and hosts will be vital for developing mitigation strategies. Presented here is a general network-based mathematical model of Rift Valley fever. Given a lack of empirical data on disease vector species and their vector competence, this discrete time epidemic model uses stochastic parameters following several PERT distributions to model the dynamic interactions between hosts and likely North American mosquito vectors in dispersed geographic areas. Spatial effects and climate factors are also addressed in the model. The model is applied to a large directed asymmetric network of 3,621 nodes based on actual farms to examine a hypothetical introduction to some counties of Texas, an important ranching area in the United States of America. The nodes of the networks represent livestock farms, livestock markets, and feedlots, and the links represent cattle movements and mosquito diffusion between different nodes. Cattle and mosquito (Aedes and Culex) populations are treated with different contact networks to assess virus propagation. Rift Valley fever virus spread is assessed under various initial infection conditions (infected mosquito eggs, adults or cattle). A surprising trend is fewer initial infectious organisms result in a longer delay before a larger and more prolonged outbreak. The delay is likely caused by a lack of herd immunity while the infection expands geographically before becoming an epidemic involving many dispersed farms and animals almost simultaneously. Cattle movement between farms is a large driver of virus expansion, thus quarantines can be efficient mitigation strategy to prevent further geographic spread.

Comparison of Rift Valley fever virus replication in North American livestock and wildlife cell lines.

PubMed

Gaudreault, Natasha N; Indran, Sabarish V; Bryant, P K; Richt, Juergen A; Wilson, William C

2015-01-01

Rift Valley fever virus (RVFV) causes disease outbreaks across Africa and the Arabian Peninsula, resulting in high morbidity and mortality among young domestic livestock, frequent abortions in pregnant animals, and potentially severe or fatal disease in humans. The possibility of RVFV spreading to the United States or other countries worldwide is of significant concern to animal and public health, livestock production, and trade. The mechanism for persistence of RVFV during inter-epidemic periods may be through mosquito transovarial transmission and/or by means of a wildlife reservoir. Field investigations in endemic areas and previous in vivo studies have demonstrated that RVFV can infect a wide range of animals, including indigenous wild ruminants of Africa. Yet no predominant wildlife reservoir has been identified, and gaps in our knowledge of RVFV permissive hosts still remain. In North America, domestic goats, sheep, and cattle are susceptible hosts for RVFV and several competent vectors exist. Wild ruminants such as deer might serve as a virus reservoir and given their abundance, wide distribution, and overlap with livestock farms and human populated areas could represent an important risk factor. The objective of this study was to assess a variety of cell lines derived from North American livestock and wildlife for susceptibility and permissiveness to RVFV. Results of this study suggest that RVFV could potentially replicate in native deer species such as white-tailed deer, and possibly a wide range of non-ruminant animals. This work serves to guide and support future animal model studies and risk model assessment regarding this high-consequence zoonotic pathogen.

The Diagnosis and application of a convective vorticity vector associated with convective systems

NASA Astrophysics Data System (ADS)

Gao, S.; Zhou, Y.; Tao, W.

2005-05-01

Although dry/moist potential vorticity is a very useful and powerful physical quantity in the large scale dynamics, it is not a quite ideal dynamical tool for the study of convective systems or severe storms. A new convective vorticity vector (CVV) is introduced in this study to identify the development of convective systems or severe storms. The daily Aviation (AVN) Model Data is used to diagnose the distribution of the CVV associated with rain storms occurred in the period of Meiyu in 1998. The results have clearly demonstrated that the CVV is an effective vector for indicating the convective actions along the Meiyu front. The CVV also is used to diagnose a 2-D cloud-resolving simulation data associated with 2-D tropical convection. The cloud model is forced by the vertical velocity, zonal wind, horizontal advection, and sea surface temperature obtained from the Tropical cean-Global tmosphere (TOGA) Coupled Ocean-Atmosphere Response Experiment (COARE) and is integrated for a selected 10-day period. The CVV has zonal and vertical components in the 2-D x-z frame. Analysis of zonally averaged and mass-integrated quantities shows that the correlation coefficient between the vertical component of the CVV and the sum of the cloud hydrometeor mixing ratios is 0.81, whereas the correlation coefficient between the zonal component and the sum of the mixing ratios is only 0.18. This indicates that the vertical component of the CVV is closely associated with tropical convection. The tendency equation for the vertical component of the CVV is derived and the zonally averaged and mass-integrated tendency budgets are analyzed. The tendency of the vertical component of the CVV is determined by the interaction between the vorticity and the zonal gradient of cloud heating. The results demonstrate that the vertical component of the CVV is a cloud-linked parameter and can be used to study tropical convection.

Evaluation of Fluorescence Microsphere Immunoassay for the Detection of Antibodies to Rift Valley Fever Nucleocapsid Protein and Glycoproteins

USDA-ARS?s Scientific Manuscript database

Rift Valley Fever virus (RVFV) is a zoonotic virus that infects ruminants including cattle, sheep, goats, camels and buffalo. Multiplexing diagnostic assays that can simultaneously detect antibodies against multiple RVFV antigens offer a high throughput test for disease surveillance and vaccine eva...

Post-exposure vaccination with MP-12 lacking NSs protects mice against lethal Rift Valley fever virus challenge.

PubMed

Gowen, Brian B; Bailey, Kevin W; Scharton, Dionna; Vest, Zachery; Westover, Jonna B; Skirpstunas, Ramona; Ikegami, Tetsuro

2013-05-01

Rift Valley fever virus (RVFV) causes severe disease in humans and livestock. There are currently no approved antivirals or vaccines for the treatment or prevention of RVF disease in humans. A major virulence factor of RVFV is the NSs protein, which inhibits host transcription including the interferon (IFN)-β gene and promotes the degradation of dsRNA-dependent protein kinase, PKR. We analyzed the efficacy of the live-attenuated MP-12 vaccine strain and MP-12 variants that lack the NSs protein as post-exposure vaccinations. Although parental MP-12 failed to elicit a protective effect in mice challenged with wild-type (wt) RVFV by the intranasal route, significant protection was demonstrated by vaccination with MP-12 strains lacking NSs when they were administered at 20-30 min post-exposure. Viremia and virus replication in liver, spleen and brain were also inhibited by post-exposure vaccination with MP-12 lacking NSs. The protective effect was mostly lost when vaccination was delayed 6 or 24 h after intranasal RVFV challenge. When mice were challenged subcutaneously, efficacy of MP-12 lacking NSs was diminished, most likely due to more rapid dissemination of wt RVFV. Our findings suggest that post-exposure vaccination with MP-12 lacking NSs may be developed as a novel post-exposure treatment to prevent RVF. Copyright © 2013 Elsevier B.V. All rights reserved.

Seroprevalence of Alkhurma and other hemorrhagic fever viruses, Saudi Arabia.

PubMed

Memish, Ziad A; Albarrak, Ali; Almazroa, Mohammad A; Al-Omar, Ibrahim; Alhakeem, Rafat; Assiri, Abdullah; Fagbo, Shamsudeen; MacNeil, Adam; Rollin, Pierre E; Abdullah, Nageeb; Stephens, Gwen

2011-12-01

A 2009 deployment of military units from several Saudi Arabian provinces to Jazan Province, Saudi Arabia, enabled us to evaluate exposure to Alkhurma, Crimean-Congo, dengue, and Rift Valley hemorrhagic fever viruses. Seroprevalence to all viruses was low; however, Alkhurma virus seroprevalence was higher (1.3%) and less geographically restricted than previously thought.

The First Prediction of a Rift Valley Fever Outbreak

NASA Technical Reports Server (NTRS)

Anyamba, Assaf; Chretien, Jean-Paul; Small, Jennifer; Tucker, Compton J.; Formenty, Pierre; Richardson, Jason H.; Britch, Seth C.; Schnabel, David C.; Erickson, Ralph L.; Linthicum, Kenneth J.

2009-01-01

El Nino/Southern Oscillation (ENSO) related anomalies were analyzed using a combination of satellite measurements of elevated sea surface temperatures, and subsequent elevated rainfall and satellite derived normalized difference vegetation index data. A Rift Valley fever risk mapping model using these climate data predicted areas where outbreaks of Rift Valley fever in humans and animals were expected and occurred in the Horn of Africa from December 2006 to May 2007. The predictions were subsequently confirmed by entomological and epidemiological field investigations of virus activity in the areas identified as at risk. Accurate spatial and temporal predictions of disease activity, as it occurred first in southern Somalia and then through much of Kenya before affecting northern Tanzania, provided a 2 to 6 week period of warning for the Horn of Africa that facilitated disease outbreak response and mitigation activities. This is the first prospective prediction of a Rift Valley fever outbreak.

Potential Effects of Rift Valley Fever in the United States

USDA-ARS?s Scientific Manuscript database

Rift Valley fever virus (RVFV) has been the cause of disease outbreaks throughout Africa and the Arabian Peninsula, and the infection often results in heavy economic costs through loss of livestock. If RVFV, which is common to select agent lists of the US Department of Health and Human Services and ...

Biochemical and biophysical characterization of cell-free synthesized Rift Valley fever virus nucleoprotein capsids enables in vitro screening to identify novel antivirals.

PubMed

Broce, Sean; Hensley, Lisa; Sato, Tomoharu; Lehrer-Graiwer, Joshua; Essrich, Christian; Edwards, Katie J; Pajda, Jacqueline; Davis, Christopher J; Bhadresh, Rami; Hurt, Clarence R; Freeman, Beverly; Lingappa, Vishwanath R; Kelleher, Colm A; Karpuj, Marcela V

2016-05-14

Viral capsid assembly involves the oligomerization of the capsid nucleoprotein (NP), which is an essential step in viral replication and may represent a potential antiviral target. An in vitro transcription-translation reaction using a wheat germ (WG) extract in combination with a sandwich ELISA assay has recently been used to identify small molecules with antiviral activity against the rabies virus. Here, we examined the application of this system to viruses with capsids with a different structure, such as the Rift Valley fever virus (RVFV), the etiological agent of a severe emerging infectious disease. The biochemical and immunological characterization of the in vitro-generated RVFV NP assembly products enabled the distinction between intermediately and highly ordered capsid structures. This distinction was used to establish a screening method for the identification of potential antiviral drugs for RVFV countermeasures. These results indicated that this unique analytical system, which combines nucleoprotein oligomerization with the specific immune recognition of a highly ordered capsid structure, can be extended to various viral families and used both to study the early stages of NP assembly and to assist in the identification of potential antiviral drugs in a cost-efficient manner. Reviewed by Jeffry Skolnick and Noah Isakov. For the full reviews please go to the Reviewers' comments section.

Dual functions of Rift Valley fever virus NSs protein: inhibition of host mRNA transcription and post-transcriptional downregulation of protein kinase PKR.

PubMed

Ikegami, Tetsuro; Narayanan, Krishna; Won, Sungyong; Kamitani, Wataru; Peters, C J; Makino, Shinji

2009-09-01

Rift Valley fever virus (RVFV), which belongs to the genus Phlebovirus, family Bunyaviridae, is a negative-stranded RNA virus carrying a single-stranded, tripartite RNA genome. RVFV is an important zoonotic pathogen transmitted by mosquitoes and causes large outbreaks among ruminants and humans in Africa and the Arabian Peninsula. Human patients develop an acute febrile illness, followed by a fatal hemorrhagic fever, encephalitis, or ocular diseases. A viral nonstructural protein, NSs, is a major viral virulence factor. Past studies showed that NSs suppresses the transcription of host mRNAs, including interferon-beta mRNAs. Here we demonstrated that the NSs protein induced post-transcriptional downregulation of dsRNA-dependent protein kinase (PKR), to prevent phosphorylation of eIF2alpha and promoted viral translation in infected cells. These two biological activities of the NSs most probably have a synergistic effect in suppressing host innate immune functions and facilitate efficient viral replication in infected mammalian hosts.

Dual Functions of Rift Valley Fever Virus NSs Protein: Inhibition of Host mRNA Transcription and Post-transcriptional Downregulation of Protein Kinase PKR

PubMed Central

Ikegami, Tetsuro; Narayanan, Krishna; Won, Sungyong; Kamitani, Wataru; Peters, C. J.; Makino, Shinji

2011-01-01

Rift Valley fever virus (RVFV), which belongs to the genus Phlebovirus, family Bunyaviridae, is a negative-stranded RNA virus carrying a single-stranded, tripartite RNA genome. RVFV is an important zoonotic pathogen transmitted by mosquitoes and causes large outbreaks among ruminants and humans in Africa and the Arabian Peninsula. Human patients develop an acute febrile illness, followed by a fatal hemorrhagic fever, encephalitis or ocular diseases. A viral nonstructural protein, NSs, is a major viral virulence factor. Past studies showed that NSs suppresses the transcription of host mRNAs, including interferon-β mRNAs. Here we demonstrated that the NSs protein induced post-transcriptional downregulation of dsRNA-dependent protein kinase, PKR, to prevent phosphorylation of eIF2α and promoted viral translation in infected cells. These two biological activities of the NSs most probably have a synergistic effect in suppressing host innate immune functions and facilitate efficient viral replication in infected mammalian hosts. PMID:19751406

Phylogeographic Reconstructions of a Rift Valley Fever Virus Strain Reveals Transboundary Animal Movements from Eastern Continental Africa to the Union of the Comoros.

PubMed

Maquart, M; Pascalis, H; Abdouroihamane, S; Roger, M; Abdourahime, F; Cardinale, E; Cêtre-Sossah, C

2016-04-01

Major explosive outbreaks of Rift Valley fever (RVF), an arthropod borne zoonotic disease, occur in humans and animals with significant mortality and economic impact across continental Africa and the Indian Ocean region (Madagascar, the Comoros archipelago). Recently, sporadic human cases have been reported in Mayotte and Grande Comore, two islands belonging to the Comoros archipelago. To identify the hypothetical source of virus introduction in an inter-epidemic or a post-epidemic period, a longitudinal survey of livestock was set up in Comorian ruminant populations, known to be susceptible hosts. The phylogeographic genomic analysis has shown that RVF virus (RVFV) detected in a zebu collected in Anjouan in August 2011 seems to be related to the last known epidemic of RVF which occurred in East Africa and Madagascar (2007-2009). This result highlights the fact that RVFV is maintained within local livestock populations and transboundary animal movements from eastern continental Africa to Indian Ocean islands likely result in RVFV crossover. © 2014 Blackwell Verlag GmbH.

A novel indirect ELISA based on glycoprotein Gn for the detection of IgG antibodies against Rift Valley fever virus in small ruminants.

PubMed

Jäckel, S; Eiden, M; Balkema-Buschmann, A; Ziller, M; van Vuren, P Jansen; Paweska, J T; Groschup, M H

2013-10-01

Rift Valley fever virus (RVFV) is an emerging zoonotic pathogen that causes high morbidity and mortality in humans and livestock. In this paper, we describe the cloning, expression and purification of RVFV glycoprotein Gn and its application as a diagnostic antigen in an indirect ELISA for the specific detection of RVF IgG antibodies in sheep and goats. The performance of this Gn based ELISA is validated using a panel of almost 2000 field samples from sheep and goats from Mozambique, Senegal, Uganda and Yemen. All serum samples were also tested by virus neutralization test (VNT), the gold standard method for RVFV serological testing. Compared to the VNT results the Gn based ELISA proved to have an excellent sensitivity (94.56%) and specificity (95.57%). Apart from establishing this new diagnostic assay, these results also demonstrate a close correlation between the presence of RVFV Gn and neutralizing antibodies. Copyright © 2013 Elsevier Ltd. All rights reserved.

Seroprevalence of Sheep and Goat Pox, Peste Des Petits Ruminants and Rift Valley Fever in Saudi Arabia.

PubMed

Boshra, Hani; Truong, Thang; Babiuk, Shawn; Hemida, Maged Gomaa

2015-01-01

Sheep and goat pox, peste des petits ruminants and Rift Valley fever are important diseases of small ruminant livestock. Sheep and goat pox, along with peste des petits ruminants, are endemic throughout most of Africa, Asia and the Middle East. Whereas Rift Valley fever is endemic in Africa, outbreaks in the Middle East have been reported over the past decade, including the Arabian Peninsula. Saudi Arabia is a major importer of livestock, and understanding the prevalence of these viral infections would be useful for disease control. In this study, sera from sheep and goats were collected from 3 regions in Saudi Arabia. They were evaluated for antibodies specific to sheep and goat pox, peste des petits ruminants and Rift Valley fever by virus neutralization assays. To the best of our knowledge, this is the first study to evaluate the seroprevalence of these viruses in sheep and goats.

Impact of Global Climate on Rift Valley Fever Disease Outbreaks

USDA-ARS?s Scientific Manuscript database

Rift Valley fever is a viral disease of animals and humans in Africa and the Middle East that is transmitted by mosquitoes. Since the virus was first isolated in Kenya in 1930 it has caused significant impact to animal and human health and national economies, and it is of concern to the internationa...

Rift Valley Fever Vaccine Virus Clone 13 Is Able to Cross the Ovine Placental Barrier Associated with Foetal Infections, Malformations, and Stillbirths.

PubMed

Makoschey, Birgit; van Kilsdonk, Emma; Hubers, Willem R; Vrijenhoek, Mieke P; Smit, Marianne; Wichgers Schreur, Paul J; Kortekaas, Jeroen; Moulin, Véronique

2016-03-01

Rift Valley fever virus (RVFV) is a mosquito-borne pathogen that affects domesticated ruminants and occasionally humans. Classical RVF vaccines are based on formalin-inactivated virus or the live-attenuated Smithburn strain. The inactivated vaccine is highly safe but requires multiple administrations and yearly re-vaccinations. Although the Smithburn vaccine provides solid protection after a single vaccination, this vaccine is not safe for pregnant animals. An alternative live-attenuated vaccine, named Clone 13, carries a large natural deletion in the NSs gene which encodes the major virulence factor of the virus. The Clone 13 vaccine was previously shown to be safe for young lambs and calves. Moreover, a study in pregnant ewes suggested that the vaccine could also be applied safely during gestation. To anticipate on a possible future incursion of RVFV in Europe, we have evaluated the safety of Clone 13 for young lambs and pregnant ewes. In line with the guidelines from the World Organisation for Animal health (Office International des Epizooties, OIE) and regulations of the European Pharmacopeia (EP), these studies were performed with an overdose. Our studies with lambs showed that Clone 13 dissemination within vaccinated animals is very limited. Moreover, the Clone 13 vaccine virus was not shed nor spread to in-contact sentinels and did not revert to virulence upon animal-to-animal passage. Importantly, a large experiment with pregnant ewes demonstrated that the Clone 13 virus is able to spread to the fetus, resulting in malformations and stillbirths. Altogether, our results suggest that Clone 13 can be applied safely in lambs, but that caution should be taken when Clone 13 is used in pregnant animals, particularly during the first trimester of gestation.

A Convective Vorticity Vector Associated With Tropical Convection: A 2D Cloud-Resolving Modeling Study

NASA Technical Reports Server (NTRS)

Gao, Shou-Ting; Ping, Fan; Li, Xiao-Fan; Tao, Wei-Kuo

2004-01-01

Although dry/moist potential vorticity is a useful physical quantity for meteorological analysis, it cannot be applied to the analysis of 2D simulations. A convective vorticity vector (CVV) is introduced in this study to analyze 2D cloud-resolving simulation data associated with 2D tropical convection. The cloud model is forced by the vertical velocity, zonal wind, horizontal advection, and sea surface temperature obtained from the TOGA COARE, and is integrated for a selected 10-day period. The CVV has zonal and vertical components in the 2D x-z frame. Analysis of zonally-averaged and mass-integrated quantities shows that the correlation coefficient between the vertical component of the CVV and the sum of the cloud hydrometeor mixing ratios is 0.81, whereas the correlation coefficient between the zonal component and the sum of the mixing ratios is only 0.18. This indicates that the vertical component of the CVV is closely associated with tropical convection. The tendency equation for the vertical component of the CVV is derived and the zonally-averaged and mass-integrated tendency budgets are analyzed. The tendency of the vertical component of the CVV is determined by the interaction between the vorticity and the zonal gradient of cloud heating. The results demonstrate that the vertical component of the CVV is a cloud-linked parameter and can be used to study tropical convection.

The L, M, and S Segments of Rift Valley Fever Virus MP-12 Vaccine Independently Contribute to a Temperature-Sensitive Phenotype

PubMed Central

Nishiyama, Shoko; Lokugamage, Nandadeva

2016-01-01

ABSTRACT Rift Valley fever (RVF) is endemic to Africa, and the mosquito-borne disease is characterized by “abortion storms” in ruminants and by hemorrhagic fever, encephalitis, and blindness in humans. Rift Valley fever virus (RVFV; family Bunyaviridae, genus Phlebovirus) has a tripartite negative-stranded RNA genome (L, M, and S segments). A live-attenuated vaccine for RVF, the MP-12 vaccine, is conditionally licensed for veterinary use in the United States. MP-12 is fully attenuated by the combination of the partially attenuated L, M, and S segments. Temperature sensitivity (ts) limits viral replication at a restrictive temperature and may be involved with viral attenuation. In this study, we aimed to characterize the ts mutations for MP-12. The MP-12 vaccine showed restricted replication at 38°C and replication shutoff (100-fold or greater reduction in virus titer compared to that at 37°C) at 39°C in Vero and MRC-5 cells. Using rZH501 reassortants with either the MP-12 L, M, or S segment, we found that all three segments encode a temperature-sensitive phenotype. However, the ts phenotype of the S segment was weaker than that of the M or L segment. We identified Gn-Y259H, Gc-R1182G, L-V172A, and L-M1244I as major ts mutations for MP-12. The ts mutations in the L segment decreased viral RNA synthesis, while those in the M segment delayed progeny production from infected cells. We also found that a lack of NSs and/or 78kD/NSm protein expression minimally affected the ts phenotype. Our study revealed that MP-12 is a unique vaccine carrying ts mutations in the L, M, and S segments. IMPORTANCE Rift Valley fever (RVF) is a mosquito-borne viral disease endemic to Africa, characterized by high rates of abortion in ruminants and severe diseases in humans. Vaccination is important to prevent the spread of disease, and a live-attenuated MP-12 vaccine is currently the only vaccine with a conditional license in the United States. This study determined the temperature

The L, M, and S Segments of Rift Valley Fever Virus MP-12 Vaccine Independently Contribute to a Temperature-Sensitive Phenotype.

PubMed

Nishiyama, Shoko; Lokugamage, Nandadeva; Ikegami, Tetsuro

2016-01-27

Rift Valley fever (RVF) is endemic to Africa, and the mosquito-borne disease is characterized by "abortion storms" in ruminants and by hemorrhagic fever, encephalitis, and blindness in humans. Rift Valley fever virus (RVFV; family Bunyaviridae, genus Phlebovirus) has a tripartite negative-stranded RNA genome (L, M, and S segments). A live-attenuated vaccine for RVF, the MP-12 vaccine, is conditionally licensed for veterinary use in the United States. MP-12 is fully attenuated by the combination of the partially attenuated L, M, and S segments. Temperature sensitivity (ts) limits viral replication at a restrictive temperature and may be involved with viral attenuation. In this study, we aimed to characterize the ts mutations for MP-12. The MP-12 vaccine showed restricted replication at 38°C and replication shutoff (100-fold or greater reduction in virus titer compared to that at 37°C) at 39°C in Vero and MRC-5 cells. Using rZH501 reassortants with either the MP-12 L, M, or S segment, we found that all three segments encode a temperature-sensitive phenotype. However, the ts phenotype of the S segment was weaker than that of the M or L segment. We identified Gn-Y259H, Gc-R1182G, L-V172A, and L-M1244I as major ts mutations for MP-12. The ts mutations in the L segment decreased viral RNA synthesis, while those in the M segment delayed progeny production from infected cells. We also found that a lack of NSs and/or 78kD/NSm protein expression minimally affected the ts phenotype. Our study revealed that MP-12 is a unique vaccine carrying ts mutations in the L, M, and S segments. Rift Valley fever (RVF) is a mosquito-borne viral disease endemic to Africa, characterized by high rates of abortion in ruminants and severe diseases in humans. Vaccination is important to prevent the spread of disease, and a live-attenuated MP-12 vaccine is currently the only vaccine with a conditional license in the United States. This study determined the temperature sensitivity (ts) of MP-12

Development of a novel real-time RT-PCR assay to detect Seneca Valley virus-1 associated with emerging cases of vesicular disease in pigs.

PubMed

Fowler, Veronica L; Ransburgh, Russell H; Poulsen, Elizabeth G; Wadsworth, Jemma; King, Donald P; Mioulet, Valerie; Knowles, Nick J; Williamson, Susanna; Liu, Xuming; Anderson, Gary A; Fang, Ying; Bai, Jianfa

2017-01-01

Seneca Valley virus 1 (SVV-1) can cause vesicular disease that is clinically indistinguishable from foot-and-mouth disease, vesicular stomatitis and swine vesicular disease. SVV-1-associated disease has been identified in pigs in several countries, namely USA, Canada, Brazil and China. Diagnostic tests are required to reliably detect this emerging virus, and this report describes the development and evaluation of a novel real-time (r) reverse-transcription (RT) PCR assay (rRT-PCR), targeting the viral polymerase gene (3D) of SVV-1. This new assay detected all historical and contemporary SVV-1 isolates examined (n=8), while no cross-reactivity was observed with nucleic acid templates prepared from other vesicular disease viruses or common swine pathogens. The analytical sensitivity of the rRT-PCR was 0.79 TCID 50 /ml and the limit of detection was equivalent using two different rRT-PCR master-mixes. The performance of the test was further evaluated using pig nasal (n=25) and rectal swab samples (n=25), where concordant results compared to virus sequencing were generated for 43/50 samples. The availability of this assay, will enable laboratories to rapidly detect SVV-1 in cases of vesicular disease in pigs, negated for notifiable diseases, and could enable existing knowledge gaps to be investigated surrounding the natural epidemiology of SVV-1. Copyright © 2016 Elsevier B.V. All rights reserved.

Blood Meal Analysis of Mosquitoes Involved in a Rift Valley fever Outbreak

USDA-ARS?s Scientific Manuscript database

Background: Rift Valley fever (RVF) is a zoonosis of domestic ruminants in Africa. Bloodfed mosquitoes collected during the 2006-2007 RVF outbreak in Kenya were analyzed to determine the virus infection status and animal source of the bloodmeals. Bloodmeals from individual mosquito abdomens were sc...

Variable versus conventional lung protective mechanical ventilation during open abdominal surgery (PROVAR): a randomised controlled trial.

PubMed

Spieth, P M; Güldner, A; Uhlig, C; Bluth, T; Kiss, T; Conrad, C; Bischlager, K; Braune, A; Huhle, R; Insorsi, A; Tarantino, F; Ball, L; Schultz, M J; Abolmaali, N; Koch, T; Pelosi, P; Gama de Abreu, M

2018-03-01

Experimental studies showed that controlled variable ventilation (CVV) yielded better pulmonary function compared to non-variable ventilation (CNV) in injured lungs. We hypothesized that CVV improves intraoperative and postoperative respiratory function in patients undergoing open abdominal surgery. Fifty patients planned for open abdominal surgery lasting >3 h were randomly assigned to receive either CVV or CNV. Mean tidal volumes and PEEP were set at 8 ml kg -1 (predicted body weight) and 5 cm H 2 O, respectively. In CVV, tidal volumes varied randomly, following a normal distribution, on a breath-by-breath basis. The primary endpoint was the forced vital capacity (FVC) on postoperative Day 1. Secondary endpoints were oxygenation, non-aerated lung volume, distribution of ventilation, and pulmonary and extrapulmonary complications until postoperative Day 5. FVC did not differ significantly between CVV and CNV on postoperative Day 1, 61.5 (standard deviation 22.1) % vs 61.9 (23.6) %, respectively; mean [95% confidence interval (CI)] difference, -0.4 (-13.2-14.0), P=0.95. Intraoperatively, CVV did not result in improved respiratory function, haemodynamics, or redistribution of ventilation compared to CNV. Postoperatively, FVC, forced expiratory volume at the first second (FEV 1 ), and FEV 1 /FVC deteriorated, while atelectasis volume and plasma levels of interleukin-6 and interleukin-8 increased, but values did not differ between groups. The incidence of postoperative pulmonary and extrapulmonary complications was comparable in CVV and CNV. In patients undergoing open abdominal surgery, CVV did not improve intraoperative and postoperative respiratory function compared with CNV. NCT 01683578. Copyright © 2017 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

Comparative Analysis of Native Crocus Taxa as a Great Source of Flavonoids with High Antioxidant Activity.

PubMed

Šola, Ivana; Stipaničev, Mirta; Vujčić, Valerija; Mitić, Božena; Huđek, Ana; Rusak, Gordana

2018-06-02

Native Crocus taxa are abundant in regions with moderate and dry climate; however, their potential in the food industry has thus far been neglected. The objective of this study was to compare the quantitative and qualitative flavonoid content and antioxidant and cytotoxic activity in organs of several populations of Croatian native taxa and assess their potential for application in the food industry. The dominant flavonoids in the native Crocus taxa were kaempferol and quercetin. Tepals contained similar or higher concentrations of flavonoid-glycosides than other organs. Tepals from Cvv1 and Cvv2 populations contained more flavonoid-glycosides than the commonly used spice saffron (C. sativus stigmas). The FRAP antioxidant activity of Cvv1 and Cvv5 tepals was similar to that of standard Trolox. DPPH inhibition of Cvv1 and Cvv3 tepals was within the range of that recorded for saffron. Cvv1 tepals significantly reduced reactive oxygen species in the broadest concentration range (50-1000 μg/ml), and showed considerable antioxidant activity in the ABTS assay, equal to 82% of standard Trolox antioxidant activity. A significantly higher concentration of kaempferol-rutinoside was recorded in this than in other taxa. The flavonoid showed a very strong or strong correlation with antioxidant assays results, and a negative correlation with cellular reactive oxygen species concentration. We therefore presumed that kaempferol-rutinoside is one of the main antioxidant phenolics in Crocus tepals. None of the tested extracts showed cytotoxicity toward Caco-2 cells. The results revealed that Cvv tepals have potential as a food supplement and are a promising material for further food safety tests.

Evidence for enzootic circulation of Rift Valley fever virus among livestock in Cameroon.

PubMed

Rissmann, M; Eiden, M; Wade, A; Poueme, R; Abdoulkadiri, S; Unger, H; Ziegler, U; Homeier, T; Groschup, M H

2017-08-01

Rift Valley fever virus (RVFV) is an arthropod-borne pathogen, causing serious epidemics in Africa and the Arabian Peninsula. In Cameroon serological data indicate the presence of RVFV, but active circulation of RVFV, causing clinical infections has not been proven yet. For this purpose we carried out a serological and molecular study on a total of 1953 randomly selected serum samples of small ruminants and cattle, which were collected in years 2013 and 2014 in Cameroon. In a first step, sera were screened serologically using a variety of assay formats to reveal RVFV specific antibodies. At the second stage, seropositive specimen were assessed for acute RVFV infections via IgM-specific ELISA and quantitative real-time RT-PCR. Our data show a significant difference in the antibody prevalence in cattle (13.5% [95% confidence interval: 11.4-15.7]) and small ruminants (3.4% [95% confidence interval: 2.3-4.7]), with indications for annual fluctuations and significant regional differences of seropositivity. One small ruminant and three bovines were eventually found to be positive in IgM ELISA and indications for viremia were found in one bovine by RVFV genome detection using quantitative real-time RT-PCR. The results of this study therefore corroborate the presence of acute RVFV-infection and its circulation in Cameroon. Copyright © 2017 Elsevier B.V. All rights reserved.

The Use of NanoTrap Particles as a Sample Enrichment Method to Enhance the Detection of Rift Valley Fever Virus

PubMed Central

Shafagati, Nazly; Narayanan, Aarthi; Baer, Alan; Fite, Katherine; Pinkham, Chelsea; Bailey, Charles; Kashanchi, Fatah; Lepene, Benjamin; Kehn-Hall, Kylene

2013-01-01

Background Rift Valley Fever Virus (RVFV) is a zoonotic virus that is not only an emerging pathogen but is also considered a biodefense pathogen due to the threat it may cause to public health and national security. The current state of diagnosis has led to misdiagnosis early on in infection. Here we describe the use of a novel sample preparation technology, NanoTrap particles, to enhance the detection of RVFV. Previous studies demonstrated that NanoTrap particles lead to both 100 percent capture of protein analytes as well as an improvement of more than 100-fold in sensitivity compared to existing methods. Here we extend these findings by demonstrating the capture and enrichment of viruses. Results Screening of NanoTrap particles indicated that one particle, NT53, was the most efficient at RVFV capture as demonstrated by both qRT-PCR and plaque assays. Importantly, NT53 capture of RVFV resulted in greater than 100-fold enrichment from low viral titers when other diagnostics assays may produce false negatives. NT53 was also capable of capturing and enhancing RVFV detection from serum samples. RVFV that was inactivated through either detergent or heat treatment was still found bound to NT53, indicating the ability to use NanoTrap particles for viral capture prior to transport to a BSL-2 environment. Furthermore, both NP-40-lysed virus and purified RVFV RNA were bound by NT53. Importantly, NT53 protected viral RNA from RNase A degradation, which was not observed with other commercially available beads. Incubation of RVFV samples with NT53 also resulted in increased viral stability as demonstrated through preservation of infectivity at elevated temperatures. Finally, NanoTrap particles were capable of capturing VEEV and HIV, demonstrating the broad applicability of NanoTrap particles for viral diagnostics. Conclusion This study demonstrates NanoTrap particles are capable of capturing, enriching, and protecting RVFV virions. Furthermore, the use of NanoTrap particles

A Genome-Wide RNA Interference Screen Identifies a Role for Wnt/β-Catenin Signaling during Rift Valley Fever Virus Infection.

PubMed

Harmon, Brooke; Bird, Sara W; Schudel, Benjamin R; Hatch, Anson V; Rasley, Amy; Negrete, Oscar A

2016-08-15

Rift Valley fever virus (RVFV) is an arbovirus within the Bunyaviridae family capable of causing serious morbidity and mortality in humans and livestock. To identify host factors involved in bunyavirus replication, we employed genome-wide RNA interference (RNAi) screening and identified 381 genes whose knockdown reduced infection. The Wnt pathway was the most represented pathway when gene hits were functionally clustered. With further investigation, we found that RVFV infection activated Wnt signaling, was enhanced when Wnt signaling was preactivated, was reduced with knockdown of β-catenin, and was blocked using Wnt signaling inhibitors. Similar results were found using distantly related bunyaviruses La Crosse virus and California encephalitis virus, suggesting a conserved role for Wnt signaling in bunyaviral infection. We propose a model where bunyaviruses activate Wnt-responsive genes to regulate optimal cell cycle conditions needed to promote efficient viral replication. The findings in this study should aid in the design of efficacious host-directed antiviral therapeutics. RVFV is a mosquito-borne bunyavirus that is endemic to Africa but has demonstrated a capacity for emergence in new territories (e.g., the Arabian Peninsula). As a zoonotic pathogen that primarily affects livestock, RVFV can also cause lethal hemorrhagic fever and encephalitis in humans. Currently, there are no treatments or fully licensed vaccines for this virus. Using high-throughput RNAi screening, we identified canonical Wnt signaling as an important host pathway regulating RVFV infection. The beneficial role of Wnt signaling was observed for RVFV, along with other disparate bunyaviruses, indicating a conserved bunyaviral replication mechanism involving Wnt signaling. These studies supplement our knowledge of the fundamental mechanisms of bunyavirus infection and provide new avenues for countermeasure development against pathogenic bunyaviruses. Copyright © 2016 Harmon et al.

A genome-wide RNA interference screen identifies a role for Wnt/β-catenin signaling during Rift Valley Fever Virus infection

DOE PAGES

Harmon, Brooke; Bird, Sara W.; Schudel, Benjamin R.; ...

2016-05-25

Rift Valley fever virus (RVFV) is an arbovirus within the Bunyaviridae family capable of causing serious morbidity and mortality in humans and livestock. To identify host factors involved in bunyavirus replication, we employed genome-wide RNA interference (RNAi) screening and identified 381 genes whose knockdown reduced infection. The Wnt pathway was the most represented pathway when gene hits were functionally clustered. With further investigation, we found that RVFV infection activated Wnt signaling, was enhanced when Wnt signaling was preactivated, was reduced with knockdown of β-catenin, and was blocked using Wnt signaling inhibitors. Similar results were found using distantly related bunyaviruses Lamore » Crosse virus and California encephalitis virus, suggesting a conserved role for Wnt signaling in bunyaviral infection. We propose a model where bunyaviruses activate Wnt-responsive genes to regulate optimal cell cycle conditions needed to promote efficient viral replication. The findings in this study should aid in the design of efficacious host-directed antiviral therapeutics. IMPORTANCE RVFV is a mosquito-borne bunyavirus that is endemic to Africa but has demonstrated a capacity for emergence in new territories (e.g., the Arabian Peninsula). As a zoonotic pathogen that primarily affects livestock, RVFV can also cause lethal hemorrhagic fever and encephalitis in humans. Currently, there are no treatments or fully licensed vaccines for this virus. Using high-throughput RNAi screening, we identified canonical Wnt signaling as an important host pathway regulating RVFV infection. The beneficial role of Wnt signaling was observed for RVFV, along with other disparate bunyaviruses, indicating a conserved bunyaviral replication mechanism involving Wnt signaling. Lastly, these studies supplement our knowledge of the fundamental mechanisms of bunyavirus infection and provide new avenues for countermeasure development against pathogenic bunyaviruses.« less

A genome-wide RNA interference screen identifies a role for Wnt/β-catenin signaling during Rift Valley Fever Virus infection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harmon, Brooke; Bird, Sara W.; Schudel, Benjamin R.

Rift Valley fever virus (RVFV) is an arbovirus within the Bunyaviridae family capable of causing serious morbidity and mortality in humans and livestock. To identify host factors involved in bunyavirus replication, we employed genome-wide RNA interference (RNAi) screening and identified 381 genes whose knockdown reduced infection. The Wnt pathway was the most represented pathway when gene hits were functionally clustered. With further investigation, we found that RVFV infection activated Wnt signaling, was enhanced when Wnt signaling was preactivated, was reduced with knockdown of β-catenin, and was blocked using Wnt signaling inhibitors. Similar results were found using distantly related bunyaviruses Lamore » Crosse virus and California encephalitis virus, suggesting a conserved role for Wnt signaling in bunyaviral infection. We propose a model where bunyaviruses activate Wnt-responsive genes to regulate optimal cell cycle conditions needed to promote efficient viral replication. The findings in this study should aid in the design of efficacious host-directed antiviral therapeutics. IMPORTANCE RVFV is a mosquito-borne bunyavirus that is endemic to Africa but has demonstrated a capacity for emergence in new territories (e.g., the Arabian Peninsula). As a zoonotic pathogen that primarily affects livestock, RVFV can also cause lethal hemorrhagic fever and encephalitis in humans. Currently, there are no treatments or fully licensed vaccines for this virus. Using high-throughput RNAi screening, we identified canonical Wnt signaling as an important host pathway regulating RVFV infection. The beneficial role of Wnt signaling was observed for RVFV, along with other disparate bunyaviruses, indicating a conserved bunyaviral replication mechanism involving Wnt signaling. Lastly, these studies supplement our knowledge of the fundamental mechanisms of bunyavirus infection and provide new avenues for countermeasure development against pathogenic bunyaviruses.« less

Serological and genomic evidence of Rift Valley fever virus during inter-epidemic periods in Mauritania.

PubMed

Rissmann, M; Eiden, M; El Mamy, B O; Isselmou, K; Doumbia, B; Ziegler, U; Homeier-Bachmann, T; Yahya, B; Groschup, M H

2017-04-01

Rift Valley fever virus (RVFV) is an emerging pathogen of major concern throughout Africa and the Arabian Peninsula, affecting both livestock and humans. In the past recurrent epidemics were reported in Mauritania and studies focused on the analysis of samples from affected populations during acute outbreaks. To verify characteristics and presence of RVFV during non-epidemic periods we implemented a multi-stage serological and molecular analysis. Serum samples of small ruminants, cattle and camels were obtained from Mauritania during an inter-epidemic period in 2012-2013. This paper presents a comparative analysis of potential variations and shifts of antibody presence and the capability of inter-epidemic infections in Mauritanian livestock. We observed distinct serological differences between tested species (seroprevalence: small ruminants 3·8%, cattle 15·4%, camels 32·0%). In one single bovine from Nouakchott, a recent RVF infection could be identified by the simultaneous detection of IgM antibodies and viral RNA. This study indicates the occurrence of a low-level enzootic RVFV circulation in livestock in Mauritania. Moreover, results indicate that small ruminants can preferably act as sentinels for RVF surveillance.

Genetic stability of Rift Valley fever virus MP-12 vaccine during serial passages in culture cells.

PubMed

Lokugamage, Nandadeva; Ikegami, Tetsuro

2017-01-01

Rift Valley fever (RVF) is a mosquito-borne zoonotic disease endemic to Africa which affects both ruminants and humans. RVF causes serious damage to the livestock industry and is also a threat to public health. The Rift Valley fever virus has a segmented negative-stranded RNA genome consisting of Large (L)-, Medium (M)-, and Small (S)-segments. The live-attenuated MP-12 vaccine is immunogenic in livestock and humans, and is conditionally licensed for veterinary use in the U.S. The MP-12 strain encodes 23 mutations (nine amino acid substitutions) and is attenuated through a combination of mutations in the L-, M-, and S-segments. Among them, the M-U795C, M-A3564G, and L-G3104A mutations contribute to viral attenuation through the L- and M-segments. The M-U795C, M-A3564G, L-U533C, and L-G3750A mutations are also independently responsible for temperature-sensitive (ts) phenotype. We hypothesized that a serial passage of the MP-12 vaccine in culture cells causes reversions of the MP-12 genome. The MP-12 vaccine and recombinant rMP12-ΔNSs16/198 were serially passaged 25 times. Droplet digital PCR analysis revealed that the reversion occurred at L-G3750A during passages of MP-12 in Vero or MRC-5 cells. The reversion also occurred at M-A3564G and L-U533C of rMP12-ΔNSs16/198 in Vero cells. Reversion mutations were not found in MP-12 or the variant, rMP12-TOSNSs, in the brains of mice with encephalitis. This study characterized genetic stability of the MP-12 vaccine and the potential risk of reversion mutation at the L-G3750A ts mutation after excessive viral passages in culture cells.

Persistent West Nile Virus Transmission and the Apparent Displacement St. Louis Encephalitis Virus in Southeastern California, 2003−2006

PubMed Central

REISEN, WILLIAM K.; LOTHROP, HUGH D.; WHEELER, SARAH S.; KENNSINGTON, MARC; GUTIERREZ, ARTURO; FANG, YING; GARCIA, SANDRA; LOTHROP, BRANKA

2008-01-01

West Nile virus (family Flaviviridae, genus Flavivirus, WNV) invaded the Colorado Desert biome of southern California during summer 2003 and seemed to displace previously endemic St. Louis encephalitis virus (family Flaviviridae, genus Flavivirus, SLEV, an antigenically similar Flavivirus in the Japanese encephalitis virus serocomplex). Western equine encephalomyelitis virus (family Togaviridae, genus Alphavirus, WEEV), an antigenically distinct Alphavirus, was detected during 2005 and 2006, indicating that conditions were suitable for encephalitis virus introduction and detection. Cross-protective “avian herd immunity” due to WNV infection possibly may have prevented SLEV reintroduction and/or amplification to detectable levels. During 2003−2006, WNV was consistently active at wetlands and agricultural habitats surrounding the Salton Sea where Culex tarsalis Coquillett served as the primary enzootic maintenance and amplification vector. Based on published laboratory infection studies and the current seroprevalence estimates, house sparrows, house finches, and several Ardeidae may have been important avian amplifying hosts in this region. Transmission efficiency may have been dampened by high infection rates in incompetent avian hosts, including Gamble's quail, mourning doves, common ground doves, and domestic pigeons. Early season WNV amplification and dispersal from North Shore in the southeastern portion of the Coachella Valley resulted in sporadic WNV incursions into the urbanized Upper Valley near Palm Springs, where Culex pipiens quinquefasciatus Say was the primary enzootic and bridge vector. Although relatively few human cases were detected during the 2003−2006 period, all were concentrated in the Upper Valley and were associated with high human population density and WNV infection in peridomestic populations of Cx. p. quinquefasciatus. Intensive early mosquito control during 2006 seemed to interrupt and delay transmission, perhaps setting the stage

Molecular and serological studies on the Rift Valley fever outbreak in Mauritania in 2010.

PubMed

Jäckel, S; Eiden, M; El Mamy, B O; Isselmou, K; Vina-Rodriguez, A; Doumbia, B; Groschup, M H

2013-11-01

Rift Valley fever virus (RVFV) is a vector-borne RNA virus affecting humans, livestock and wildlife. In October/November 2010, after a period of unusually heavy rainfall, a Rift Valley fever outbreak occurred in northern Mauritania causing clinical cases in cattle, sheep, goats and camels, 21 of which were of lethal outcome. The aim of this study was to obtain further information on the continuation of RVF virus activity and spread in animal species in Mauritania after this outbreak. We therefore tested sera from small ruminants, cattle and camels for the presence of viral RNA and antibodies against RVFV. These sera were collected in different parts of the country from December 2010 to February 2011 and tested with three different ELISAs and an indirect immunofluorescence assay. The results show a high seroprevalence of RVFV IgM and IgG antibodies of about 57% in all animals investigated. Moreover, in four camel sera, viral RNA was detected emphasizing the important role camels played during the latest RVF outbreak in Mauritania. The study demonstrates the continuous spread of RVFV in Mauritania after initial emergence and highlights the potential role of small ruminants and camels in virus dissemination. © 2013 Blackwell Verlag GmbH.

Protection against Rift Valley fever virus infection in mice upon administration of interferon-inducing RNA transcripts from the FMDV genome.

PubMed

Lorenzo, Gema; Rodríguez-Pulido, Miguel; López-Gil, Elena; Sobrino, Francisco; Borrego, Belén; Sáiz, Margarita; Brun, Alejandro

2014-09-01

In this work we have addressed the effect of synthetic, non-infectious, RNA transcripts, mimicking structural domains of the non-coding regions (NCRs) of the foot-and-mouth disease virus (FMDV) genome on the infection of mice with Rift Valley fever virus (RVFV). Groups of 5 mice were inoculated intraperitoneally (i.p.) with 200 μg of synthetic RNA resembling the 5'-terminal S region, the internal ribosome entry site (IRES) or the 3'-NCR of the FMDV genome. RNA inoculation was performed 24h before (-24 h), 24 h after (+24 h) or simultaneously to the challenge with a lethal dose of RVFV. Administration of the IRES RNA afforded higher survival rates than administration of S or 3'NCR transcripts either at -24h or +24h after challenge. In contrast, when RNA inoculation and viral challenge were performed simultaneously, all mice survived in both IRES- and 3'NCR-inoculated groups, with an 80% survival in mice receiving the S RNA. Among survivors, a complete correlation between significant anti-RVFV circulating antibody titers and resistance to a second lethal challenge with the virus was observed, supporting a limited viral replication in the RNA-inoculated animals upon the first challenge. All three RNA transcripts were able to induce the production of systemic antiviral and pro-inflammatory cytokines. These data show that triggering of intracellular pathogen sensing pathways constitutes a promising approach towards development of novel RVF preventive or therapeutic strategies. Copyright © 2014 Elsevier B.V. All rights reserved.

Seneca Valley Virus Suppresses Host Type I Interferon Production by Targeting Adaptor Proteins MAVS, TRIF, and TANK for Cleavage

PubMed Central

Qian, Suhong; Fan, Wenchun; Liu, Tingting; Wu, Mengge; Zhang, Huawei; Cui, Xiaofang; Zhou, Yun; Hu, Junjie; Wei, Shaozhong; Chen, Huanchun

2017-01-01

ABSTRACT Seneca Valley virus (SVV) is an oncolytic RNA virus belonging to the Picornaviridae family. Its nucleotide sequence is highly similar to those of members of the Cardiovirus genus. SVV is also a neuroendocrine cancer-selective oncolytic picornavirus that can be used for anticancer therapy. However, the interaction between SVV and its host is yet to be fully characterized. In this study, SVV inhibited antiviral type I interferon (IFN) responses by targeting different host adaptors, including mitochondrial antiviral signaling (MAVS), Toll/interleukin 1 (IL-1) receptor domain-containing adaptor inducing IFN-β (TRIF), and TRAF family member-associated NF-κB activator (TANK), via viral 3C protease (3Cpro). SVV 3Cpro mediated the cleavage of MAVS, TRIF, and TANK at specific sites, which required its protease activity. The cleaved MAVS, TRIF, and TANK lost the ability to regulate pattern recognition receptor (PRR)-mediated IFN production. The cleavage of TANK also facilitated TRAF6-induced NF-κB activation. SVV was also found to be sensitive to IFN-β. Therefore, SVV suppressed antiviral IFN production to escape host antiviral innate immune responses by cleaving host adaptor molecules. IMPORTANCE Host cells have developed various defenses against microbial pathogen infection. The production of IFN is the first line of defense against microbial infection. However, viruses have evolved many strategies to disrupt this host defense. SVV, a member of the Picornavirus genus, is an oncolytic virus that shows potential functions in anticancer therapy. It has been demonstrated that IFN can be used in anticancer therapy for certain tumors. However, the relationship between oncolytic virus and innate immune response in anticancer therapy is still not well known. In this study, we showed that SVV has evolved as an effective mechanism to inhibit host type I IFN production by using its 3Cpro to cleave the molecules MAVS, TRIF, and TANK directly. These molecules are crucial

Seneca Valley Virus Suppresses Host Type I Interferon Production by Targeting Adaptor Proteins MAVS, TRIF, and TANK for Cleavage.

PubMed

Qian, Suhong; Fan, Wenchun; Liu, Tingting; Wu, Mengge; Zhang, Huawei; Cui, Xiaofang; Zhou, Yun; Hu, Junjie; Wei, Shaozhong; Chen, Huanchun; Li, Xiangmin; Qian, Ping

2017-08-15

Seneca Valley virus (SVV) is an oncolytic RNA virus belonging to the Picornaviridae family. Its nucleotide sequence is highly similar to those of members of the Cardiovirus genus. SVV is also a neuroendocrine cancer-selective oncolytic picornavirus that can be used for anticancer therapy. However, the interaction between SVV and its host is yet to be fully characterized. In this study, SVV inhibited antiviral type I interferon (IFN) responses by targeting different host adaptors, including mitochondrial antiviral signaling (MAVS), Toll/interleukin 1 (IL-1) receptor domain-containing adaptor inducing IFN-β (TRIF), and TRAF family member-associated NF-κB activator (TANK), via viral 3C protease (3C pro ). SVV 3C pro mediated the cleavage of MAVS, TRIF, and TANK at specific sites, which required its protease activity. The cleaved MAVS, TRIF, and TANK lost the ability to regulate pattern recognition receptor (PRR)-mediated IFN production. The cleavage of TANK also facilitated TRAF6-induced NF-κB activation. SVV was also found to be sensitive to IFN-β. Therefore, SVV suppressed antiviral IFN production to escape host antiviral innate immune responses by cleaving host adaptor molecules. IMPORTANCE Host cells have developed various defenses against microbial pathogen infection. The production of IFN is the first line of defense against microbial infection. However, viruses have evolved many strategies to disrupt this host defense. SVV, a member of the Picornavirus genus, is an oncolytic virus that shows potential functions in anticancer therapy. It has been demonstrated that IFN can be used in anticancer therapy for certain tumors. However, the relationship between oncolytic virus and innate immune response in anticancer therapy is still not well known. In this study, we showed that SVV has evolved as an effective mechanism to inhibit host type I IFN production by using its 3C pro to cleave the molecules MAVS, TRIF, and TANK directly. These molecules are crucial for

Virulence factor NSs of rift valley fever virus recruits the F-box protein FBXO3 to degrade subunit p62 of general transcription factor TFIIH.

PubMed

Kainulainen, Markus; Habjan, Matthias; Hubel, Philipp; Busch, Laura; Lau, Simone; Colinge, Jacques; Superti-Furga, Giulio; Pichlmair, Andreas; Weber, Friedemann

2014-03-01

The nonstructural protein NSs is the main virulence factor of Rift Valley fever virus (RVFV; family Bunyaviridae, genus Phlebovirus), a serious pathogen of livestock and humans in Africa. RVFV NSs blocks transcriptional upregulation of antiviral type I interferons (IFN) and destroys the general transcription factor TFIIH subunit p62 via the ubiquitin/proteasome pathway. Here, we identified a subunit of E3 ubiquitin ligases, F-box protein FBXO3, as a host cell interactor of NSs. Small interfering RNA (siRNA)-mediated depletion of FBXO3 rescued p62 protein levels in RVFV-infected cells and elevated IFN transcription by 1 order of magnitude. NSs interacts with the full-length FBXO3 protein as well as with a truncated isoform that lacks the C-terminal acidic and poly(R)-rich domains. These isoforms are present in both the nucleus and the cytoplasm. NSs exclusively removes the nuclear pool of full-length FBXO3, likely due to consumption during the degradation process. F-box proteins form the variable substrate recognition subunit of the so-called SCF ubiquitin ligases, which also contain the constant components Skp1, cullin 1 (or cullin 7), and Rbx1. siRNA knockdown of Skp1 also protected p62 from degradation, suggesting involvement in NSs action. However, knockdown of cullin 1, cullin 7, or Rbx1 could not rescue p62 degradation by NSs. Our data show that the enzymatic removal of p62 via the host cell factor FBXO3 is a major mechanism of IFN suppression by RVFV. Rift Valley fever virus is a serious emerging pathogen of animals and humans. Its main virulence factor, NSs, enables unhindered virus replication by suppressing the antiviral innate immune system. We identified the E3 ubiquitin ligase FBXO3 as a novel host cell interactor of NSs. NSs recruits FBXO3 to destroy the general host cell transcription factor TFIIH-p62, resulting in suppression of the transcriptional upregulation of innate immunity.

Virulence Factor NSs of Rift Valley Fever Virus Recruits the F-Box Protein FBXO3 To Degrade Subunit p62 of General Transcription Factor TFIIH

PubMed Central

Kainulainen, Markus; Habjan, Matthias; Hubel, Philipp; Busch, Laura; Lau, Simone; Colinge, Jacques; Superti-Furga, Giulio; Pichlmair, Andreas

2014-01-01

ABSTRACT The nonstructural protein NSs is the main virulence factor of Rift Valley fever virus (RVFV; family Bunyaviridae, genus Phlebovirus), a serious pathogen of livestock and humans in Africa. RVFV NSs blocks transcriptional upregulation of antiviral type I interferons (IFN) and destroys the general transcription factor TFIIH subunit p62 via the ubiquitin/proteasome pathway. Here, we identified a subunit of E3 ubiquitin ligases, F-box protein FBXO3, as a host cell interactor of NSs. Small interfering RNA (siRNA)-mediated depletion of FBXO3 rescued p62 protein levels in RVFV-infected cells and elevated IFN transcription by 1 order of magnitude. NSs interacts with the full-length FBXO3 protein as well as with a truncated isoform that lacks the C-terminal acidic and poly(R)-rich domains. These isoforms are present in both the nucleus and the cytoplasm. NSs exclusively removes the nuclear pool of full-length FBXO3, likely due to consumption during the degradation process. F-box proteins form the variable substrate recognition subunit of the so-called SCF ubiquitin ligases, which also contain the constant components Skp1, cullin 1 (or cullin 7), and Rbx1. siRNA knockdown of Skp1 also protected p62 from degradation, suggesting involvement in NSs action. However, knockdown of cullin 1, cullin 7, or Rbx1 could not rescue p62 degradation by NSs. Our data show that the enzymatic removal of p62 via the host cell factor FBXO3 is a major mechanism of IFN suppression by RVFV. IMPORTANCE Rift Valley fever virus is a serious emerging pathogen of animals and humans. Its main virulence factor, NSs, enables unhindered virus replication by suppressing the antiviral innate immune system. We identified the E3 ubiquitin ligase FBXO3 as a novel host cell interactor of NSs. NSs recruits FBXO3 to destroy the general host cell transcription factor TFIIH-p62, resulting in suppression of the transcriptional upregulation of innate immunity. PMID:24403578

Postepidemic analysis of Rift Valley fever virus transmission in northeastern kenya: a village cohort study.

PubMed

LaBeaud, A Desirée; Muiruri, Samuel; Sutherland, Laura J; Dahir, Saidi; Gildengorin, Ginny; Morrill, John; Muchiri, Eric M; Peters, Clarence J; King, Charles H

2011-08-01

In endemic areas, Rift Valley fever virus (RVFV) is a significant threat to both human and animal health. Goals of this study were to measure human anti-RVFV seroprevalence in a high-risk area following the 2006-2007 Kenyan Rift Valley Fever (RVF) epidemic, to identify risk factors for interval seroconversion, and to monitor individuals previously exposed to RVFV in order to document the persistence of their anti-RVFV antibodies. We conducted a village cohort study in Ijara District, Northeastern Province, Kenya. One hundred two individuals tested for RVFV exposure before the 2006-2007 RVF outbreak were restudied to determine interval anti-RVFV seroconversion and persistence of humoral immunity since 2006. Ninety-two additional subjects were enrolled from randomly selected households to help identify risk factors for current seropositivity. Overall, 44/194 or 23% (CI(95%):17%-29%) of local residents were RVFV seropositive. 1/85 at-risk individuals restudied in the follow-up cohort had seroconverted since early 2006. 27/92 (29%, CI(95%): 20%-39%) of newly tested individuals were seropositive. All 13 individuals with positive titers (by plaque reduction neutralization testing (PRNT₈₀) in 2006 remained positive in 2009. After adjustment in multivariable logistic models, age, village, and drinking raw milk were significantly associated with RVFV seropositivity. Visual impairment (defined as ≤ 20/80) was much more likely in the RVFV-seropositive group (P<0.0001). Our results highlight significant variability in RVFV exposure in two neighboring villages having very similar climate, terrain, and insect density. Among those with previous exposure, RVFV titers remained at > 1∶40 for more than 3 years. In concordance with previous studies, residents of the more rural village were more likely to be seropositive and RVFV seropositivity was associated with poor visual acuity. Raw milk consumption was strongly associated with RVFV exposure, which may represent an

Postepidemic Analysis of Rift Valley Fever Virus Transmission in Northeastern Kenya: A Village Cohort Study

PubMed Central

LaBeaud, A. Desirée; Muiruri, Samuel; Sutherland, Laura J.; Dahir, Saidi; Gildengorin, Ginny; Morrill, John; Muchiri, Eric M.; Peters, Clarence J.; King, Charles H.

2011-01-01

Background In endemic areas, Rift Valley fever virus (RVFV) is a significant threat to both human and animal health. Goals of this study were to measure human anti-RVFV seroprevalence in a high-risk area following the 2006–2007 Kenyan Rift Valley Fever (RVF) epidemic, to identify risk factors for interval seroconversion, and to monitor individuals previously exposed to RVFV in order to document the persistence of their anti-RVFV antibodies. Methodology/Findings We conducted a village cohort study in Ijara District, Northeastern Province, Kenya. One hundred two individuals tested for RVFV exposure before the 2006–2007 RVF outbreak were restudied to determine interval anti-RVFV seroconversion and persistence of humoral immunity since 2006. Ninety-two additional subjects were enrolled from randomly selected households to help identify risk factors for current seropositivity. Overall, 44/194 or 23% (CI95%:17%–29%) of local residents were RVFV seropositive. 1/85 at-risk individuals restudied in the follow-up cohort had seroconverted since early 2006. 27/92 (29%, CI95%: 20%–39%) of newly tested individuals were seropositive. All 13 individuals with positive titers (by plaque reduction neutralization testing (PRNT80)) in 2006 remained positive in 2009. After adjustment in multivariable logistic models, age, village, and drinking raw milk were significantly associated with RVFV seropositivity. Visual impairment (defined as ≤20/80) was much more likely in the RVFV-seropositive group (P<0.0001). Conclusions Our results highlight significant variability in RVFV exposure in two neighboring villages having very similar climate, terrain, and insect density. Among those with previous exposure, RVFV titers remained at >1∶40 for more than 3 years. In concordance with previous studies, residents of the more rural village were more likely to be seropositive and RVFV seropositivity was associated with poor visual acuity. Raw milk consumption was strongly associated with

Laboratory Validation of the Sand Fly Fever Virus Antigen Assay

DTIC Science & Technology

2015-12-01

several commercially available assays from VecTOR Test Systems Inc. for malaria, West Nile virus, Rift Valley fever virus, dengue , chikungunya, and...Sabin AB. 1955. Recent advances in our knowledge of dengue and sandfly fever. Am J Trop Med Hyg 4:198–207. Sather GE. 1970. Catalogue of arthropod

A ΩXaV motif in the Rift Valley fever virus NSs protein is essential for degrading p62, forming nuclear filaments and virulence

PubMed Central

Cyr, Normand; de la Fuente, Cynthia; Lecoq, Lauriane; Guendel, Irene; Chabot, Philippe R.; Kehn-Hall, Kylene; Omichinski, James G.

2015-01-01

Rift Valley fever virus (RVFV) is a single-stranded RNA virus capable of inducing fatal hemorrhagic fever in humans. A key component of RVFV virulence is its ability to form nuclear filaments through interactions between the viral nonstructural protein NSs and the host general transcription factor TFIIH. Here, we identify an interaction between a ΩXaV motif in NSs and the p62 subunit of TFIIH. This motif in NSs is similar to ΩXaV motifs found in nucleotide excision repair (NER) factors and transcription factors known to interact with p62. Structural and biophysical studies demonstrate that NSs binds to p62 in a similar manner as these other factors. Functional studies in RVFV-infected cells show that the ΩXaV motif is required for both nuclear filament formation and degradation of p62. Consistent with the fact that the RVFV can be distinguished from other Bunyaviridae-family viruses due to its ability to form nuclear filaments in infected cells, the motif is absent in the NSs proteins of other Bunyaviridae-family viruses. Taken together, our studies demonstrate that p62 binding to NSs through the ΩXaV motif is essential for degrading p62, forming nuclear filaments and enhancing RVFV virulence. In addition, these results show how the RVFV incorporates a simple motif into the NSs protein that enables it to functionally mimic host cell proteins that bind the p62 subunit of TFIIH. PMID:25918396

A ΩXaV motif in the Rift Valley fever virus NSs protein is essential for degrading p62, forming nuclear filaments and virulence.

PubMed

Cyr, Normand; de la Fuente, Cynthia; Lecoq, Lauriane; Guendel, Irene; Chabot, Philippe R; Kehn-Hall, Kylene; Omichinski, James G

2015-05-12

Rift Valley fever virus (RVFV) is a single-stranded RNA virus capable of inducing fatal hemorrhagic fever in humans. A key component of RVFV virulence is its ability to form nuclear filaments through interactions between the viral nonstructural protein NSs and the host general transcription factor TFIIH. Here, we identify an interaction between a ΩXaV motif in NSs and the p62 subunit of TFIIH. This motif in NSs is similar to ΩXaV motifs found in nucleotide excision repair (NER) factors and transcription factors known to interact with p62. Structural and biophysical studies demonstrate that NSs binds to p62 in a similar manner as these other factors. Functional studies in RVFV-infected cells show that the ΩXaV motif is required for both nuclear filament formation and degradation of p62. Consistent with the fact that the RVFV can be distinguished from other Bunyaviridae-family viruses due to its ability to form nuclear filaments in infected cells, the motif is absent in the NSs proteins of other Bunyaviridae-family viruses. Taken together, our studies demonstrate that p62 binding to NSs through the ΩXaV motif is essential for degrading p62, forming nuclear filaments and enhancing RVFV virulence. In addition, these results show how the RVFV incorporates a simple motif into the NSs protein that enables it to functionally mimic host cell proteins that bind the p62 subunit of TFIIH.

The Nonstructural Protein NSs Induces a Variable Antibody Response in Domestic Ruminants Naturally Infected with Rift Valley Fever Virus

PubMed Central

Fernandez, José-Carlos; Billecocq, Agnès; Durand, Jean Paul; Cêtre-Sossah, Catherine; Cardinale, Eric; Marianneau, Philippe; Pépin, Michel; Tordo, Noël

2012-01-01

Rift Valley fever (RVF) is an emerging zoonosis in Africa which has spread to Egypt, the Arabian Peninsula, Madagascar, and Comoros. RVF virus (RVFV) (Bunyaviridae family, Phlebovirus genus) causes a wide range of symptoms in humans, from benign fever to fatal hemorrhagic fever. Ruminants are severely affected by the disease, which leads to a high rate of mortality in young animals and to abortions and teratogenesis in pregnant females. Diagnostic tests include virus isolation and genome or antibody detection. During RVFV infection, the nucleoprotein encapsidating the tripartite RNA genome is expressed in large amounts and raises a robust antibody response, while the envelope glycoproteins elicit neutralizing antibodies which play a major role in protection. Much less is known about the antigenicity/immunogenicity of the nonstructural protein NSs, which is a major virulence factor. Here we have developed a competitive enzyme-linked immunosorbent assay (ELISA) enabling detection of low levels of NSs-specific antibodies in naturally infected or vaccinated ruminants. Detection of the NSs antibodies was validated by Western blotting. Altogether, our data showed that the NSs antibodies were detected in only 55% of animals naturally infected by RVFV, indicating that NSs does not induce a consistently high immune response. These results are discussed in light of differentiation between infected and vaccinated animals (DIVA) tests distinguishing naturally infected animals and those vaccinated with NSs-defective vaccines. PMID:22072723

The nonstructural protein NSs induces a variable antibody response in domestic ruminants naturally infected with Rift Valley fever virus.

PubMed

Fernandez, José-Carlos; Billecocq, Agnès; Durand, Jean Paul; Cêtre-Sossah, Catherine; Cardinale, Eric; Marianneau, Philippe; Pépin, Michel; Tordo, Noël; Bouloy, Michèle

2012-01-01

Rift Valley fever (RVF) is an emerging zoonosis in Africa which has spread to Egypt, the Arabian Peninsula, Madagascar, and Comoros. RVF virus (RVFV) (Bunyaviridae family, Phlebovirus genus) causes a wide range of symptoms in humans, from benign fever to fatal hemorrhagic fever. Ruminants are severely affected by the disease, which leads to a high rate of mortality in young animals and to abortions and teratogenesis in pregnant females. Diagnostic tests include virus isolation and genome or antibody detection. During RVFV infection, the nucleoprotein encapsidating the tripartite RNA genome is expressed in large amounts and raises a robust antibody response, while the envelope glycoproteins elicit neutralizing antibodies which play a major role in protection. Much less is known about the antigenicity/immunogenicity of the nonstructural protein NSs, which is a major virulence factor. Here we have developed a competitive enzyme-linked immunosorbent assay (ELISA) enabling detection of low levels of NSs-specific antibodies in naturally infected or vaccinated ruminants. Detection of the NSs antibodies was validated by Western blotting. Altogether, our data showed that the NSs antibodies were detected in only 55% of animals naturally infected by RVFV, indicating that NSs does not induce a consistently high immune response. These results are discussed in light of differentiation between infected and vaccinated animals (DIVA) tests distinguishing naturally infected animals and those vaccinated with NSs-defective vaccines.

Rift Valley Fever Virus Structural and Nonstructural Proteins: Recombinant Protein Expression and Immunoreactivity Against Antisera from Sheep

PubMed Central

Faburay, Bonto; Wilson, William; McVey, D. Scott; Drolet, Barbara S.; Weingartl, Hana; Madden, Daniel; Young, Alan; Ma, Wenjun

2013-01-01

Abstract The Rift Valley fever virus (RVFV) encodes the structural proteins nucleoprotein (N), aminoterminal glycoprotein (Gn), carboxyterminal glycoprotein (Gc), and L protein, 78-kD, and the nonstructural proteins NSm and NSs. Using the baculovirus system, we expressed the full-length coding sequence of N, NSs, NSm, Gc, and the ectodomain of the coding sequence of the Gn glycoprotein derived from the virulent strain of RVFV ZH548. Western blot analysis using anti-His antibodies and monoclonal antibodies against Gn and N confirmed expression of the recombinant proteins, and in vitro biochemical analysis showed that the two glycoproteins, Gn and Gc, were expressed in glycosylated form. Immunoreactivity profiles of the recombinant proteins in western blot and in indirect enzyme-linked immunosorbent assay against a panel of antisera obtained from vaccinated or wild type (RVFV)-challenged sheep confirmed the results obtained with anti-His antibodies and demonstrated the suitability of the baculo-expressed antigens for diagnostic assays. In addition, these recombinant proteins could be valuable for the development of diagnostic methods that differentiate infected from vaccinated animals (DIVA). PMID:23962238

[Viruses and civilization].

PubMed

Chastel, C

1999-01-01

A few million years ago, when primates moved from the east African forest to the savannah, they were already infected with endogenous viruses and occultly transmitted them to the prime Homo species. However it was much later with the building of the first large cities in Mesopotamia that interhuman viral transmission began in earnest. Spreading was further enhanced with the organization of the Egyptian, Greek, Roman, and Arab empires around the Mediterranean. Discovery of the New World in 1492 led to an unprecedented clash of civilizations and the destruction of pre-Columbian Indian civilizations. It also led to a rapid spread of viruses across the Atlantic Ocean with the emergence of yellow fever and appearance of smallpox and measles throughout the world. However the greatest opportunities for worldwide viral development have been created by our present, modern civilization. This fact is illustrated by epidemic outbreaks of human immunodeficiency virus, Venezuela hemorrhagic fever, Rift valley fever virus, and monkey pox virus. Close analysis underscores the major role of human intervention in producing these events.

Evaluation of positive Rift Valley fever virus formalin-fixed paraffin embedded samples as a source of sequence data for retrospective phylogenetic analysis.

PubMed

Mubemba, B; Thompson, P N; Odendaal, L; Coetzee, P; Venter, E H

2017-05-01

Rift Valley fever (RVF), caused by an arthropod borne Phlebovirus in the family Bunyaviridae, is a haemorrhagic disease that affects ruminants and humans. Due to the zoonotic nature of the virus, a biosafety level 3 laboratory is required for isolation of the virus. Fresh and frozen samples are the preferred sample type for isolation and acquisition of sequence data. However, these samples are scarce in addition to posing a health risk to laboratory personnel. Archived formalin-fixed, paraffin-embedded (FFPE) tissue samples are safe and readily available, however FFPE derived RNA is in most cases degraded and cross-linked in peptide bonds and it is unknown whether the sample type would be suitable as reference material for retrospective phylogenetic studies. A RT-PCR assay targeting a 490 nt portion of the structural G N glycoprotein encoding gene of the RVFV M-segment was applied to total RNA extracted from archived RVFV positive FFPE samples. Several attempts to obtain target amplicons were unsuccessful. FFPE samples were then analysed using next generation sequencing (NGS), i.e. Truseq ® (Illumina) and sequenced on the Miseq ® genome analyser (Illumina). Using reference mapping, gapped virus sequence data of varying degrees of shallow depth was aligned to a reference sequence. However, the NGS did not yield long enough contigs that consistently covered the same genome regions in all samples to allow phylogenetic analysis. Copyright © 2017 Elsevier B.V. All rights reserved.

N-Glycans on the Rift Valley Fever Virus Envelope Glycoproteins Gn and Gc Redundantly Support Viral Infection via DC-SIGN.

PubMed

Phoenix, Inaia; Nishiyama, Shoko; Lokugamage, Nandadeva; Hill, Terence E; Huante, Matthew B; Slack, Olga A L; Carpio, Victor H; Freiberg, Alexander N; Ikegami, Tetsuro

2016-05-23

Rift Valley fever is a mosquito-transmitted, zoonotic disease that infects humans and ruminants. Dendritic cell specific intercellular adhesion molecule 3 (ICAM-3) grabbing non-integrin (DC-SIGN) acts as a receptor for members of the phlebovirus genus. The Rift Valley fever virus (RVFV) glycoproteins (Gn/Gc) encode five putative N-glycan sequons (asparagine (N)-any amino acid (X)-serine (S)/threonine (T)) at positions: N438 (Gn), and N794, N829, N1035, and N1077 (Gc). The N-glycosylation profile and significance in viral infection via DC-SIGN have not been elucidated. Gc N-glycosylation was first evaluated by using Gc asparagine (N) to glutamine (Q) mutants. Subsequently, we generated a series of recombinant RVFV MP-12 strain mutants, which encode N-to-Q mutations, and the infectivity of each mutant in Jurkat cells stably expressing DC-SIGN was evaluated. Results showed that Gc N794, N1035, and N1077 were N-glycosylated but N829 was not. Gc N1077 was heterogeneously N-glycosylated. RVFV Gc made two distinct N-glycoforms: "Gc-large" and "Gc-small", and N1077 was responsible for "Gc-large" band. RVFV showed increased infection of cells expressing DC-SIGN compared to cells lacking DC-SIGN. Infection via DC-SIGN was increased in the presence of either Gn N438 or Gc N1077. Our study showed that N-glycans on the Gc and Gn surface glycoproteins redundantly support RVFV infection via DC-SIGN.

Nuclear relocalization of polyadenylate binding protein during rift valley fever virus infection involves expression of the NSs gene.

PubMed

Copeland, Anna Maria; Altamura, Louis A; Van Deusen, Nicole M; Schmaljohn, Connie S

2013-11-01

Rift Valley fever virus (RVFV), an ambisense member of the family Bunyaviridae, genus Phlebovirus, is the causative agent of Rift Valley fever, an important zoonotic infection in Africa and the Middle East. Phlebovirus proteins are translated from virally transcribed mRNAs that, like host mRNA, are capped but, unlike host mRNAs, are not polyadenylated. Here, we investigated the role of PABP1 during RVFV infection of HeLa cells. Immunofluorescence studies of infected cells demonstrated a gross relocalization of PABP1 to the nucleus late in infection. Immunofluorescence microscopy studies of nuclear proteins revealed costaining between PABP1 and markers of nuclear speckles. PABP1 relocalization was sharply decreased in cells infected with a strain of RVFV lacking the gene encoding the RVFV nonstructural protein S (NSs). To determine whether PABP1 was required for RVFV infection, we measured the production of nucleocapsid protein (N) in cells transfected with small interfering RNAs (siRNAs) targeting PABP1. We found that the overall percentage of RVFV N-positive cells was not changed by siRNA treatment, indicating that PABP1 was not required for RVFV infection. However, when we analyzed populations of cells producing high versus low levels of PABP1, we found that the percentage of RVFV N-positive cells was decreased in cell populations producing physiologic levels of PABP1 and increased in cells with reduced levels of PABP1. Together, these results suggest that production of the NSs protein during RVFV infection leads to sequestration of PABP1 in the nuclear speckles, creating a state within the cell that favors viral protein production.

NSs Virulence Factor of Rift Valley Fever Virus Engages the F-Box Proteins FBXW11 and β-TRCP1 To Degrade the Antiviral Protein Kinase PKR.

PubMed

Kainulainen, Markus; Lau, Simone; Samuel, Charles E; Hornung, Veit; Weber, Friedemann

2016-07-01

Rift Valley fever virus (RVFV, family Bunyaviridae, genus Phlebovirus) is a relevant pathogen of both humans and livestock in Africa. The nonstructural protein NSs is a major virulence factor known to suppress the type I interferon (IFN) response by inhibiting host cell transcription and by proteasomal degradation of a major antiviral IFN effector, the translation-inhibiting protein kinase PKR. Here, we identified components of the modular SCF (Skp1, Cul1, F-box protein)-type E3 ubiquitin ligases as mediators of PKR destruction by NSs. Small interfering RNAs (siRNAs) against the conserved SCF subunit Skp1 protected PKR from NSs-mediated degradation. Consequently, RVFV replication was severely reduced in Skp1-depleted cells when PKR was present. SCF complexes have a variable F-box protein subunit that determines substrate specificity for ubiquitination. We performed an siRNA screen for all (about 70) human F-box proteins and found FBXW11 to be involved in PKR degradation. The partial stabilization of PKR by FBXW11 depletion upregulated PKR autophosphorylation and phosphorylation of the PKR substrate eIF2α and caused a shutoff of host cell protein synthesis in RVFV-infected cells. To maximally protect PKR from the action of NSs, knockdown of structurally and functionally related FBXW1 (also known as β-TRCP1), in addition to FBXW11 deletion, was necessary. Consequently, NSs was found to interact with both FBXW11 and β-TRCP1. Thus, NSs eliminates the antiviral kinase PKR by recruitment of SCF-type E3 ubiquitin ligases containing FBXW11 and β-TRCP1 as substrate recognition subunits. This antagonism of PKR by NSs is essential for efficient RVFV replication in mammalian cells. Rift Valley fever virus is a pathogen of humans and animals that has the potential to spread from Africa and the Arabian Peninsula to other regions. A major virulence mechanism is the proteasomal degradation of the antiviral kinase PKR by the viral protein NSs. Here, we demonstrate that NSs

NSs Virulence Factor of Rift Valley Fever Virus Engages the F-Box Proteins FBXW11 and β-TRCP1 To Degrade the Antiviral Protein Kinase PKR

PubMed Central

Kainulainen, Markus; Lau, Simone; Samuel, Charles E.; Hornung, Veit

2016-01-01

ABSTRACT Rift Valley fever virus (RVFV, family Bunyaviridae, genus Phlebovirus) is a relevant pathogen of both humans and livestock in Africa. The nonstructural protein NSs is a major virulence factor known to suppress the type I interferon (IFN) response by inhibiting host cell transcription and by proteasomal degradation of a major antiviral IFN effector, the translation-inhibiting protein kinase PKR. Here, we identified components of the modular SCF (Skp1, Cul1, F-box protein)-type E3 ubiquitin ligases as mediators of PKR destruction by NSs. Small interfering RNAs (siRNAs) against the conserved SCF subunit Skp1 protected PKR from NSs-mediated degradation. Consequently, RVFV replication was severely reduced in Skp1-depleted cells when PKR was present. SCF complexes have a variable F-box protein subunit that determines substrate specificity for ubiquitination. We performed an siRNA screen for all (about 70) human F-box proteins and found FBXW11 to be involved in PKR degradation. The partial stabilization of PKR by FBXW11 depletion upregulated PKR autophosphorylation and phosphorylation of the PKR substrate eIF2α and caused a shutoff of host cell protein synthesis in RVFV-infected cells. To maximally protect PKR from the action of NSs, knockdown of structurally and functionally related FBXW1 (also known as β-TRCP1), in addition to FBXW11 deletion, was necessary. Consequently, NSs was found to interact with both FBXW11 and β-TRCP1. Thus, NSs eliminates the antiviral kinase PKR by recruitment of SCF-type E3 ubiquitin ligases containing FBXW11 and β-TRCP1 as substrate recognition subunits. This antagonism of PKR by NSs is essential for efficient RVFV replication in mammalian cells. IMPORTANCE Rift Valley fever virus is a pathogen of humans and animals that has the potential to spread from Africa and the Arabian Peninsula to other regions. A major virulence mechanism is the proteasomal degradation of the antiviral kinase PKR by the viral protein NSs. Here, we

Two distinct phylogenetic clades of infectious hematopoietic necrosis virus overlap within the Columbia River basin

USGS Publications Warehouse

Garver, K.A.; Troyer, R.M.; Kurath, G.

2003-01-01

Infectious hematopoietic necrosis virus (IHNV), an aquatic rhabdovirus, causes a highly lethal disease of salmonid fish in North America. To evaluate the genetic diversity of IHNV from throughout the Columbia River basin, excluding the Hagerman Valley, Idaho, the sequences of a 303 nt region of the glycoprotein gene (mid-G) of 120 virus isolates were determined. Sequence comparisons revealed 30 different sequence types, with a maximum nucleotide diversity of 7.3% (22 mismatches) and an intrapopulational nucleotide diversity of 0.018. This indicates that the genetic diversity of IHNV within the Columbia River basin is 3-fold higher than in Alaska, but 2-fold lower than in the Hagerman Valley, Idaho. Phylogenetic analyses separated the Columbia River basin IHNV isolates into 2 major clades, designated U and M. The 2 clades geographically overlapped within the lower Columbia River basin and in the lower Snake River and tributaries, while the upper Columbia River basin had only U clade and the upper Snake River basin had only M clade virus types. These results suggest that there are co-circulating lineages of IHNV present within specific areas of the Columbia River basin. The epidemiological significance of these findings provided insight into viral traffic patterns exhibited by IHNV in the Columbia River basin, with specific relevance to how the Columbia River basin IHNV types were related to those in the Hagerman Valley. These analyses indicate that there have likely been 2 historical events in which Hagerman Valley IHNV types were introduced and became established in the lower Columbia River basin. However, the data also clearly indicates that the Hagerman Valley is not a continuous source of waterborne virus infecting salmonid stocks downstream.

Single-Dose Intranasal Treatment with DEF201 (Adenovirus Vectored Consensus Interferon) Prevents Lethal Disease Due to Rift Valley Fever Virus Challenge

PubMed Central

Gowen, Brian B.; Ennis, Jane; Bailey, Kevin W.; Vest, Zachary; Scharton, Dionna; Sefing, Eric J.; Turner, Jeffrey D.

2014-01-01

Rift Valley fever virus (RVFV) causes severe disease in humans and ungulates. The virus can be transmitted by mosquitoes, direct contact with infected tissues or fluids, or aerosol, making it a significant biological threat for which there is no approved vaccine or therapeutic. Herein we describe the evaluation of DEF201, an adenovirus-vectored interferon alpha which addresses the limitations of recombinant interferon alpha protein (cost, short half-life), as a pre- and post-exposure treatment in a lethal hamster RVFV challenge model. DEF201 was delivered intranasally to stimulate mucosal immunity and effectively bypass any pre-existing immunity to the vector. Complete protection against RVFV infection was observed from a single dose of DEF201 administered one or seven days prior to challenge while all control animals succumbed within three days of infection. Efficacy of treatment administered two weeks prior to challenge was limited. Post‑exposure, DEF201 was able to confer significant protection when dosed at 30 min or 6 h, but not at 24 h post-RVFV challenge. Protection was associated with reductions in serum and tissue viral loads. Our findings suggest that DEF201 may be a useful countermeasure against RVFV infection and further demonstrates its broad-spectrum capacity to stimulate single dose protective immunity. PMID:24662673

Studies of Infection and dissemination of Rift Valley Fever Virus in Mosquitoes

DTIC Science & Technology

1989-04-19

foregut- midgut junction; and (5) preliminary studies with regard to the mosquito cell surface receptor molecule for RVF virus. Major results and...conclusions include: (1) The patterns of midgut infection, escape of virus from the midgut , and distribution of virus after entering the hemocoel in Aedes...epithelium via cells at the foregut- midgut junction. (5) We have found evidence of specific binding of components of formalin-killed RVF virus (vaccine

A Tomato necrotic dwarf virus isolate from Datura with poor transmissibility by the whitefly, Bemisia tabaci

USDA-ARS?s Scientific Manuscript database

Tomato necrotic dwarf virus (ToNDV); genus Torradovirus, is a whitefly-transmitted virus that caused significant losses for tomato production in the Imperial Valley of California during the 1980s. The virus causes severe stunting, dwarfing of leaves, foliar and fruit necrosis, and greatly reduced f...

Mosquitoes and the environment in Nile Delta villages with previous rift valley fever activity

USDA-ARS?s Scientific Manuscript database

Egypt is affected by serious human and animal mosquito-borne diseases such as Rift Valley fever (RVF). We investigated how potential RVF virus mosquito vector populations are affected by environmental conditions in the Nile Delta region of Egypt by collecting mosquitoes and environmental data from t...

Rift Valley fever virus infection in African Buffalo (Syncerus caffer) herds in rural South Africa: Evidence of interepidemic transmission

USGS Publications Warehouse

LaBeaud, A.D.; Cross, P.C.; Getz, W.M.; Glinka, A.; King, C.H.

2011-01-01

Rift Valley fever virus (RVFV) is an emerging biodefense pathogen that poses significant threats to human and livestock health. To date, the interepidemic reservoirs of RVFV are not well defined. In a longitudinal survey of infectious diseases among African buffalo during 2000-2006, 550 buffalo were tested for antibodies against RVFV in 820 capture events in 302 georeferenced locations in Kruger National Park, South Africa. Overall, 115 buffalo (21%) were seropositive. Seroprevalence of RVFV was highest (32%) in the first study year, and decreased progressively in subsequent years, but had no detectable impact on survival. Nine (7%) of 126 resampled, initially seronegative animals seroconverted during periods outside any reported regional RVFV outbreaks. Seroconversions for RVFV were detected in significant temporal clusters during 2001-2003 and in 2004. These findings highlight the potential importance of wildlife as reservoirs for RVFV and interepidemic RVFV transmission in perpetuating regional RVFV transmission risk. Copyright ?? 2011 by The American Society of Tropical Medicine and Hygiene.

Pathogenic effects of Rift Valley fever virus NSs gene are alleviated in cultured cells by expressed antiviral short hairpin RNAs.

PubMed

Scott, Tristan; Paweska, Janusz T; Arbuthnot, Patrick; Weinberg, Marc S

2012-01-01

Rift Valley fever virus (RVFV), a member of the Bunyaviridae family, may cause severe hepatitis, encephalitis and haemorrhagic fever in humans. There are currently no available licensed vaccines or therapies to treat the viral infection in humans. RNA interference (RNAi)-based viral gene silencing offers a promising approach to inhibiting replication of this highly pathogenic virus. The small (S) segment of the RVFV tripartite genome carries the genetic determinates for pathogenicity during infection. This segment encodes the non-structural S (NSs) and essential nucleocapsid (N) genes. To advance RNAi-based inhibition of RVFV replication, we designed several Pol III short hairpin RNA (shRNA) expression cassettes against the NSs and N genes, including a multimerized plasmid vector that included four shRNA expression cassettes. Effective target silencing was demonstrated using full- and partial-length target reporter assays, and confirmed by western blot analysis of exogenous N and NSs expression. Small RNA northern blots showed detectable RNAi guide strand formation from single and multimerized shRNA constructs. Using a cell culture model of RVFV replication, shRNAs targeting the N gene decreased intracellular nucleocapsid protein concentration and viral replication. The shRNAs directed against the NSs gene reduced NSs protein concentrations and alleviated NSs-mediated cytotoxicity, which may be caused by host transcription suppression. These data are the first demonstration that RNAi activators have a potential therapeutic benefit for countering RVFV infection.

Serological evidence of Rift Valley fever virus circulation in sheep and goats in Zambézia Province, Mozambique.

PubMed

Fafetine, José; Neves, Luis; Thompson, Peter N; Paweska, Janusz T; Rutten, Victor P M G; Coetzer, J A W

2013-01-01

Rift Valley fever (RVF) is endemic in most parts of Africa and has also been reported to occur in the Arabian Peninsula. It is responsible for significant morbidity and mortality, particularly in livestock, but also in humans. During the last two decades several outbreaks of RVF have been reported in countries in Southern Africa. In contrast to other countries, no clinical disease has been reported in Mozambique during this period. In a serological study conducted in 2007 in five districts of Zambézia Province, Mozambique, of a total of 654 small ruminants sampled (277 sheep and 377 goats), 35.8% of sheep sera and 21.2% of goat sera were positive for RVF virus (RVFV) antibodies in a virus neutralization test (VN) and in an IgG enzyme-linked immunosorbent assay (ELISA). In 2010, a cross-sectional survey was conducted in 313 sheep and 449 goats in two districts of the same province. This study revealed an overall seropositivity rate of 9.2% in sheep and 11.6% in goat and an increased likelihood of being seropositive in older animals (OR = 7.3; p<0.001) using an IgG ELISA. 29 out of 240 animals assessed for RVF specific IgM by ELISA were positive, suggesting recent exposure to RVFV. However, a longitudinal study carried out between September 2010 and April 2011 in a cohort of 125 of these animals (74 sheep and 51 goats) failed to demonstrate seroconversion. The results of the study indicate that RVFV circulates sub-clinically in domestic small ruminants in Zambézia Province.

Rift Valley fever on the east coast of Madagascar.

PubMed

Morvan, J; Saluzzo, J F; Fontenille, D; Rollin, P E; Coulanges, P

1991-01-01

In March 1990, a Rift Valley fever virus (RVFV) outbreak was suspected in the district of Fenerive on the east coast of Madagascar after an abnormally high incidence of abortions and disease in livestock. Sera from humans and cattle were tested for RVFV antibodies by immunofluorescence assay (IFA) and ELISA-IgM capture. Sera and mosquitoes collected in the same area were tested for virus isolation by tissue culture and suckling mouse intracerebral inoculation, and for antigen detection by an ELISA antigen capture assay. Among cattle from the area, RVFV antibody prevalence was 58.6% by IFA and 29.6% by ELISA-IgM. In contrast, human populations in the same area had a lower RVFV antibody prevalence, with 8.01% IFA and 5.4% IgM-positive sera. No RVFV antigen was detected and virus isolation was unsuccessful from the sera and mosquito pools tested. Different hypotheses concerning the emergence and diffusion of RVFV in this area and the occurrence of the outbreak are discussed.

Nonstructural NSs protein of rift valley fever virus interacts with pericentromeric DNA sequences of the host cell, inducing chromosome cohesion and segregation defects.

PubMed

Mansuroglu, Z; Josse, T; Gilleron, J; Billecocq, A; Leger, P; Bouloy, M; Bonnefoy, E

2010-01-01

Rift Valley fever virus (RVFV) is an emerging, highly pathogenic virus; RVFV infection can lead to encephalitis, retinitis, or fatal hepatitis associated with hemorrhagic fever in humans, as well as death, abortions, and fetal deformities in animals. RVFV nonstructural NSs protein, a major factor of the virulence, forms filamentous structures in the nuclei of infected cells. In order to further understand RVFV pathology, we investigated, by chromatin immunoprecipitation, immunofluorescence, fluorescence in situ hybridization, and confocal microscopy, the capacity of NSs to interact with the host genome. Our results demonstrate that even though cellular DNA is predominantly excluded from NSs filaments, NSs interacts with some specific DNA regions of the host genome such as clusters of pericentromeric gamma-satellite sequence. Targeting of these sequences by NSs was correlated with the induction of chromosome cohesion and segregation defects in RVFV-infected murine, as well as sheep cells. Using recombinant nonpathogenic virus rZHDeltaNSs210-230, expressing a NSs protein deleted of its region of interaction with cellular factor SAP30, we showed that the NSs-SAP30 interaction was essential for NSs to target pericentromeric sequences, as well as for induction of chromosome segregation defects. The effect of RVFV upon the inheritance of genetic information is discussed with respect to the pathology associated with fetal deformities and abortions, highlighting the main role played by cellular cofactor SAP30 on the establishment of NSs interactions with host DNA sequences and RVFV pathogenesis.

Rift valley fever virus infection of human cells and insect hosts is promoted by protein kinase C epsilon.

PubMed

Filone, Claire Marie; Hanna, Sheri L; Caino, M Cecilia; Bambina, Shelly; Doms, Robert W; Cherry, Sara

2010-11-24

As an arthropod-borne human pathogen, Rift Valley fever virus (RVFV) cycles between an insect vector and mammalian hosts. Little is known about the cellular requirements for infection in either host. Here we developed a tissue culture model for RVFV infection of human and insect cells that is amenable to high-throughput screening. Using this approach we screened a library of 1280 small molecules with pharmacologically defined activities and identified 59 drugs that inhibited RVFV infection with 15 inhibiting RVFV replication in both human and insect cells. Amongst the 15 inhibitors that blocked infection in both hosts was a subset that inhibits protein kinase C. Further studies found that infection is dependent upon the novel protein kinase C isozyme epsilon (PKCε) in both human and insect cells as well as in adult flies. Altogether, these data show that inhibition of cellular factors required for early steps in the infection cycle including PKCε can block RVFV infection, and may represent a starting point for the development of anti-RVFV therapeutics.

Discovery of Novel Viruses in Mosquitoes from the Zambezi Valley of Mozambique

PubMed Central

Hayer, Juliette; Abilio, Ana Paula; Mulandane, Fernando Chanisso; Verner-Carlsson, Jenny; Falk, Kerstin I.; Fafetine, Jose M.; Berg, Mikael; Blomström, Anne-Lie

2016-01-01

Mosquitoes carry a wide variety of viruses that can cause vector-borne infectious diseases and affect both human and veterinary public health. Although Mozambique can be considered a hot spot for emerging infectious diseases due to factors such as a rich vector population and a close vector/human/wildlife interface, the viral flora in mosquitoes have not previously been investigated. In this study, viral metagenomics was employed to analyze the viral communities in Culex and Mansonia mosquitoes in the Zambezia province of Mozambique. Among the 1.7 and 2.6 million sequences produced from the Culex and Mansonia samples, respectively, 3269 and 983 reads were classified as viral sequences. Viruses belonging to the Flaviviridae, Rhabdoviridae and Iflaviridae families were detected, and different unclassified single- and double-stranded RNA viruses were also identified. A near complete genome of a flavivirus, tentatively named Cuacua virus, was obtained from the Mansonia mosquitoes. Phylogenetic analysis of this flavivirus, using the NS5 amino acid sequence, showed that it grouped with ‘insect-specific’ viruses and was most closely related to Nakiwogo virus previously identified in Uganda. Both mosquito genera had viral sequences related to Rhabdoviruses, and these were most closely related to Culex tritaeniorhynchus rhabdovirus (CTRV). The results from this study suggest that several viruses specific for insects belonging to, for example, the Flaviviridae and Rhabdoviridae families, as well as a number of unclassified RNA viruses, are present in mosquitoes in Mozambique. PMID:27682810

Potency of a thermostabilised chimpanzee adenovirus Rift Valley Fever vaccine in cattle.

PubMed

Dulal, Pawan; Wright, Daniel; Ashfield, Rebecca; Hill, Adrian V S; Charleston, Bryan; Warimwe, George M

2016-04-29

Development of safe and efficacious vaccines whose potency is unaffected by long-term storage at ambient temperature would obviate major vaccine deployment hurdles and limit wastage associated with breaks in the vaccine cold chain. Here, we evaluated the immunogenicity of a novel chimpanzee adenovirus vectored Rift Valley Fever vaccine (ChAdOx1-GnGc) in cattle, following its thermostabilisation by slow desiccation on glass fiber membranes in the non-reducing sugars trehalose and sucrose. Thermostabilised ChAdOx1-GnGc vaccine stored for 6 months at 25, 37 or 45 ° C elicited comparable Rift Valley Fever virus neutralising antibody titres to those elicited by the 'cold chain' vaccine (stored at -80 ° C throughout) at the same dose, and these were within the range associated with protection against Rift Valley Fever in cattle. The results support the use of sugar-membrane thermostabilised vaccines in target livestock species. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

N-Glycans on the Rift Valley Fever Virus Envelope Glycoproteins Gn and Gc Redundantly Support Viral Infection via DC-SIGN

PubMed Central

Phoenix, Inaia; Nishiyama, Shoko; Lokugamage, Nandadeva; Hill, Terence E.; Huante, Matthew B.; Slack, Olga A.L.; Carpio, Victor H.; Freiberg, Alexander N.; Ikegami, Tetsuro

2016-01-01

Rift Valley fever is a mosquito-transmitted, zoonotic disease that infects humans and ruminants. Dendritic cell specific intercellular adhesion molecule 3 (ICAM-3) grabbing non-integrin (DC-SIGN) acts as a receptor for members of the phlebovirus genus. The Rift Valley fever virus (RVFV) glycoproteins (Gn/Gc) encode five putative N-glycan sequons (asparagine (N)–any amino acid (X)–serine (S)/threonine (T)) at positions: N438 (Gn), and N794, N829, N1035, and N1077 (Gc). The N-glycosylation profile and significance in viral infection via DC-SIGN have not been elucidated. Gc N-glycosylation was first evaluated by using Gc asparagine (N) to glutamine (Q) mutants. Subsequently, we generated a series of recombinant RVFV MP-12 strain mutants, which encode N-to-Q mutations, and the infectivity of each mutant in Jurkat cells stably expressing DC-SIGN was evaluated. Results showed that Gc N794, N1035, and N1077 were N-glycosylated but N829 was not. Gc N1077 was heterogeneously N-glycosylated. RVFV Gc made two distinct N-glycoforms: “Gc-large” and “Gc-small”, and N1077 was responsible for “Gc-large” band. RVFV showed increased infection of cells expressing DC-SIGN compared to cells lacking DC-SIGN. Infection via DC-SIGN was increased in the presence of either Gn N438 or Gc N1077. Our study showed that N-glycans on the Gc and Gn surface glycoproteins redundantly support RVFV infection via DC-SIGN. PMID:27223297

The effect of Tembusu virus infection in different week-old Cherry Valley breeding ducks.

PubMed

Lu, Yunjian; Dou, Yanguo; Ti, Jinfeng; Wang, Aihua; Cheng, Binghua; Zhang, Xin; Diao, Youxiang

2016-08-30

To study the effect of Tembusu virus (TMUV) infection on Cherry Valley Breeding ducks of different ages, 350 five-week-old ducks were divided into 14 groups. Ducks in seven experimental group were respectively infected with 1.265×10(5) mean embryo lethal dose (ELD50) of TMUV-AHQY strain (in 4.2mL) by intravenous route. Ducks in control groups were inoculated with Phosphate-buffered Saline (PBS) in the same way. Clinical symptoms, gross and microscopic lesions, viral loads and serum antibodies were detected and recorded for 20days after infection. Some ducks infected at 7 and 21 week s of age showed severe clinical symptoms including depression and inappetence, and no obvious clinical symptoms were seen in other week-old infected ducks. Severe gross lesions including hepatomegaly, meningeal congestion, myocardial hemorrhage, intestinal, myocardial and pulmonary edema were observed in ducks infected at 7, 18 and 21 weeks of age. No or mild gross lesions were observed in ducks infected at 14 and 16 weeks of age. The main microscopic lesions including hyperaemia, degeneration and necrosis of different cells and inflammatory cellular infiltration mainly consisting of mononuclear cells or lymphocytes were observed in ducks infected at 7 and 21 week of age. But relatively intact structures and rare lymphocytic infiltration were presented in ducks infected at 14 and 16 weeks of age. Viral antigen was more frequently observed in organ slices collected from 7 week-old infected ducks and few positive staining was found in 14 and 16 week-old infected ducks. Less viral loads in different tissues and swabs were detected by a quantitative real-time PCR assay. The level of viral loads in the tissues of ducks infected at 14 and 16 weeks of age was very lower than that of ducks infected at 7 and 21 weeks of age. Meanwhile, less viral copy numbers were detected in swab samples collected from 14 and 16 week-old infected ducks. Ducks infected at 14-week-old developed significantly

Blood meal analysis and virus detection in blood-fed mosquitoes collected during the 2006-2007 Rift Valley fever outbreak in Kenya.

PubMed

Lutomiah, Joel; Omondi, David; Masiga, Daniel; Mutai, Collins; Mireji, Paul O; Ongus, Juliette; Linthicum, Ken J; Sang, Rosemary

2014-09-01

Rift Valley fever (RVF) is a zoonosis of domestic ruminants in Africa. Blood-fed mosquitoes collected during the 2006-2007 RVF outbreak in Kenya were analyzed to determine the virus infection status and animal source of the blood meals. Blood meals from individual mosquito abdomens were screened for viruses using Vero cells and RT-PCR. DNA was also extracted and the cytochrome c oxidase 1 (CO1) and cytochrome b (cytb) genes amplified by PCR. Purified amplicons were sequenced and queried in GenBank and Barcode of Life Database (BOLD) to identify the putative blood meal sources. The predominant species in Garissa were Aedes ochraceus, (n=561, 76%) and Ae. mcintoshi, (n=176, 24%), and Mansonia uniformis, (n=24, 72.7%) in Baringo. Ae. ochraceus fed on goats (37.6%), cattle (16.4%), donkeys (10.7%), sheep (5.9%), and humans (5.3%). Ae. mcintoshi fed on the same animals in almost equal proportions. RVFV was isolated from Ae. ochraceus that had fed on sheep (4), goats (3), human (1), cattle (1), and unidentified host (1), with infection and dissemination rates of 1.8% (10/561) and 50% (5/10), respectively, and 0.56% (1/176) and 100% (1/1) in Ae. mcintoshi. In Baringo, Ma. uniformis fed on sheep (38%), frogs (13%), duikers (8%), cattle (4%), goats (4%), and unidentified hosts (29%), with infection and dissemination rates of 25% (6/24) and 83.3% (5/6), respectively. Ndumu virus (NDUV) was also isolated from Ae. ochraceus with infection and dissemination rates of 2.3% (13/561) and 76.9% (10/13), and Ae. mcintoshi, 2.8% (5/176) and 80% (4/5), respectively. Ten of the infected Ae. ochraceus had fed on goats, sheep (1), and unidentified hosts (2), and Ae. mcintoshi on goats (3), camel (1), and donkey (1). This study has demonstrated that RVFV and NDUV were concurrently circulating during the outbreak, and sheep and goats were the main amplifiers of these viruses respectively.

Epidemiologic and environmental risk factors of rift valley fever in southern Africa from 2008 to 2011

USDA-ARS?s Scientific Manuscript database

BACKGROUND: Rift Valley fever outbreaks have been associated with periods of widespread and above average rainfall over several months which allows for the virus infected mosquito vector populations to emerge and propagate. This has provided basis to develop complex models based on environmental fa...

Identification of central Kenyan Rift Valley Fever virus vector habitats with Landsat TM and evaluation of their flooding status with airborne imaging radar

NASA Technical Reports Server (NTRS)

Pope, K. O.; Sheffner, E. J.; Linthicum, K. J.; Bailey, C. L.; Logan, T. M.; Kasischke, E. S.; Birney, K.; Njogu, A. R.; Roberts, C. R.

1992-01-01

Rift Valley Fever (RVF) is a mosquito-borne virus that affects livestock and humans in Africa. Landsat TM data are shown to be effective in identifying dambos, intermittently flooded areas that are potential mosquite breeding sites, in an area north of Nairobi, Kenya. Positive results were obtained from a limited test of flood detection in dambos with airborne high resolution L, C, and X band multipolarization SAR imagery. L and C bands were effective in detecting flooded dambos, but LHH was by far the best channel for discrimination between flooded and nonflooded sites in both sedge and short-grass environments. This study demonstrates the feasibility of a combined passive and active remote sensing program for monitoring the location and condition of RVF vector habitats, thus making future control of the disease more promising.

Valley-dependent band structure and valley polarization in periodically modulated graphene

NASA Astrophysics Data System (ADS)

Lu, Wei-Tao

2016-08-01

The valley-dependent energy band and transport property of graphene under a periodic magnetic-strained field are studied, where the time-reversal symmetry is broken and the valley degeneracy is lifted. The considered superlattice is composed of two different barriers, providing more degrees of freedom for engineering the electronic structure. The electrons near the K and K' valleys are dominated by different effective superlattices. It is found that the energy bands for both valleys are symmetric with respect to ky=-(AM+ξ AS) /4 under the symmetric superlattices. More finite-energy Dirac points, more prominent collimation behavior, and new crossing points are found for K' valley. The degenerate miniband near the K valley splits into two subminibands and produces a new band gap under the asymmetric superlattices. The velocity for the K' valley is greatly renormalized compared with the K valley, and so we can achieve a finite velocity for the K valley while the velocity for the K' valley is zero. Especially, the miniband and band gap could be manipulated independently, leading to an increase of the conductance. The characteristics of the band structure are reflected in the transmission spectra. The Dirac points and the crossing points appear as pronounced peaks in transmission. A remarkable valley polarization is obtained which is robust to the disorder and can be controlled by the strain, the period, and the voltage.

Phenotypic Variation among Culex pipiens Complex (Diptera: Culicidae) Populations from the Sacramento Valley, California: Horizontal and Vertical Transmission of West Nile Virus, Diapause Potential, Autogeny, and Host Selection

PubMed Central

Nelms, Brittany M.; Kothera, Linda; Thiemann, Tara; Macedo, Paula A.; Savage, Harry M.; Reisen, William K.

2013-01-01

The vector competence and bionomics of Culex pipiens form pipiens L. and Cx. pipiens f. molestus Forskäl were evaluated for populations from the Sacramento Valley. Both f. pipiens and f. molestus females became infected, produced disseminated infections, and were able to transmit West Nile virus. Form molestus females also transmitted West Nile virus vertically to egg rafts and F1 progeny, whereas f. pipiens females only transmitted to egg rafts. Culex pipiens complex from urban Sacramento blood-fed on seven different avian species and two mammalian species. Structure analysis of blood-fed mosquitoes identified K = 4 genetic clusters: f. molestus, f. pipiens, a group of genetically similar hybrids (Cluster X), and admixed individuals. When females were exposed as larvae to midwinter conditions in bioenvironmental chambers, 85% (N = 79) of aboveground Cx. pipiens complex females and 100% (N = 34) of underground f. molestus females did not enter reproductive diapause. PMID:24043690

Serological Evidence of Rift Valley Fever Virus Circulation in Sheep and Goats in Zambézia Province, Mozambique

PubMed Central

Fafetine, José; Neves, Luis; Thompson, Peter N.; Paweska, Janusz T.; Rutten, Victor P. M. G.; Coetzer, J. A. W.

2013-01-01

Rift Valley fever (RVF) is endemic in most parts of Africa and has also been reported to occur in the Arabian Peninsula. It is responsible for significant morbidity and mortality, particularly in livestock, but also in humans. During the last two decades several outbreaks of RVF have been reported in countries in Southern Africa. In contrast to other countries, no clinical disease has been reported in Mozambique during this period. In a serological study conducted in 2007 in five districts of Zambézia Province, Mozambique, of a total of 654 small ruminants sampled (277 sheep and 377 goats), 35.8% of sheep sera and 21.2% of goat sera were positive for RVF virus (RVFV) antibodies in a virus neutralization test (VN) and in an IgG enzyme-linked immunosorbent assay (ELISA). In 2010, a cross-sectional survey was conducted in 313 sheep and 449 goats in two districts of the same province. This study revealed an overall seropositivity rate of 9.2% in sheep and 11.6% in goat and an increased likelihood of being seropositive in older animals (OR = 7.3; p<0.001) using an IgG ELISA. 29 out of 240 animals assessed for RVF specific IgM by ELISA were positive, suggesting recent exposure to RVFV. However, a longitudinal study carried out between September 2010 and April 2011 in a cohort of 125 of these animals (74 sheep and 51 goats) failed to demonstrate seroconversion. The results of the study indicate that RVFV circulates sub-clinically in domestic small ruminants in Zambézia Province. PMID:23469300

Planning for Rift Valley fever virus: Use of GIS to estimate the human health threat of white-tailed deer (Odocoileus virginianus)-related transmission

PubMed Central

Kakani, Sravan; LaBeaud, A. Desirée; King, Charles H.

2011-01-01

Rift Valley fever virus (RVFV) is a mosquito-borne phlebovirus of the Bunyaviridae family that causes frequent outbreaks of severe animal and human disease in sub-Saharan Africa, Egypt,and the Arabian Peninsula. Based on its many known competent vectors, its potential for transmission via aerosolization, and its progressive spread from East Africa to neighboring regions, RVFV is considered a high-priority, emerging health threat forhumans, livestock, and wildlife in all parts of the world. Introduction of West Nile virus to North America has shown the potential for ‘exotic’ viral pathogens to become embedded in local ecological systems. While RVFV is known to infect and amplify within domestic livestock, such as taurine cattle, sheep, and goats, if RVFV is accidentally or intentionally introduced into North America, an important unknown factor will be the role of local wildlife in the maintenance or propagation of virus transmission. We examined the potential impact of RVFV transmission via white-tailed deer (Odocoileus virginianus)in a typical northeastern United States urban-suburban landscape, where livestock are rare, but these potentially susceptible ungulate wildlife are highly abundant. Model results, based on overlap of mosquito, human, and projected deer densities, indicate that a significant proportion (497/1186 km2, or 42 %) of the urban and peri-urban landscape could be affected by RVFV transmission during the late summermonths. Deer population losses, either by intervention for herd reduction or by RVFV-related mortality, would substantially reduce these likely transmission zones to 53.1 km2, orby 89%. PMID:21080319

Transmission Dynamics of Rift Valley Fever Virus: Effects of Live and Killed Vaccines on Epizootic Outbreaks and Enzootic Maintenance

PubMed Central

Chamchod, Farida; Cosner, Chris; Cantrell, R. Stephen; Beier, John C.; Ruan, Shigui

2016-01-01

Rift Valley fever virus (RVFV) is an arthropod-borne viral pathogen that causes significant morbidity and mortality in small ruminants throughout Africa and the Middle East. Due to the sporadic and explosive nature of RVF outbreaks, vaccination has proved challenging to reduce RVFV infection in the ruminant population. Currently, there are two available types of vaccines, live and killed, in endemic areas. In this study, two mathematical models have been developed to explore the impact of live and killed vaccines on the transmission dynamics of RVFV. We demonstrate in general that vaccination helps reduce the severity of RVF outbreaks and that less delay in implementation and more vaccination attempts and effective vaccines can reduce the outbreak magnitude and the endemic number of RVFV. However, an introduction of a number of ruminants vaccinated by live vaccines in RVFV-free areas may cause an outbreak and RVFV may become endemic if there is sustained use of live vaccines. Other factors that are the important determinants of RVF outbreaks include: unsustained vaccination programs, recruitment of susceptible ruminants, and the seasonal abundance of mosquitoes. PMID:26869999

Rift Valley fever risk map model and seroprevalence in selected wild ungulates and camels from Kenya

USDA-ARS?s Scientific Manuscript database

Since the first isolation of Rift Valley fever virus (RVFV) in the 1930s, there have been multiple epizootics and epidemics in animals and humans in sub-Saharan Africa. Prospective climate-based models have recently been developed that flag areas at risk of RVFV transmission in endemic regions based...

Comprehensive Phylogenetic Reconstructions of Rift Valley Fever Virus: The 2010 Northern Mauritania Outbreak in the Camelus dromedarius Species

PubMed Central

Lo, Modou M.; Thiongane, Yaya; Diop, Mariame; Isselmou, Katia; Doumbia, Baba; Baba, Mohammed Ould; El Arbi, Ahmed S.; Lancelot, Renaud; Kane, Y.; Albina, Emmanuel; Cêtre-Sossah, Catherine

2014-01-01

Abstract Rift valley fever (RVF) is a mosquito-borne disease of domestic and wild ruminants caused by RVF virus (RVFV), a phlebovirus (Bunyaviridae). RVF is widespread in Sub-Saharan Africa. In September of 2010, an RVF outbreak occurred in northern Mauritania involving mass abortions in small ruminants and camels (Camelus dromedarius) and at least 63 human clinical cases, including 13 deaths. In camels, serological prevalence was 27.5–38.5% (95% confidence interval, n=279). For the first time, clinical signs other than abortions were reported in this species, including hemorrhagic septicemia and severe respiratory distress in animals. We assessed the presence of RVFV in camel sera sampled during this outbreak and generated whole-genome sequences of RVFV to determine the possible origin of this RVFV strain. Phylogenetic analyses suggested a shared ancestor between the Mauritania 2010 strain and strains from Zimbabwe (2269, 763, and 2373), Kenya (155_57 and 56IB8), South Africa (Kakamas, SA75 and SA51VanWyck), Uganda (Entebbe), and other strains linked to the 1987 outbreak of RVF in Mauritania (OS1, OS3, OS8, and OS9). PMID:25514121

Comprehensive phylogenetic reconstructions of Rift Valley fever virus: the 2010 northern Mauritania outbreak in the Camelus dromedarius species.

PubMed

El Mamy, Ahmed B; Lo, Modou M; Thiongane, Yaya; Diop, Mariame; Isselmou, Katia; Doumbia, Baba; Baba, Mohammed Ould; El Arbi, Ahmed S; Lancelot, Renaud; Kane, Y; Albina, Emmanuel; Cêtre-Sossah, Catherine

2014-12-01

Rift valley fever (RVF) is a mosquito-borne disease of domestic and wild ruminants caused by RVF virus (RVFV), a phlebovirus (Bunyaviridae). RVF is widespread in Sub-Saharan Africa. In September of 2010, an RVF outbreak occurred in northern Mauritania involving mass abortions in small ruminants and camels (Camelus dromedarius) and at least 63 human clinical cases, including 13 deaths. In camels, serological prevalence was 27.5-38.5% (95% confidence interval, n=279). For the first time, clinical signs other than abortions were reported in this species, including hemorrhagic septicemia and severe respiratory distress in animals. We assessed the presence of RVFV in camel sera sampled during this outbreak and generated whole-genome sequences of RVFV to determine the possible origin of this RVFV strain. Phylogenetic analyses suggested a shared ancestor between the Mauritania 2010 strain and strains from Zimbabwe (2269, 763, and 2373), Kenya (155_57 and 56IB8), South Africa (Kakamas, SA75 and SA51VanWyck), Uganda (Entebbe), and other strains linked to the 1987 outbreak of RVF in Mauritania (OS1, OS3, OS8, and OS9).

The Rift Valley fever: could re-emerge in Egypt again?

PubMed

El-Bahnasawy, Mamdouh; Megahed, Laila Abdel-Mawla; Abdalla Saleh, Hala Ahmed; Morsy, Tosson A

2013-04-01

The Rift Valley fever (RVF) is a neglected, emerging, mosquito-borne disease with severe negative impact on human and animal health and economy. RVF is caused by RVF virus of the family of Bunyaviridae, genus Phlebovirus. RVF is an acute, febrile disease affecting humans and a wide range of animals. The virus is trans-mitted through the bites from mosquitoes and exposure to viremic blood, body fluids, or contact with tissues of infected animals or by inhaling natural virus aerosols, also possibly by consumption of infected unpasteurized milk. The RVF-virus replicate at the site introduction and in local lymphatic followed by viremia and spread to other organs as the liver and central nervous system, causing the hepatic necrosis and eosinophilia cytoplasmic degeneration. The main signs and symptoms are fever, headache, myalgia, arthralgia, photophobia, bradycardia, conjunctivitis and flushing face. Main complications include jaundice, hemorrhagic, meningoencephalitis and retinal lesions. Generally speaking, in the 21st Century, the vector-borne infectious diseases, was accepted as the disaster issues with the considerable significant morbidity and mortality. These facts should be considered by the public health, veterinary and agricultural authorities

West Nile Virus Range Expansion into British Columbia

PubMed Central

Henry, Bonnie; Mak, Sunny; Fraser, Mieke; Taylor, Marsha; Li, Min; Cooper, Ken; Furnell, Allen; Wong, Quantine; Morshed, Muhammad

2010-01-01

In 2009, an expansion of West Nile virus (WNV) into the Canadian province of British Columbia was detected. Two locally acquired cases of infection in humans and 3 cases of infection in horses were detected by ELISA and plaque-reduction neutralization tests. Ten positive mosquito pools were detected by reverse transcription PCR. Most WNV activity in British Columbia in 2009 occurred in the hot and dry southern Okanagan Valley. Virus establishment and amplification in this region was likely facilitated by above average nightly temperatures and a rapid accumulation of degree-days in late summer. Estimated exposure dates for humans and initial detection of WNV-positive mosquitoes occurred concurrently with a late summer increase in Culex tarsalis mosquitoes (which spread western equine encephalitis) in the southern Okanagan Valley. The conditions present during this range expansion suggest that temperature and Cx. tarsalis mosquito abundance may be limiting factors for WNV transmission in this portion of the Pacific Northwest. PMID:20678319

Mutational Analysis of the Rift Valley Fever Virus Glycoprotein Precursor Proteins for Gn Protein Expression

PubMed Central

Phoenix, Inaia; Lokugamage, Nandadeva; Nishiyama, Shoko; Ikegami, Tetsuro

2016-01-01

The Rift Valley fever virus (RVFV) M-segment encodes the 78 kD, NSm, Gn, and Gc proteins. The 1st AUG generates the 78 kD-Gc precursor, the 2nd AUG generates the NSm-Gn-Gc precursor, and the 3rd AUG makes the NSm’-Gn-Gc precursor. To understand biological changes due to abolishment of the precursors, we quantitatively measured Gn secretion using a reporter assay, in which a Gaussia luciferase (gLuc) protein is fused to the RVFV M-segment pre-Gn region. Using the reporter assay, the relative expression of Gn/gLuc fusion proteins was analyzed among various AUG mutants. The reporter assay showed efficient secretion of Gn/gLuc protein from the precursor made from the 2nd AUG, while the removal of the untranslated region upstream of the 2nd AUG (AUG2-M) increased the secretion of the Gn/gLuc protein. Subsequently, recombinant MP-12 strains encoding mutations in the pre-Gn region were rescued, and virological phenotypes were characterized. Recombinant MP-12 encoding the AUG2-M mutation replicated slightly less efficiently than the control, indicating that viral replication is further influenced by the biological processes occurring after Gn expression, rather than the Gn abundance. This study showed that, not only the abolishment of AUG, but also the truncation of viral UTR, affects the expression of Gn protein by the RVFV M-segment. PMID:27231931

Mutational Analysis of the Rift Valley Fever Virus Glycoprotein Precursor Proteins for Gn Protein Expression.

PubMed

Phoenix, Inaia; Lokugamage, Nandadeva; Nishiyama, Shoko; Ikegami, Tetsuro

2016-05-24

The Rift Valley fever virus (RVFV) M-segment encodes the 78 kD, NSm, Gn, and Gc proteins. The 1st AUG generates the 78 kD-Gc precursor, the 2nd AUG generates the NSm-Gn-Gc precursor, and the 3rd AUG makes the NSm'-Gn-Gc precursor. To understand biological changes due to abolishment of the precursors, we quantitatively measured Gn secretion using a reporter assay, in which a Gaussia luciferase (gLuc) protein is fused to the RVFV M-segment pre-Gn region. Using the reporter assay, the relative expression of Gn/gLuc fusion proteins was analyzed among various AUG mutants. The reporter assay showed efficient secretion of Gn/gLuc protein from the precursor made from the 2nd AUG, while the removal of the untranslated region upstream of the 2nd AUG (AUG2-M) increased the secretion of the Gn/gLuc protein. Subsequently, recombinant MP-12 strains encoding mutations in the pre-Gn region were rescued, and virological phenotypes were characterized. Recombinant MP-12 encoding the AUG2-M mutation replicated slightly less efficiently than the control, indicating that viral replication is further influenced by the biological processes occurring after Gn expression, rather than the Gn abundance. This study showed that, not only the abolishment of AUG, but also the truncation of viral UTR, affects the expression of Gn protein by the RVFV M-segment.

Rift Valley fever virus: Unanswered questions.

PubMed

Bird, Brian H; McElroy, Anita K

2016-08-01

This mosquito-borne pathogen of humans and animals respects no international or geographic boundaries. It is currently found in parts of Africa and the Arabian Peninsula where periodic outbreaks of severe and fatal disease occur, and threatens to spread into other geographic regions. In recent years, modern molecular techniques have led to many breakthroughs deepening our understanding of the mechanisms of RVFV virulence, phylogenetics, and the creation of several next-generation vaccine candidates. Despite tremendous progress in these areas, other challenges remain in RVF disease pathogenesis, the virus life-cycle, and outbreak response preparedness that deserve our attention. Here we discuss and highlight ten key knowledge gaps and challenges in RVFV research. Answers to these key questions may lead to the development of new effective therapeutics and enhanced control strategies for this serious human and veterinary health threat. Published by Elsevier B.V.

NSs protein of rift valley fever virus promotes posttranslational downregulation of the TFIIH subunit p62.

PubMed

Kalveram, Birte; Lihoradova, Olga; Ikegami, Tetsuro

2011-07-01

Rift Valley fever virus (RVFV; family Bunyaviridae, genus Phlebovirus) is an important emerging pathogen of humans and ruminants. Its NSs protein has previously been identified as a major virulence factor that suppresses host defense through three distinct mechanisms: it directly inhibits beta interferon (IFN-β) promoter activity, it promotes the degradation of double-stranded RNA-dependent protein kinase (PKR), and it suppresses host transcription by disrupting the assembly of the basal transcription factor TFIIH through sequestration of its p44 subunit. Here, we report that in addition to PKR, NSs also promotes the degradation of the TFIIH subunit p62. Infection of cells with the RVFV MP-12 vaccine strain reduced p62 protein levels to below the detection limit early in the course of infection. This NSs-mediated downregulation of p62 was posttranslational, as it was unaffected by pharmacological inhibition of transcription or translation and MP-12 infection had no effect on p62 mRNA levels. Treatment of cells with proteasome inhibitors but not inhibition of lysosomal acidification or nuclear export resulted in a stabilization of p62 in the presence of NSs. Furthermore, p62 could be coprecipitated with NSs from lysates of infected cells. These data suggest that the RVFV NSs protein is able to interact with the TFIIH subunit p62 inside infected cells and promotes its degradation, which can occur directly in the nucleus.

Sorafenib Impedes Rift Valley Fever Virus Egress by Inhibiting Valosin-Containing Protein Function in the Cellular Secretory Pathway.

PubMed

Brahms, Ashwini; Mudhasani, Rajini; Pinkham, Chelsea; Kota, Krishna; Nasar, Farooq; Zamani, Rouzbeh; Bavari, Sina; Kehn-Hall, Kylene

2017-11-01

There is an urgent need for therapeutic development to combat infections caused by Rift Valley fever virus (RVFV), which causes devastating disease in both humans and animals. In an effort to repurpose drugs for RVFV treatment, our previous studies screened a library of FDA-approved drugs. The most promising candidate identified was the hepatocellular and renal cell carcinoma drug sorafenib. Mechanism-of-action studies indicated that sorafenib targeted a late stage in virus infection and caused a buildup of virions within cells. In addition, small interfering RNA (siRNA) knockdown studies suggested that nonclassical targets of sorafenib are important for the propagation of RVFV. Here we extend our previous findings to identify the mechanism by which sorafenib inhibits the release of RVFV virions from the cell. Confocal microscopy imaging revealed that glycoprotein Gn colocalizes and accumulates within the endoplasmic reticulum (ER) and the transport of Gn from the Golgi complex to the host cell membrane is reduced. Transmission electron microscopy demonstrated that sorafenib caused virions to be present inside large vacuoles inside the cells. p97/valosin-containing protein (VCP), which is involved in membrane remodeling in the secretory pathway and a known target of sorafenib, was found to be important for RVFV egress. Knockdown of VCP resulted in decreased RVFV replication, reduced Gn Golgi complex localization, and increased Gn ER accumulation. The intracellular accumulation of RVFV virions was also observed in cells transfected with siRNA targeting VCP. Collectively, these data indicate that sorafenib causes a disruption in viral egress by targeting VCP and the secretory pathway, resulting in a buildup of virions within dilated ER vesicles. IMPORTANCE In humans, symptoms of RVFV infection mainly include a self-limiting febrile illness. However, in some cases, infected individuals can also experience hemorrhagic fever, neurological disorders, liver failure, and

Drivers of Rift Valley fever epidemics in Madagascar.

PubMed

Lancelot, Renaud; Béral, Marina; Rakotoharinome, Vincent Michel; Andriamandimby, Soa-Fy; Héraud, Jean-Michel; Coste, Caroline; Apolloni, Andrea; Squarzoni-Diaw, Cécile; de La Rocque, Stéphane; Formenty, Pierre B H; Bouyer, Jérémy; Wint, G R William; Cardinale, Eric

2017-01-31

Rift Valley fever (RVF) is a vector-borne viral disease widespread in Africa. The primary cycle involves mosquitoes and wild and domestic ruminant hosts. Humans are usually contaminated after contact with infected ruminants. As many environmental, agricultural, epidemiological, and anthropogenic factors are implicated in RVF spread, the multidisciplinary One Health approach was needed to identify the drivers of RVF epidemics in Madagascar. We examined the environmental patterns associated with these epidemics, comparing human and ruminant serological data with environmental and cattle-trade data. In contrast to East Africa, environmental drivers did not trigger the epidemics: They only modulated local Rift Valley fever virus (RVFV) transmission in ruminants. Instead, RVFV was introduced through ruminant trade and subsequent movement of cattle between trade hubs caused its long-distance spread within the country. Contact with cattle brought in from infected districts was associated with higher infection risk in slaughterhouse workers. The finding that anthropogenic rather than environmental factors are the main drivers of RVF infection in humans can be used to design better prevention and early detection in the case of RVF resurgence in the region.

Inter-epidemic abundance and distribution of potential mosquito vectors for Rift Valley fever virus in Ngorongoro district, Tanzania.

PubMed

Mweya, Clement N; Kimera, Sharadhuli I; Mellau, Lesakit S B; Mboera, Leonard E G

2015-01-01

Rift Valley fever (RVF) is a mosquito-borne viral zoonosis that primarily affects ruminants but also has the capacity to infect humans. To determine the abundance and distribution of mosquito vectors in relation to their potential role in the virus transmission and maintenance in disease epidemic areas of Ngorongoro district in northern Tanzania. A cross-sectional entomological investigation was carried out before the suspected RVF outbreak in October 2012. Mosquitoes were sampled both outdoors and indoors using the Centre for Disease Control (CDC) light traps and Mosquito Magnets baited with attractants. Outdoor traps were placed in proximity with breeding sites and under canopy in banana plantations close to the sleeping places of animals. A total of 1,823 mosquitoes were collected, of which 87% (N=1,588) were Culex pipiens complex, 12% (N=226) Aedes aegypti, and 0.5% (N=9) Anopheles species. About two-thirds (67%; N=1,095) of C. pipiens complex and nearly 100% (N=225) of A. aegypti were trapped outdoors using Mosquito Magnets. All Anopheles species were trapped indoors using CDC light traps. There were variations in abundance of C. pipiens complex and A. aegypti among different ecological and vegetation habitats. Over three quarters (78%) of C. pipiens complex and most (85%) of the A. aegypti were trapped in banana and maize farms. Both C. pipiens complex and A. aegypti were more abundant in proximity with cattle and in semi-arid thorn bushes and lower Afro-montane. The highest number of mosquitoes was recorded in villages that were most affected during the RVF epidemic of 2007. Of the tested 150 pools of C. pipiens complex and 45 pools of A. aegypti, none was infected with RVF virus. These results provide insights into unique habitat characterisation relating to mosquito abundances and distribution in RVF epidemic-prone areas of Ngorongoro district in northern Tanzania.

Rift Valley Fever: An Emerging Mosquito-Borne Disease.

PubMed

Linthicum, Kenneth J; Britch, Seth C; Anyamba, Assaf

2016-01-01

Rift Valley fever (RVF), an emerging mosquito-borne zoonotic infectious viral disease caused by the RVF virus (RVFV) (Bunyaviridae: Phlebovirus), presents significant threats to global public health and agriculture in Africa and the Middle East. RVFV is listed as a select agent with significant potential for international spread and use in bioterrorism. RVFV has caused large, devastating periodic epizootics and epidemics in Africa over the past ∼60 years, with severe economic and nutritional impacts on humans from illness and livestock loss. In the past 15 years alone, RVFV caused tens of thousands of human cases, hundreds of human deaths, and more than 100,000 domestic animal deaths. Cattle, sheep, goats, and camels are particularly susceptible to RVF and serve as amplifying hosts for the virus. This review highlights recent research on RVF, focusing on vectors and their ecology, transmission dynamics, and use of environmental and climate data to predict disease outbreaks. Important directions for future research are also discussed.

Rift Valley fever outbreak--Kenya, November 2006-January 2007.

PubMed

2007-02-02

In mid-December 2006, several unexplained fatalities associated with fever and generalized bleeding were reported to the Kenya Ministry of Health (KMOH) from Garissa District in North Eastern Province (NEP). By December 20, a total of 11 deaths had been reported. Of serum samples collected from the first 19 patients, Rift Valley fever (RVF) virus RNA or immunoglobulin M (IgM) antibodies against RVF virus were found in samples from 10 patients; all serum specimens were negative for yellow fever, Ebola, Crimean-Congo hemorrhagic fever, and dengue viruses. The outbreak was confirmed by isolation of RVF virus from six of the specimens. Humans can be infected with RVF virus from bites of mosquitoes or other arthropod vectors that have fed on animals infected with RVF virus, or through contact with viremic animals, particularly livestock. Reports of livestock deaths and unexplained animal abortions in NEP provided further evidence of an RVF outbreak. On December 20, an investigation was launched by KMOH, the Kenya Field Epidemiology and Laboratory Training Program (FELTP), the Kenya Medical Research Institute (KEMRI), the Walter Reed Project of the U.S. Army Medical Research Unit, CDC-Kenya's Global Disease Detection Center, and other partners, including the World Health Organization (WHO) and Médecins Sans Frontières (MSF). This report describes the findings from that initial investigation and the control measures taken in response to the RVF outbreak, which spread to multiple additional provinces and districts, resulting in 404 cases with 118 deaths as of January 25, 2007.

The First Isolation and Whole Genome Sequencing of Murray Valley Encephalitis Virus from Cerebrospinal Fluid of a Patient with Encephalitis.

PubMed

Russell, Jessica S; Caly, Leon; Kostecki, Renata; McGuinness, Sarah L; Carter, Glen; Bulach, Dieter; Seemann, Torsten; Stinear, Tim P; Baird, Rob; Catton, Mike; Druce, Julian

2018-06-11

Murray Valley Encephalitis virus (MVEV) is a mosquito-borne Flavivirus. Clinical presentation is rare but severe, with a case fatality rate of 15⁻30%. Here we report a case of MVEV from the cerebrospinal fluid (CSF) of a patient in the Northern Territory in Australia. Initial diagnosis was performed using both MVEV-specific real-time, and Pan- Flavivirus conventional, Polymerase Chain Reaction (PCR), with confirmation by Sanger sequencing. Subsequent isolation, the first from CSF, was conducted in Vero cells and the observed cytopathic effect was confirmed by increasing viral titre in the real-time PCR. Isolation allowed for full genome sequencing using the Scriptseq V2 RNASeq library preparation kit. A consensus genome for VIDRL-MVE was generated and phylogenetic analysis identified it as Genotype 2. This is the first reported isolation, and full genome sequencing of MVEV from CSF. It is also the first time Genotype 2 has been identified in humans. As such, this case has significant implications for public health surveillance, epidemiology, and the understanding of MVEV evolution.

Usutu virus: an emerging flavivirus in Europe.

PubMed

Ashraf, Usama; Ye, Jing; Ruan, Xindi; Wan, Shengfeng; Zhu, Bibo; Cao, Shengbo

2015-01-19

Usutu virus (USUV) is an African mosquito-borne flavivirus belonging to the Japanese encephalitis virus serocomplex. USUV is closely related to Murray Valley encephalitis virus, Japanese encephalitis virus, and West Nile virus. USUV was discovered in South Africa in 1959. In Europe, the first true demonstration of circulation of USUV was reported in Austria in 2001 with a significant die-off of Eurasian blackbirds. In the subsequent years, USUV expanded to neighboring countries, including Italy, Germany, Spain, Hungary, Switzerland, Poland, England, Czech Republic, Greece, and Belgium, where it caused unusual mortality in birds. In 2009, the first two human cases of USUV infection in Europe have been reported in Italy, causing meningoencephalitis in immunocompromised patients. This review describes USUV in terms of its life cycle, USUV surveillance from Africa to Europe, human cases, its cellular tropism and pathogenesis, its genetic relationship with other flaviviruses, genetic diversity among USUV strains, its diagnosis, and a discussion of the potential future threat to Asian countries.

77 FR 33237 - Saline Valley Warm Springs Management Plan/Environmental Impact Statement, Death Valley National...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-05

... Valley Warm Springs Management Plan/Environmental Impact Statement, Death Valley National Park, Inyo... an Environmental Impact Statement for the Saline Valley Warm Springs Management Plan, Death Valley... analysis process for the Saline Valley Warm Springs Management Plan for Death Valley [[Page 33238...

Emerging Infections of CNS: Avian Influenza A Virus, Rift Valley Fever Virus and Human Parechovirus.

PubMed

Wiley, Clayton A; Bhardwaj, Nitin; Ross, Ted M; Bissel, Stephanie J

2015-09-01

History is replete with emergent pandemic infections that have decimated the human population. Given the shear mass of humans that now crowd the earth, there is every reason to suspect history will repeat itself. We describe three RNA viruses that have recently emerged in the human population to mediate severe neurological disease. These new diseases are results of new mutations in the infectious agents or new exposure pathways to the agents or both. To appreciate their pathogenesis, we summarize the essential virology and immune response to each agent. Infection is described in the context of known host defenses. Once the viruses evade immune defenses and enter central nervous system (CNS) cells, they rapidly co-opt host RNA processing to a cataclysmic extent. It is not clear why the brain is particularly susceptible to RNA viruses; but perhaps because of its tremendous dependence on RNA processing for physiological functioning, classical mechanisms of host defense (eg, interferon disruption of viral replication) are diminished or not available. Effectiveness of immunity, immunization and pharmacological therapies is reviewed to contextualize the scope of the public health challenge. Unfortunately, vaccines that confer protection from systemic disease do not necessarily confer protection for the brain after exposure through unconventional routes. © 2015 International Society of Neuropathology.

Functional analysis of Rift Valley fever virus NSs encoding a partial truncation.

PubMed

Head, Jennifer A; Kalveram, Birte; Ikegami, Tetsuro

2012-01-01

Rift Valley fever virus (RVFV), belongs to genus Phlebovirus of the family Bunyaviridae, causes high rates of abortion and fetal malformation in infected ruminants as well as causing neurological disorders, blindness, or lethal hemorrhagic fever in humans. RVFV is classified as a category A priority pathogen and a select agent in the U.S., and currently there are no therapeutics available for RVF patients. NSs protein, a major virulence factor of RVFV, inhibits host transcription including interferon (IFN)-β mRNA synthesis and promotes degradation of dsRNA-dependent protein kinase (PKR). NSs self-associates at the C-terminus 17 aa., while NSs at aa.210-230 binds to Sin3A-associated protein (SAP30) to inhibit the activation of IFN-β promoter. Thus, we hypothesize that NSs function(s) can be abolished by truncation of specific domains, and co-expression of nonfunctional NSs with intact NSs will result in the attenuation of NSs function by dominant-negative effect. Unexpectedly, we found that RVFV NSs truncated at aa. 6-30, 31-55, 56-80, 81-105, 106-130, 131-155, 156-180, 181-205, 206-230, 231-248 or 249-265 lack functions of IFN-β mRNA synthesis inhibition and degradation of PKR. Truncated NSs were less stable in infected cells, while nuclear localization was inhibited in NSs lacking either of aa.81-105, 106-130, 131-155, 156-180, 181-205, 206-230 or 231-248. Furthermore, none of truncated NSs had exhibited significant dominant-negative functions for NSs-mediated IFN-β suppression or PKR degradation upon co-expression in cells infected with RVFV. We also found that any of truncated NSs except for intact NSs does not interact with RVFV NSs even in the presence of intact C-terminus self-association domain. Our results suggest that conformational integrity of NSs is important for the stability, cellular localization and biological functions of RVFV NSs, and the co-expression of truncated NSs does not exhibit dominant-negative phenotype.

27 CFR 9.57 - Green Valley of Russian River Valley.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Green Valley of Russian River Valley. 9.57 Section 9.57 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL AMERICAN VITICULTURAL AREAS Approved American Viticultural Areas § 9.57 Green Valley of Russian River...

27 CFR 9.57 - Green Valley of Russian River Valley.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Green Valley of Russian River Valley. 9.57 Section 9.57 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS AMERICAN VITICULTURAL AREAS Approved American Viticultural Areas § 9.57 Green Valley of Russian River...

27 CFR 9.57 - Green Valley of Russian River Valley.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Green Valley of Russian River Valley. 9.57 Section 9.57 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS AMERICAN VITICULTURAL AREAS Approved American Viticultural Areas § 9.57 Green Valley of Russian River...

27 CFR 9.57 - Green Valley of Russian River Valley.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Green Valley of Russian River Valley. 9.57 Section 9.57 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS AMERICAN VITICULTURAL AREAS Approved American Viticultural Areas § 9.57 Green Valley of Russian River...

27 CFR 9.57 - Green Valley of Russian River Valley.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Green Valley of Russian River Valley. 9.57 Section 9.57 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL AMERICAN VITICULTURAL AREAS Approved American Viticultural Areas § 9.57 Green Valley of Russian River...

Mosquito host choices on livestock amplifiers of Rift Valley fever virus in Kenya

USDA-ARS?s Scientific Manuscript database

Animal hosts may vary in their attraction and acceptability as components of the host location process for assessing biting rates of vectors and risk of exposure to pathogens. However, these parameters remain poorly understood for mosquito vectors of the Rift Valley fever (RVF), an arboviral disease...

Rift Valley fever virus NSs inhibits host transcription independently of the degradation of dsRNA-dependent Protein Kinase PKR

PubMed Central

Kalveram, Birte; Lihoradova, Olga; Indran, Sabarish V.; Lokugamage, Nandadeva; Head, Jennifer A.; Ikegami, Tetsuro

2012-01-01

Rift Valley fever virus (RVFV) encodes one major virulence factor, the NSs protein. NSs suppresses host general transcription, including interferon (IFN)-β mRNA synthesis, and promotes degradation of the dsRNA-dependent protein kinase (PKR). We generated a novel RVFV mutant (rMP12-NSsR173A) specifically lacking the function to promote PKR degradation. rMP12-NSsR173A infection induces early phosphorylation of eIF2α through PKR activation, while retaining the function to inhibit host general transcription including IFN-β gene inhibition. MP-12 NSs but not R173A NSs binds to wt PKR. R173A NSs formed filamentous structure in nucleus in a mosaic pattern, which was distinct from MP-12 NSs filament pattern. Due to early phosphorylation of eIF2α, rMP12-NSsR173A could not efficiently accumulate viral proteins. Our results suggest that NSs-mediated host general transcription suppression occurs independently of PKR degradation, while the PKR degradation is important to inhibit the phosphorylation of eIF2α in infected cells undergoing host general transcription suppression. PMID:23063407

Rift Valley fever virus NSs inhibits host transcription independently of the degradation of dsRNA-dependent protein kinase PKR.

PubMed

Kalveram, Birte; Lihoradova, Olga; Indran, Sabarish V; Lokugamage, Nandadeva; Head, Jennifer A; Ikegami, Tetsuro

2013-01-20

Rift Valley fever virus (RVFV) encodes one major virulence factor, the NSs protein. NSs suppresses host general transcription, including interferon (IFN)-β mRNA synthesis, and promotes degradation of the dsRNA-dependent protein kinase (PKR). We generated a novel RVFV mutant (rMP12-NSsR173A) specifically lacking the function to promote PKR degradation. rMP12-NSsR173A infection induces early phosphorylation of eIF2α through PKR activation, while retaining the function to inhibit host general transcription including IFN-β gene inhibition. MP-12 NSs but not R173A NSs binds to wt PKR. R173A NSs formed filamentous structure in nucleus in a mosaic pattern, which was distinct from MP-12 NSs filament pattern. Due to early phosphorylation of eIF2α, rMP12-NSsR173A could not efficiently accumulate viral proteins. Our results suggest that NSs-mediated host general transcription suppression occurs independently of PKR degradation, while the PKR degradation is important to inhibit the phosphorylation of eIF2α in infected cells undergoing host general transcription suppression. Copyright © 2012 Elsevier Inc. All rights reserved.

Development of a broad-spectrum antiviral with activity against Ebola virus.

PubMed

Aman, M Javad; Kinch, Michael S; Warfield, Kelly; Warren, Travis; Yunus, Abdul; Enterlein, Sven; Stavale, Eric; Wang, Peifang; Chang, Shaojing; Tang, Qingsong; Porter, Kevin; Goldblatt, Michael; Bavari, Sina

2009-09-01

We report herein the identification of a small molecule therapeutic, FGI-106, which displays potent and broad-spectrum inhibition of lethal viral hemorrhagic fevers pathogens, including Ebola, Rift Valley and Dengue Fever viruses, in cell-based assays. Using mouse models of Ebola virus, we further demonstrate that FGI-106 can protect animals from an otherwise lethal infection when used either in a prophylactic or therapeutic setting. A single treatment, administered 1 day after infection, is sufficient to protect animals from lethal Ebola virus challenge. Cell-based assays also identified inhibitory activity against divergent virus families, which supports a hypothesis that FGI-106 interferes with a common pathway utilized by different viruses. These findings suggest FGI-106 may provide an opportunity for targeting viral diseases.

Seroprevalence of Hepatitis B and C Infections among Healthy Volunteer Blood Donors in the Central California Valley.

PubMed

Sheikh, Muhammad Y; Atla, Pradeep R; Ameer, Adnan; Sadiq, Humaira; Sadler, Patrick C

2013-01-01

The Central California Valley has a diverse population with significant proportions of Hispanics and Asians. This cross-sectional study was conducted to evaluate the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) in healthy blood donors in the Valley. A total of 217,738 voluntary blood donors were identified between 2006 and 2010 (36,795 first-time donors; 180,943 repeat donors). Among the first-time donors, the HBV and HCV prevalence was 0.28% and 0.52%, respectively. Higher HBV prevalence seen in Asians (3%) followed by Caucasians (0.05%), African Americans (0.15%), and Hispanics (0.05%). Hmong had a HBV prevalence of 7.63% with a peak prevalence of 8.76% among the 16- to 35-year-old age group. Highest HCV prevalence in Native Americans (2.8) followed by Caucasians (0.59%), Hispanics (0.45%), African Americans (0.38%), and Asians (0.2%). Ethnic disparities persist with regard to the prevalence of HBV and HCV in the Central California Valley. The reported prevalence may be an underestimate because our study enrolled healthy volunteer blood donors only. The development of aggressive public health measures to evaluate the true prevalence of HBV and HCV and to identify those in need of HBV and HCV prevention measures and therapy is critically important.

Seroprevalence of Hepatitis B and C Infections among Healthy Volunteer Blood Donors in the Central California Valley

PubMed Central

Atla, Pradeep R.; Ameer, Adnan; Sadiq, Humaira; Sadler, Patrick C.

2013-01-01

Background/Aims The Central California Valley has a diverse population with significant proportions of Hispanics and Asians. This cross-sectional study was conducted to evaluate the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) in healthy blood donors in the Valley. Methods A total of 217,738 voluntary blood donors were identified between 2006 and 2010 (36,795 first-time donors; 180,943 repeat donors). Results Among the first-time donors, the HBV and HCV prevalence was 0.28% and 0.52%, respectively. Higher HBV prevalence seen in Asians (3%) followed by Caucasians (0.05%), African Americans (0.15%), and Hispanics (0.05%). Hmong had a HBV prevalence of 7.63% with a peak prevalence of 8.76% among the 16- to 35-year-old age group. Highest HCV prevalence in Native Americans (2.8) followed by Caucasians (0.59%), Hispanics (0.45%), African Americans (0.38%), and Asians (0.2%). Conclusions Ethnic disparities persist with regard to the prevalence of HBV and HCV in the Central California Valley. The reported prevalence may be an underestimate because our study enrolled healthy volunteer blood donors only. The development of aggressive public health measures to evaluate the true prevalence of HBV and HCV and to identify those in need of HBV and HCV prevention measures and therapy is critically important. PMID:23423771

Morphology of large valleys on Hawaii - Evidence for groundwater sapping and comparisons with Martian valleys

NASA Technical Reports Server (NTRS)

Kochel, R. Craig; Piper, Jonathan F.

1986-01-01

Morphometric data on the runoff and sapping valleys on the slopes of Hawaii and Molokai in Hawaii are analyzed. The analysis reveals a clear distinction between the runoff valleys and sapping valleys. The Hawaiian sapping valleys are characterized by: (1) steep valley walls and flat floors, (2) amphitheater heads, (3) low drainage density, (4) paucity of downstream tributaries, (5) low frequency of up-dip tributaries, and (6) structural and stratigraphic control on valley patterns. The characteristics of the Hawaiian sapping valleys are compared to Martian valleys and experimental systems, and good correlation between the data is detected. Flume experiments were also conducted to study the evolution of sapping valleys in response to variable structure and stratigraphy.

Evaluation of the Efficacy, Potential for Vector Transmission, and Duration of Immunity of MP-12, an Attenuated Rift Valley Fever Virus Vaccine Candidate, in Sheep

PubMed Central

Bennett, Kristine E.; Drolet, Barbara S.; Lindsay, Robbin; Mecham, James O.; Reeves, Will K.; Weingartl, Hana M.; Wilson, William C.

2015-01-01

Rift Valley fever virus (RVFV) causes serious disease in ruminants and humans in Africa. In North America, there are susceptible ruminant hosts and competent mosquito vectors, yet there are no fully licensed animal vaccines for this arthropod-borne virus, should it be introduced. Studies in sheep and cattle have found the attenuated strain of RVFV, MP-12, to be both safe and efficacious based on early testing, and a 2-year conditional license for use in U.S. livestock has been issued. The purpose of this study was to further determine the vaccine's potential to infect mosquitoes, the duration of humoral immunity to 24 months postvaccination, and the ability to prevent disease and viremia from a virulent challenge. Vaccination experiments conducted in sheep found no evidence of a potential for vector transmission to 4 North American mosquito species. Neutralizing antibodies were elicited, with titers of >1:40 still present at 24 months postvaccination. Vaccinates were protected from clinical signs and detectable viremia after challenge with virulent virus, while control sheep had fever and high-titered viremia extending for 5 days. Antibodies to three viral proteins (nucleocapsid N, the N-terminal half of glycoprotein GN, and the nonstructural protein from the short segment NSs) were also detected to 24 months using competitive enzyme-linked immunosorbent assays. This study demonstrates that the MP-12 vaccine given as a single dose in sheep generates protective immunity to a virulent challenge with antibody duration of at least 2 years, with no evidence of a risk for vector transmission. PMID:26041042

Ecological distribution and population dynamics of Rift Valley fever virus mosquito vectors (Diptera, Culicidae) in Senegal.

PubMed

Biteye, Biram; Fall, Assane G; Ciss, Mamadou; Seck, Momar T; Apolloni, Andrea; Fall, Moussa; Tran, Annelise; Gimonneau, Geoffrey

2018-01-09

Many zoonotic infectious diseases have emerged and re-emerged over the last two decades. There has been a significant increase in vector-borne diseases due to climate variations that lead to environmental changes favoring the development and adaptation of vectors. This study was carried out to improve knowledge of the ecology of mosquito vectors involved in the transmission of Rift Valley fever virus (RVFV) in Senegal. An entomological survey was conducted in three Senegalese agro-systems, Senegal River Delta (SRD), Senegal River Valley (SRV) and Ferlo, during the rainy season (July to November) of 2014 and 2015. Mosquitoes were trapped using CDC light traps set at ten sites for two consecutive nights during each month of the rainy season, for a total of 200 night-traps. Ecological indices were calculated to characterize the different populations of RVFV mosquito vectors. Generalized linear models with mixed effects were used to assess the influence of climatic conditions on the abundance of RVFV mosquito vectors. A total of 355,408 mosquitoes belonging to 7 genera and 35 species were captured in 200 night-traps. RVFV vectors represented 89.02% of the total, broken down as follows: Ae. vexans arabiensis (31.29%), Cx. poicilipes (0.6%), Cx. tritaeniorhynchus (33.09%) and Ma. uniformis (24.04%). Comparison of meteorological indices (rainfall, temperature, relative humidity), abundances and species diversity indicated that there were no significant differences between SRD and SRV (P = 0.36) while Ferlo showed significant differences with both (P < 0.001). Mosquito collection increased significantly with temperature for Ae. vexans arabiensis (P < 0.001), Cx. tritaeniorhynchus (P = 0.04) and Ma. uniformis (P = 0.01), while Cx. poicilipes decreased (P = 0.003). Relative humidity was positively and significantly associated with the abundances of Ae. vexans arabiensis (P < 0.001), Cx. poicilipes (P = 0.01) and Cx. tritaeniorhynchus (P�

Rift valley Fever virus encephalitis is associated with an ineffective systemic immune response and activated T cell infiltration into the CNS in an immunocompetent mouse model.

PubMed

Dodd, Kimberly A; McElroy, Anita K; Jones, Tara L; Zaki, Sherif R; Nichol, Stuart T; Spiropoulou, Christina F

2014-06-01

Rift Valley fever virus (RVFV) causes outbreaks of severe disease in livestock and humans throughout Africa and the Arabian Peninsula. In people, RVFV generally causes a self-limiting febrile illness but in a subset of individuals, it progresses to more serious disease. One manifestation is a delayed-onset encephalitis that can be fatal or leave the afflicted with long-term neurologic sequelae. In order to design targeted interventions, the basic pathogenesis of RVFV encephalitis must be better understood. To characterize the host immune responses and viral kinetics associated with fatal and nonfatal infections, mice were infected with an attenuated RVFV lacking NSs (ΔNSs) that causes lethal disease only when administered intranasally (IN). Following IN infection, C57BL/6 mice developed severe neurologic disease and succumbed 7-9 days post-infection. In contrast, inoculation of ΔNSs virus subcutaneously in the footpad (FP) resulted in a subclinical infection characterized by a robust immune response with rapid antibody production and strong T cell responses. IN-inoculated mice had delayed antibody responses and failed to clear virus from the periphery. Severe neurological signs and obtundation characterized end stage-disease in IN-inoculated mice, and within the CNS, the development of peak virus RNA loads coincided with strong proinflammatory responses and infiltration of activated T cells. Interestingly, depletion of T cells did not significantly alter survival, suggesting that neurologic disease is not a by-product of an aberrant immune response. Comparison of fatal (IN-inoculated) and nonfatal (FP-inoculated) ΔNSs RVFV infections in the mouse model highlighted the role of the host immune response in controlling viral replication and therefore determining clinical outcome. There was no evidence to suggest that neurologic disease is immune-mediated in RVFV infection. These results provide important insights for the future design of vaccines and therapeutic

Drivers of Rift Valley fever epidemics in Madagascar

PubMed Central

Lancelot, Renaud; Béral, Marina; Rakotoharinome, Vincent Michel; Andriamandimby, Soa-Fy; Héraud, Jean-Michel; Coste, Caroline; Apolloni, Andrea; Squarzoni-Diaw, Cécile; de La Rocque, Stéphane; Wint, G. R. William; Cardinale, Eric

2017-01-01

Rift Valley fever (RVF) is a vector-borne viral disease widespread in Africa. The primary cycle involves mosquitoes and wild and domestic ruminant hosts. Humans are usually contaminated after contact with infected ruminants. As many environmental, agricultural, epidemiological, and anthropogenic factors are implicated in RVF spread, the multidisciplinary One Health approach was needed to identify the drivers of RVF epidemics in Madagascar. We examined the environmental patterns associated with these epidemics, comparing human and ruminant serological data with environmental and cattle-trade data. In contrast to East Africa, environmental drivers did not trigger the epidemics: They only modulated local Rift Valley fever virus (RVFV) transmission in ruminants. Instead, RVFV was introduced through ruminant trade and subsequent movement of cattle between trade hubs caused its long-distance spread within the country. Contact with cattle brought in from infected districts was associated with higher infection risk in slaughterhouse workers. The finding that anthropogenic rather than environmental factors are the main drivers of RVF infection in humans can be used to design better prevention and early detection in the case of RVF resurgence in the region. PMID:28096420

Ecology and Epidemiology of Crimean-Congo Hemorrhagic Fever Virus Transmission in the Republic of Senegal.

DTIC Science & Technology

1992-07-01

that simultaneously circulate in the region were investigated. Most notably, studies of Rift Valley fever ( RVF ) virus transmission in southern Mauritania...and Senegal were undertaken: we documented antibody prevalance in domestic animals during the 1987 outbreak, a decline in RVF virus transmission...following that epidemic, and human risk factors for RVF and associated mosquito vectors in Senegal. - 1 - FOREWORD Citations of commercial organizations

Valley Fever (Coccidioidomycosis) Statistics

MedlinePlus

... Valley fever may be under-recognized. 2 , 3 Public health surveillance for Valley fever Valley fever is reportable ... MMWR) . Check with your local, state, or territorial public health department for more information about disease reporting requirements ...

Rift Valley fever: the Nigerian story.

PubMed

Adeyeye, Adewale A; Ekong, Pius S; Pilau, Nicholas N

2011-01-01

Rift Valley fever (RVF) is an arthropod-borne zoonotic disease of livestock. It is characterised by fever, salivation, abdominal pain, diarrhoea, mucopurulent to bloody nasal discharge, abortion, rapid decrease in milk production and death in animals. Infected humans experience an influenza-like illness that is characterised by fever, malaise, headaches, nausea and epigastric pain followed by recovery, although mortality can occur. RVF was thought to be a disease of sub-Saharan Africa but with the outbreaks in Egypt and the Arabian Peninsula, it may be extending its range further afield. Virological and serological evidence indicates that the virus exists in Nigeria and, with the warning signal sent by international organisations to countries in Africa about an impending outbreak, co-ordinated research between veterinarians and physicians in Nigeria is advocated.

Experimental infection of calves by two genetically-distinct strains of rift valley fever virus

USDA-ARS?s Scientific Manuscript database

Recent outbreaks of Rift Valley fever in ruminant livestock, characterized by mass abortion and high mortality rates in neonates, have raised international interest in improving vaccine control strategies. Previously we developed a reliable challenge model for sheep that improves the evaluation of ...

Application of Droplet Digital PCR to Validate Rift Valley Fever Vaccines.

PubMed

Ly, Hoai J; Lokugamage, Nandadeva; Ikegami, Tetsuro

2016-01-01

Droplet Digital™ polymerase chain reaction (ddPCR™) is a promising technique that quantitates the absolute concentration of nucleic acids in a given sample. This technique utilizes water-in-oil emulsion technology, a system developed by Bio-Rad Laboratories that partitions a single sample into thousands of nanoliter-sized droplets and counts nucleic acid molecules encapsulated in each individual particle as one PCR reaction. This chapter discusses the applications and methodologies of ddPCR for development of Rift Valley fever (RVF) vaccine, using an example that measures RNA copy numbers of a live-attenuated MP-12 vaccine from virus stocks, infected cells, or animal blood. We also discuss how ddPCR detects a reversion mutant of MP-12 from virus stocks accurately. The use of ddPCR improves the quality control of live-attenuated vaccines in the seed lot systems.

Valley polarization in bismuth

NASA Astrophysics Data System (ADS)

Fauque, Benoit

2013-03-01

The electronic structure of certain crystal lattices can contain multiple degenerate valleys for their charge carriers to occupy. The principal challenge in the development of valleytronics is to lift the valley degeneracy of charge carriers in a controlled way. In bulk semi-metallic bismuth, the Fermi surface includes three cigar-shaped electron valleys lying almost perpendicular to the high symmetry axis known as the trigonal axis. The in-plane mass anisotropy of each valley exceeds 200 as a consequence of Dirac dispersion, which drastically reduces the effective mass along two out of the three orientations. According to our recent study of angle-dependent magnetoresistance in bismuth, a flow of Dirac electrons along the trigonal axis is extremely sensitive to the orientation of in-plane magnetic field. Thus, a rotatable magnetic field can be used as a valley valve to tune the contribution of each valley to the total conductivity. As a consequence of a unique combination of high mobility and extreme mass anisotropy in bismuth, the effect is visible even at room temperature in a magnetic field of 1 T. Thus, a modest magnetic field can be used as a valley valve in bismuth. The results of our recent investigation of angle-dependent magnetoresistance in other semi-metals and doped semiconductors suggest that a rotating magnetic field can behave as a valley valve in a multi-valley system with sizeable mass anisotropy.

Novel duck parvovirus identified in Cherry Valley ducks (Anas platyrhynchos domesticus), China.

PubMed

Li, Chuanfeng; Li, Qi; Chen, Zongyan; Liu, Guangqing

2016-10-01

An unknown infectious disease in Cherry Valley ducks (Anas platyrhynchos domesticus) characterized by short beak and strong growth retardation occurred in China during 2015. The causative agent of this disease, tentatively named duck short beak and dwarfism syndrome (DSBDS), as well as the evolutionary relationships between this causative agent and all currently known avian-origin parvoviruses were clarified by virus isolation, transmission electron microscope (TEM) observation, analysis of nuclear acid type, (RT-)PCR identification, whole genome sequencing, and NS1 protein sequences-based phylogenetic analyses. The results indicated that the causative agent of DSBDS is closely related with the goose parvovirus-like virus, which is divergent from all currently known avian-origin parvoviruses and should be a novel duck parvovirus (NDPV). Copyright © 2016 Elsevier B.V. All rights reserved.

Correlative Gene Expression to Protective Seroconversion in Rift Valley Fever Vaccinates.

PubMed

Laughlin, Richard C; Drake, Kenneth L; Morrill, John C; Adams, L Garry

2016-01-01

Rift Valley fever Virus (RVFV), a negative-stranded RNA virus, is the etiological agent of the vector-borne zoonotic disease, Rift Valley fever (RVF). In both humans and livestock, protective immunity can be achieved through vaccination. Earlier and more recent vaccine trials in cattle and sheep demonstrated a strong neutralizing antibody and total IgG response induced by the RVF vaccine, authentic recombinant MP-12 (arMP-12). From previous work, protective immunity in sheep and cattle vaccinates normally occurs from 7 to 21 days after inoculation with arMP-12. While the serology and protective response induced by arMP-12 has been studied, little attention has been paid to the underlying molecular and genetic events occurring prior to the serologic immune response. To address this, we isolated RNA from whole blood of vaccinated calves over a time course of 21 days before and after vaccination with arMP-12. The time course RNAs were sequenced by RNASeq and bioinformatically analyzed. Our results revealed time-dependent activation or repression of numerous gene ontologies and pathways related to the vaccine induced immune response and its regulation. Additional bioinformatic analyses identified a correlative relationship between specific host immune response genes and protective immunity prior to the detection of protective serum neutralizing antibody responses. These results contribute an important proof of concept for identifying molecular and genetic components underlying the immune response to RVF vaccination and protection prior to serologic detection.

Population Genetics of Two Key Mosquito Vectors of Rift Valley Fever Virus Reveals New Insights into the Changing Disease Outbreak Patterns in Kenya

PubMed Central

Tchouassi, David P.; Bastos, Armanda D. S.; Sole, Catherine L.; Diallo, Mawlouth; Lutomiah, Joel; Mutisya, James; Mulwa, Francis; Borgemeister, Christian; Sang, Rosemary; Torto, Baldwyn

2014-01-01

Rift Valley fever (RVF) outbreaks in Kenya have increased in frequency and range to include northeastern Kenya where viruses are increasingly being isolated from known (Aedes mcintoshi) and newly-associated (Ae. ochraceus) vectors. The factors contributing to these changing outbreak patterns are unclear and the population genetic structure of key vectors and/or specific virus-vector associations, in particular, are under-studied. By conducting mitochondrial and nuclear DNA analyses on >220 Kenyan specimens of Ae. mcintoshi and Ae. ochraceus, we uncovered high levels of vector complexity which may partly explain the disease outbreak pattern. Results indicate that Ae. mcintoshi consists of a species complex with one of the member species being unique to the newly-established RVF outbreak-prone northeastern region of Kenya, whereas Ae. ochraceus is a homogeneous population that appears to be undergoing expansion. Characterization of specimens from a RVF-prone site in Senegal, where Ae. ochraceus is a primary vector, revealed direct genetic links between the two Ae. ochraceus populations from both countries. Our data strongly suggest that unlike Ae. mcintoshi, Ae. ochraceus appears to be a relatively recent, single 'introduction' into Kenya. These results, together with increasing isolations from this vector, indicate that Ae. ochraceus will likely be of greater epidemiological importance in future RVF outbreaks in Kenya. Furthermore, the overall vector complexity calls into question the feasibility of mosquito population control approaches reliant on genetic modification. PMID:25474018

Emerging vector-borne diseases in dromedaries in Tunisia: West Nile, bluetongue, epizootic haemorrhagic disease and Rift Valley fever.

PubMed

Hassine, Thameur B; Amdouni, Jihane; Monaco, Federica; Savini, Giovanni; Sghaier, Soufien; Selimen, Imed B; Chandoul, Walid; Hamida, Khaled B; Hammami, Salah

2017-03-31

A total of 118 sera were collected during 2016 from two groups of dromedaries from Kebili and Medenine governorates in the south of Tunisia. The aim of this study was to provide the first serological investigation of four emerging vector-borne diseases in two groups of dromedaries in Tunisia. Sera were tested by ELISA and serum neutralisation test to identify West Nile virus (WNV), bluetongue virus (BTV), epizootic haemorrhagic disease virus (EHDV) and Rift Valley fever virus (RVFV). In the first group, the seroprevalence for BTV was 4.6%, while in the second group, it was 25.8% for WNV and 9.7% for BTV. Only serotype 1 was detected for BTV in the two groups. No evidence for circulation of RVF and EHD viruses was revealed. Results indicated that dromedaries can be infected with BTV and WNV, suggesting that this species might play a significant role in the epizootiology of these viral diseases in Tunisia and neighbouring countries.

Functional Analysis of Rift Valley Fever Virus NSs Encoding a Partial Truncation

PubMed Central

Head, Jennifer A.; Kalveram, Birte; Ikegami, Tetsuro

2012-01-01

Rift Valley fever virus (RVFV), belongs to genus Phlebovirus of the family Bunyaviridae, causes high rates of abortion and fetal malformation in infected ruminants as well as causing neurological disorders, blindness, or lethal hemorrhagic fever in humans. RVFV is classified as a category A priority pathogen and a select agent in the U.S., and currently there are no therapeutics available for RVF patients. NSs protein, a major virulence factor of RVFV, inhibits host transcription including interferon (IFN)-β mRNA synthesis and promotes degradation of dsRNA-dependent protein kinase (PKR). NSs self-associates at the C-terminus 17 aa., while NSs at aa.210–230 binds to Sin3A-associated protein (SAP30) to inhibit the activation of IFN-β promoter. Thus, we hypothesize that NSs function(s) can be abolished by truncation of specific domains, and co-expression of nonfunctional NSs with intact NSs will result in the attenuation of NSs function by dominant-negative effect. Unexpectedly, we found that RVFV NSs truncated at aa. 6–30, 31–55, 56–80, 81–105, 106–130, 131–155, 156–180, 181–205, 206–230, 231–248 or 249–265 lack functions of IFN–β mRNA synthesis inhibition and degradation of PKR. Truncated NSs were less stable in infected cells, while nuclear localization was inhibited in NSs lacking either of aa.81–105, 106–130, 131–155, 156–180, 181–205, 206–230 or 231–248. Furthermore, none of truncated NSs had exhibited significant dominant-negative functions for NSs-mediated IFN-β suppression or PKR degradation upon co-expression in cells infected with RVFV. We also found that any of truncated NSs except for intact NSs does not interact with RVFV NSs even in the presence of intact C-terminus self-association domain. Our results suggest that conformational integrity of NSs is important for the stability, cellular localization and biological functions of RVFV NSs, and the co-expression of truncated NSs does not exhibit dominant

Rift Valley fever virus NSs protein promotes post-transcriptional downregulation of protein kinase PKR and inhibits eIF2alpha phosphorylation.

PubMed

Ikegami, Tetsuro; Narayanan, Krishna; Won, Sungyong; Kamitani, Wataru; Peters, C J; Makino, Shinji

2009-02-01

Rift Valley fever virus (RVFV) (genus Phlebovirus, family Bunyaviridae) is a negative-stranded RNA virus with a tripartite genome. RVFV is transmitted by mosquitoes and causes fever and severe hemorrhagic illness among humans, and fever and high rates of abortions in livestock. A nonstructural RVFV NSs protein inhibits the transcription of host mRNAs, including interferon-beta mRNA, and is a major virulence factor. The present study explored a novel function of the RVFV NSs protein by testing the replication of RVFV lacking the NSs gene in the presence of actinomycin D (ActD) or alpha-amanitin, both of which served as a surrogate of the host mRNA synthesis suppression function of the NSs. In the presence of the host-transcriptional inhibitors, the replication of RVFV lacking the NSs protein, but not that carrying NSs, induced double-stranded RNA-dependent protein kinase (PKR)-mediated eukaryotic initiation factor (eIF)2alpha phosphorylation, leading to the suppression of host and viral protein translation. RVFV NSs promoted post-transcriptional downregulation of PKR early in the course of the infection and suppressed the phosphorylated eIF2alpha accumulation. These data suggested that a combination of RVFV replication and NSs-induced host transcriptional suppression induces PKR-mediated eIF2alpha phosphorylation, while the NSs facilitates efficient viral translation by downregulating PKR and inhibiting PKR-mediated eIF2alpha phosphorylation. Thus, the two distinct functions of the NSs, i.e., the suppression of host transcription, including that of type I interferon mRNAs, and the downregulation of PKR, work together to prevent host innate antiviral functions, allowing efficient replication and survival of RVFV in infected mammalian hosts.

Predicting the mosquito species and vertebrate species involved in the theoretical transmission of Rift Valley fever virus in the United States.

PubMed

Golnar, Andrew J; Turell, Michael J; LaBeaud, A Desiree; Kading, Rebekah C; Hamer, Gabriel L

2014-09-01

Rift Valley fever virus (RVFV) is a mosquito-borne virus in the family Bunyaviridiae that has spread throughout continental Africa to Madagascar and the Arabian Peninsula. The establishment of RVFV in North America would have serious consequences for human and animal health in addition to a significant economic impact on the livestock industry. Published and unpublished data on RVFV vector competence, vertebrate host competence, and mosquito feeding patterns from the United States were combined to quantitatively implicate mosquito vectors and vertebrate hosts that may be important to RVFV transmission in the United States. A viremia-vector competence relationship based on published mosquito transmission studies was used to calculate a vertebrate host competence index which was then combined with mosquito blood feeding patterns to approximate the vector and vertebrate amplification fraction, defined as the relative contribution of the mosquito or vertebrate host to pathogen transmission. Results implicate several Aedes spp. mosquitoes and vertebrates in the order Artiodactyla as important hosts for RVFV transmission in the U.S. Moreover, this study identifies critical gaps in knowledge which would be necessary to complete a comprehensive analysis identifying the different contributions of mosquitoes and vertebrates to potential RVFV transmission in the U.S. Future research should focus on (1) the dose-dependent relationship between viremic exposure and the subsequent infectiousness of key mosquito species, (2) evaluation of vertebrate host competence for RVFV among North American mammal species, with particular emphasis on the order Artiodactyla, and (3) identification of areas with a high risk for RVFV introduction so data on local vector and host populations can help generate geographically appropriate amplification fraction estimates.

Predicting the Mosquito Species and Vertebrate Species Involved in the Theoretical Transmission of Rift Valley Fever Virus in the United States

PubMed Central

Golnar, Andrew J.; Turell, Michael J.; LaBeaud, A. Desiree; Kading, Rebekah C.; Hamer, Gabriel L.

2014-01-01

Rift Valley fever virus (RVFV) is a mosquito-borne virus in the family Bunyaviridiae that has spread throughout continental Africa to Madagascar and the Arabian Peninsula. The establishment of RVFV in North America would have serious consequences for human and animal health in addition to a significant economic impact on the livestock industry. Published and unpublished data on RVFV vector competence, vertebrate host competence, and mosquito feeding patterns from the United States were combined to quantitatively implicate mosquito vectors and vertebrate hosts that may be important to RVFV transmission in the United States. A viremia-vector competence relationship based on published mosquito transmission studies was used to calculate a vertebrate host competence index which was then combined with mosquito blood feeding patterns to approximate the vector and vertebrate amplification fraction, defined as the relative contribution of the mosquito or vertebrate host to pathogen transmission. Results implicate several Aedes spp. mosquitoes and vertebrates in the order Artiodactyla as important hosts for RVFV transmission in the U.S. Moreover, this study identifies critical gaps in knowledge which would be necessary to complete a comprehensive analysis identifying the different contributions of mosquitoes and vertebrates to potential RVFV transmission in the U.S. Future research should focus on (1) the dose-dependent relationship between viremic exposure and the subsequent infectiousness of key mosquito species, (2) evaluation of vertebrate host competence for RVFV among North American mammal species, with particular emphasis on the order Artiodactyla, and (3) identification of areas with a high risk for RVFV introduction so data on local vector and host populations can help generate geographically appropriate amplification fraction estimates. PMID:25211133

Optical manipulation of valley pseudospin

DOE PAGES

Ye, Ziliang; Sun, Dezheng; Heinz, Tony F.

2016-09-19

The coherent manipulation of spin and pseudospin underlies existing and emerging quantum technologies, including quantum communication and quantum computation. Valley polarization, associated with the occupancy of degenerate, but quantum mechanically distinct valleys in momentum space, closely resembles spin polarization and has been proposed as a pseudospin carrier for the future quantum electronics. Valley exciton polarization has been created in the transition metal dichalcogenide monolayers using excitation by circularly polarized light and has been detected both optically and electrically. In addition, the existence of coherence in the valley pseudospin has been identified experimentally. The manipulation of such valley coherence has, however,more » remained out of reach. In this paper, we demonstrate all-optical control of the valley coherence by means of the pseudomagnetic field associated with the optical Stark effect. Using below-bandgap circularly polarized light, we rotate the valley exciton pseudospin in monolayer WSe 2 on the femtosecond timescale. Both the direction and speed of the rotation can be manipulated optically by tuning the dynamic phase of excitons in opposite valleys. Finally, this study unveils the possibility of generation, manipulation, and detection of the valley pseudospin by coupling to photons.« less

NSs Protein of Rift Valley Fever Virus Promotes Posttranslational Downregulation of the TFIIH Subunit p62▿

PubMed Central

Kalveram, Birte; Lihoradova, Olga; Ikegami, Tetsuro

2011-01-01

Rift Valley fever virus (RVFV; family Bunyaviridae, genus Phlebovirus) is an important emerging pathogen of humans and ruminants. Its NSs protein has previously been identified as a major virulence factor that suppresses host defense through three distinct mechanisms: it directly inhibits beta interferon (IFN-β) promoter activity, it promotes the degradation of double-stranded RNA-dependent protein kinase (PKR), and it suppresses host transcription by disrupting the assembly of the basal transcription factor TFIIH through sequestration of its p44 subunit. Here, we report that in addition to PKR, NSs also promotes the degradation of the TFIIH subunit p62. Infection of cells with the RVFV MP-12 vaccine strain reduced p62 protein levels to below the detection limit early in the course of infection. This NSs-mediated downregulation of p62 was posttranslational, as it was unaffected by pharmacological inhibition of transcription or translation and MP-12 infection had no effect on p62 mRNA levels. Treatment of cells with proteasome inhibitors but not inhibition of lysosomal acidification or nuclear export resulted in a stabilization of p62 in the presence of NSs. Furthermore, p62 could be coprecipitated with NSs from lysates of infected cells. These data suggest that the RVFV NSs protein is able to interact with the TFIIH subunit p62 inside infected cells and promotes its degradation, which can occur directly in the nucleus. PMID:21543505

Advances in Rift Valley Fever Research: Insights for Disease Prevention

PubMed Central

LaBeaud, A. Desiree; Kazura, James W.; King, Charles H.

2011-01-01

Purpose of review The purpose of the study was to review recent research on Rift Valley fever virus (RVFV) infection, encompassing four main areas: epidemiology and outbreak prediction, viral pathogenesis, human diagnostics and therapeutics, and vaccine and therapeutic candidates. Recent findings RVFV continues to extend its range in Africa and the Middle East. Better definition of RVFV-related clinical syndromes and human risk factors for severe disease, combined with early-warning systems based on remote-sensing, simplified rapid diagnostics, and tele-epidemiology, hold promise for earlier deployment of effective outbreak control measures. Advances in understanding of viral replication pathways and host cell-related pathogenesis suggest means for antiviral therapeutics and for more effective vaccination strategies based on genetically engineered virus strains or subunit vaccines. Summary RVFV is a significant health and economic burden in many areas of Africa, and remains a serious threat to other parts of the world. Development of more effective methods for RVFV outbreak prevention and control remains a global health priority. PMID:20613512

A Multiplex PCR/LDR Assay for the Simultaneous Identification of Category A Infectious Pathogens: Agents of Viral Hemorrhagic Fever and Variola Virus

PubMed Central

Das, Sanchita; Rundell, Mark S.; Mirza, Aashiq H.; Pingle, Maneesh R.; Shigyo, Kristi; Garrison, Aura R.; Paragas, Jason; Smith, Scott K.; Olson, Victoria A.; Larone, Davise H.; Spitzer, Eric D.; Barany, Francis; Golightly, Linnie M.

2015-01-01

CDC designated category A infectious agents pose a major risk to national security and require special action for public health preparedness. They include viruses that cause viral hemorrhagic fever (VHF) syndrome as well as variola virus, the agent of smallpox. VHF is characterized by hemorrhage and fever with multi-organ failure leading to high morbidity and mortality. Smallpox, a prior scourge, has been eradicated for decades, making it a particularly serious threat if released nefariously in the essentially non-immune world population. Early detection of the causative agents, and the ability to distinguish them from other pathogens, is essential to contain outbreaks, implement proper control measures, and prevent morbidity and mortality. We have developed a multiplex detection assay that uses several species-specific PCR primers to generate amplicons from multiple pathogens; these are then targeted in a ligase detection reaction (LDR). The resultant fluorescently-labeled ligation products are detected on a universal array enabling simultaneous identification of the pathogens. The assay was evaluated on 32 different isolates associated with VHF (ebolavirus, marburgvirus, Crimean Congo hemorrhagic fever virus, Lassa fever virus, Rift Valley fever virus, Dengue virus, and Yellow fever virus) as well as variola virus and vaccinia virus (the agent of smallpox and its vaccine strain, respectively). The assay was able to detect all viruses tested, including 8 sequences representative of different variola virus strains from the CDC repository. It does not cross react with other emerging zoonoses such as monkeypox virus or cowpox virus, or six flaviviruses tested (St. Louis encephalitis virus, Murray Valley encephalitis virus, Powassan virus, Tick-borne encephalitis virus, West Nile virus and Japanese encephalitis virus). PMID:26381398

A Multiplex PCR/LDR Assay for the Simultaneous Identification of Category A Infectious Pathogens: Agents of Viral Hemorrhagic Fever and Variola Virus.

PubMed

Das, Sanchita; Rundell, Mark S; Mirza, Aashiq H; Pingle, Maneesh R; Shigyo, Kristi; Garrison, Aura R; Paragas, Jason; Smith, Scott K; Olson, Victoria A; Larone, Davise H; Spitzer, Eric D; Barany, Francis; Golightly, Linnie M

2015-01-01

CDC designated category A infectious agents pose a major risk to national security and require special action for public health preparedness. They include viruses that cause viral hemorrhagic fever (VHF) syndrome as well as variola virus, the agent of smallpox. VHF is characterized by hemorrhage and fever with multi-organ failure leading to high morbidity and mortality. Smallpox, a prior scourge, has been eradicated for decades, making it a particularly serious threat if released nefariously in the essentially non-immune world population. Early detection of the causative agents, and the ability to distinguish them from other pathogens, is essential to contain outbreaks, implement proper control measures, and prevent morbidity and mortality. We have developed a multiplex detection assay that uses several species-specific PCR primers to generate amplicons from multiple pathogens; these are then targeted in a ligase detection reaction (LDR). The resultant fluorescently-labeled ligation products are detected on a universal array enabling simultaneous identification of the pathogens. The assay was evaluated on 32 different isolates associated with VHF (ebolavirus, marburgvirus, Crimean Congo hemorrhagic fever virus, Lassa fever virus, Rift Valley fever virus, Dengue virus, and Yellow fever virus) as well as variola virus and vaccinia virus (the agent of smallpox and its vaccine strain, respectively). The assay was able to detect all viruses tested, including 8 sequences representative of different variola virus strains from the CDC repository. It does not cross react with other emerging zoonoses such as monkeypox virus or cowpox virus, or six flaviviruses tested (St. Louis encephalitis virus, Murray Valley encephalitis virus, Powassan virus, Tick-borne encephalitis virus, West Nile virus and Japanese encephalitis virus).

Shifting Clade Distribution, Reassortment, and Emergence of New Subtypes of Highly Pathogenic Avian Influenza A(H5) Viruses Collected from Vietnamese Poultry from 2012 to 2015

PubMed Central

Jang, Yunho; Nguyen, Tho D.; Jones, Joyce; Shepard, Samuel S.; Yang, Hua; Gerloff, Nancy; Nguyen, Long V.; Inui, Ken; Yang, Genyan; Creanga, Adrian; Wang, Li; Mai, Duong T.; Thor, Sharmi; Stevens, James; To, Thanh L.; Wentworth, David E.; Nguyen, Tung; Pham, Dong V.; Bryant, Juliet E.

2016-01-01

ABSTRACT Whole-genome sequences of representative highly pathogenic avian influenza A(H5) viruses from Vietnam were generated, comprising samples from poultry outbreaks and active market surveillance collected from January 2012 to August 2015. Six hemagglutinin gene clades were characterized. Clade 1.1.2 was predominant in southern Mekong provinces throughout 2012 and 2013 but gradually disappeared and was not detected after April 2014. Clade 2.3.2.1c viruses spread rapidly during 2012 and were detected in the south and center of the country. A number of clade 1.1.2 and 2.3.2.1c interclade reassortant viruses were detected with different combinations of internal genes derived from 2.3.2.1a and 2.3.2.1b viruses, indicating extensive cocirculation. Although reassortment generated genetic diversity at the genotype level, there was relatively little genetic drift within the individual gene segments, suggesting genetic stasis over recent years. Antigenically, clade 1.1.2, 2.3.2.1a, 2.3.2.1b, and 2.3.2.1c viruses remained related to earlier viruses and WHO-recommended prepandemic vaccine strains representing these clades. Clade 7.2 viruses, although detected in only low numbers, were the exception, as indicated by introduction of a genetically and antigenically diverse strain in 2013. Clade 2.3.4.4 viruses (H5N1 and H5N6) were likely introduced in April 2014 and appeared to gain dominance across northern and central regions. Antigenic analyses of clade 2.3.4.4 viruses compared to existing clade 2.3.4 candidate vaccine viruses (CVV) indicated the need for an updated vaccine virus. A/Sichuan/26221/2014 (H5N6) virus was developed, and ferret antisera generated against this virus were demonstrated to inhibit some but not all clade 2.3.4.4 viruses, suggesting consideration of alternative clade 2.3.4.4 CVVs. IMPORTANCE Highly pathogenic avian influenza (HPAI) A(H5) viruses have circulated continuously in Vietnam since 2003, resulting in hundreds of poultry outbreaks and

Rift Valley Fever Outbreak in Livestock in Kenya, 2006–2007

PubMed Central

Munyua, Peninah; Murithi, Rees M.; Wainwright, Sherrilyn; Githinji, Jane; Hightower, Allen; Mutonga, David; Macharia, Joseph; Ithondeka, Peter M.; Musaa, Joseph; Breiman, Robert F.; Bloland, Peter; Njenga, M. Kariuki

2010-01-01

We analyzed the extent of livestock involvement in the latest Rift Valley fever (RVF) outbreak in Kenya that started in December 2006 and continued until June 2007. When compared with previous RVF outbreaks in the country, the 2006–07 outbreak was the most extensive in cattle, sheep, goats, and camels affecting thousands of animals in 29 of 69 administrative districts across six of the eight provinces. This contrasted with the distribution of approximately 700 human RVF cases in the country, where over 85% of these cases were located in four districts; Garissa and Ijara districts in Northeastern Province, Baringo district in Rift Valley Province, and Kilifi district in Coast Province. Analysis of livestock and human data suggests that livestock infections occur before virus detection in humans, as supported by clustering of human RVF cases around livestock cases in Baringo district. The highest livestock morbidity and mortality rates were recorded in Garissa and Baringo districts, the same districts that recorded a high number of human cases. The districts that reported RVF in livestock for the first time in 2006/07 included Kitui, Tharaka, Meru South, Meru central, Mwingi, Embu, and Mbeere in Eastern Province, Malindi and Taita taveta in Coast Province, Kirinyaga and Murang'a in Central Province, and Baringo and Samburu in Rift Valley Province, indicating that the disease was occurring in new regions in the country. PMID:20682907

Chuckwalla Valley multiple-well monitoring site, Chuckwalla Valley, Riverside County

USGS Publications Warehouse

Everett, Rhett

2013-01-01

The U.S. Geological Survey (USGS), in cooperation with the Bureau of Land Management, is evaluating the geohydrology and water availability of the Chuckwalla Valley, California. As part of this evaluation, the USGS installed the Chuckwalla Valley multiple-well monitoring site (CWV1) in the southeastern portion of the Chuckwalla Basin. Data collected at this site provide information about the geology, hydrology, geophysics, and geochemistry of the local aquifer system, thus enhancing the understanding of the geohydrologic framework of the Chuckwalla Valley. This report presents construction information for the CWV1 multiple-well monitoring site and initial geohydrologic data collected from the site.

The ecology and epidemiology of Ross River and Murray Valley encephalitis viruses in Western Australia: examples of One Health in Action

PubMed Central

Mackenzie, John S; Lindsay, Michael D A; Smith, David W; Imrie, Allison

2017-01-01

Abstract Arboviruses are maintained and transmitted through an alternating biological cycle in arthropods and vertebrates, with largely incidental disease in humans and animals. As such, they provide excellent examples of One Health, as their health impact is inextricably linked to their vertebrate hosts, their arthropod vectors and the environment. Prevention and control requires a comprehensive understanding of these interactions, and how they may be effectively and safely modified. This review concentrates on human disease due to Ross River and Murray Valley encephalitis viruses, the two major arboviral pathogens in Australia. It describes how their pattern of infection and disease is influenced by natural climatic and weather patterns, and by anthropogenic activities. The latter includes human-mediated environmental manipulations, such as water impoundment infrastructures, human movements and migration, and community and social changes, such as urban spread into mosquito larval habitats. Effective interventions need to be directed at the environmental precursors of risk. This can best be achieved using One Health approaches to improve collaboration and coordination between different disciplines and cross-sectoral jurisdictions in order to develop more holistic mitigation and control procedures, and to address poorly understood ecological issues through multidisciplinary research. PMID:29044370

Sacramento Valley, CA, USA

NASA Technical Reports Server (NTRS)

1973-01-01

The Sacramento Valley (40.5N, 121.5W) of California is the northern extension of the Central Valley, main agriculture region of the state. Hundreds of truck farms, vineyards and orchards can be seen throughout the length and breadth of the valley which was reclaimed from the desert by means of intensive and extensive irrigation projects.

Recombinant Rift Valley fever vaccines induce protective levels of antibody in baboons and resistance to lethal challenge in mice

PubMed Central

Papin, James F.; Verardi, Paulo H.; Jones, Leslie A.; Monge-Navarro, Francisco; Brault, Aaron C.; Holbrook, Michael R.; Worthy, Melissa N.; Freiberg, Alexander N.; Yilma, Tilahun D.

2011-01-01

Rift Valley fever (RVF) is a zoonotic disease endemic in Africa and the Arabian Peninsula caused by the highly infectious Rift Valley fever virus (RVFV) that can be lethal to humans and animals and results in major losses in the livestock industry. RVF is exotic to the United States; however, mosquito species native to this region can serve as biological vectors for the virus. Thus, accidental or malicious introduction of this virus could result in RVFV becoming endemic in North America. Such an event would likely lead to significant morbidity and mortality in humans, and devastating economic effects on the livestock industry. Currently, there are no licensed vaccines for RVF that are both safe and efficacious. To address this issue, we developed two recombinant RVFV vaccines using vaccinia virus (VACV) as a vector for use in livestock. The first vaccine, vCOGnGc, was attenuated by the deletion of a VACV gene encoding an IFN-γ binding protein, insertional inactivation of the thymidine kinase gene, and expression of RVFV glycoproteins, Gn and Gc. The second vaccine, vCOGnGcγ, is identical to the first and also expresses the human IFN-γ gene to enhance safety. Both vaccines are extremely safe; neither resulted in weight loss nor death in severe combined immunodeficient mice, and pock lesions were smaller in baboons compared with the controls. Furthermore, both vaccines induced protective levels of antibody titers in vaccinated mice and baboons. Mice were protected from lethal RVFV challenge. Thus, we have developed two safe and efficacious recombinant vaccines for RVF. PMID:21873194

Mutation of adjacent cysteine residues in the NSs protein of Rift Valley fever virus results in loss of virulence in mice.

PubMed

Monteiro, Gaby E R; Jansen van Vuren, Petrus; Wichgers Schreur, Paul J; Odendaal, Lieza; Clift, Sarah J; Kortekaas, Jeroen; Paweska, Janusz T

2018-04-02

The NSs protein encoded by the S segment of Rift Valley fever virus (RVFV) is the major virulence factor, counteracting the host innate antiviral defence. It contains five highly conserved cysteine residues at positions 39, 40, 149, 178 and 194, which are thought to stabilize the tertiary and quaternary structure of the protein. Here, we report significant differences between clinical, virological, histopathological and host gene responses in BALB/c mice infected with wild-type RVFV (wtRVFV) or a genetic mutant having a double cysteine-to-serine substitution at residues 39 and 40 of the NSs protein (RVFV-C39S/C40S). Mice infected with the wtRVFV developed a fatal acute disease; characterized by high levels of viral replication, severe hepatocellular necrosis, and massive up-regulation of transcription of genes encoding type I and -II interferons (IFN) as well as pro-apoptotic and pro-inflammatory cytokines. The RVFV-C39S/C40S mutant did not cause clinical disease and its attenuated virulence was consistent with virological, histopathological and host gene expression findings in BALB/c mice. Clinical signs in mice infected with viruses containing cysteine-to-serine substitutions at positions 178 or 194 were similar to those occurring in mice infected with the wtRVFV, while a mutant containing a substitution at position 149 caused mild, non-fatal disease in mice. As mutant RVFV-C39S/C40S showed an attenuated phenotype in mice, the molecular mechanisms behind this attenuation were further investigated. The results show that two mechanisms are responsible for the attenuation; (1) loss of the IFN antagonistic propriety characteristic of the wtRVFV NSs and (2) the inability of the attenuated mutant to degrade Proteine Kinase R (PKR). Copyright © 2018. Published by Elsevier B.V.

Sacramento Valley, CA, USA

NASA Image and Video Library

1973-06-22

SL2-04-179 (22 June 1973) --- The Sacramento Valley (40.5N, 121.5W) of California is the northern extension of the Central Valley, main agriculture region of the state. Hundreds of truck farms, vineyards and orchards can be seen throughout the length and breadth of the valley which was reclaimed from the desert by means of intensive and extensive irrigation projects. Photo credit: NASA

Observation of acoustic valley vortex states and valley-chirality locked beam splitting

NASA Astrophysics Data System (ADS)

Ye, Liping; Qiu, Chunyin; Lu, Jiuyang; Wen, Xinhua; Shen, Yuanyuan; Ke, Manzhu; Zhang, Fan; Liu, Zhengyou

2017-05-01

We report an experimental observation of the classical version of valley polarized states in a two-dimensional hexagonal sonic crystal. The acoustic valley states, which carry specific linear momenta and orbital angular momenta, were selectively excited by external Gaussian beams and conveniently confirmed by the pressure distribution outside the crystal, according to the criterion of momentum conservation. The vortex nature of such intriguing bulk crystal states was directly characterized by scanning the phase profile inside the crystal. In addition, we observed a peculiar beam-splitting phenomenon, in which the separated beams are constructed by different valleys and locked to the opposite vortex chirality. The exceptional sound transport, encoded with valley-chirality locked information, may serve as the basis of designing conceptually interesting acoustic devices with unconventional functions.

Computational prediction and biochemical characterization of novel RNA aptamers to Rift Valley fever virus nucleocapsid protein.

PubMed

Ellenbecker, Mary; St Goddard, Jeremy; Sundet, Alec; Lanchy, Jean-Marc; Raiford, Douglas; Lodmell, J Stephen

2015-10-01

Rift Valley fever virus (RVFV) is a potent human and livestock pathogen endemic to sub-Saharan Africa and the Arabian Peninsula that has potential to spread to other parts of the world. Although there is no proven effective and safe treatment for RVFV infections, a potential therapeutic target is the virally encoded nucleocapsid protein (N). During the course of infection, N binds to viral RNA, and perturbation of this interaction can inhibit viral replication. To gain insight into how N recognizes viral RNA specifically, we designed an algorithm that uses a distance matrix and multidimensional scaling to compare the predicted secondary structures of known N-binding RNAs, or aptamers, that were isolated and characterized in previous in vitro evolution experiment. These aptamers did not exhibit overt sequence or predicted structure similarity, so we employed bioinformatic methods to propose novel aptamers based on analysis and clustering of secondary structures. We screened and scored the predicted secondary structures of novel randomly generated RNA sequences in silico and selected several of these putative N-binding RNAs whose secondary structures were similar to those of known N-binding RNAs. We found that overall the in silico generated RNA sequences bound well to N in vitro. Furthermore, introduction of these RNAs into cells prior to infection with RVFV inhibited viral replication in cell culture. This proof of concept study demonstrates how the predictive power of bioinformatics and the empirical power of biochemistry can be jointly harnessed to discover, synthesize, and test new RNA sequences that bind tightly to RVFV N protein. The approach would be easily generalizable to other applications. Copyright © 2015 Elsevier Ltd. All rights reserved.

Modelling the effects of seasonality and socioeconomic impact on the transmission of Rift Valley fever virus

USGS Publications Warehouse

Xiao, Yanyu; Beier, John C.; Cantrell, Robert Stephen; Cosner, Chris; DeAngelis, Donald L.; Ruan, Shigui

2015-01-01

Rift Valley fever (RVF) is an important mosquito-borne viral zoonosis in Africa and the Middle East that causes human deaths and significant economic losses due to huge incidences of death and abortion among infected livestock. Outbreaks of RVF are sporadic and associated with both seasonal and socioeconomic effects. Here we propose an almost periodic three-patch model to investigate the transmission dynamics of RVF virus (RVFV) among ruminants with spatial movements. Our findings indicate that, in Northeastern Africa, human activities, including those associated with the Eid al Adha feast, along with a combination of climatic factors such as rainfall level and hydrological variations, contribute to the transmission and dispersal of the disease pathogen. Moreover, sporadic outbreaks may occur when the two events occur together: 1) abundant livestock are recruited into areas at risk from RVF due to the demand for the religious festival and 2) abundant numbers of mosquitoes emerge. These two factors have been shown to have impacts on the severity of RVF outbreaks. Our numerical results present the transmission dynamics of the disease pathogen over both short and long periods of time, particularly during the festival time. Further, we investigate the impact on patterns of disease outbreaks in each patch brought by festival- and seasonal-driven factors, such as the number of livestock imported daily, the animal transportation speed from patch to patch, and the death rate induced by ceremonial sacrifices. In addition, our simulations show that when the time for festival preparation starts earlier than usual, the risk of massive disease outbreaks rises, particularly in patch 3 (the place where the religious ceremony will be held).

Dry Valleys, Antarctica

NASA Image and Video Library

2009-11-02

The McMurdo Dry Valleys are a row of valleys west of McMurdo Sound, Antarctica. They are so named because of their extremely low humidity and lack of snow and ice cover. This image was acquired December 8, 2002 by NASA Terra spacecraft.

Seroepidemiological Study of Interepidemic Rift Valley Fever Virus Infection Among Persons with Intense Ruminant Exposure in Madagascar and Kenya.

PubMed

Gray, Gregory C; Anderson, Benjamin D; LaBeaud, A Desirée; Heraud, Jean-Michel; Fèvre, Eric M; Andriamandimby, Soa Fy; Cook, Elizabeth A J; Dahir, Saidi; de Glanville, William A; Heil, Gary L; Khan, Salah U; Muiruri, Samuel; Olive, Marie-Marie; Thomas, Lian F; Merrill, Hunter R; Merrill, Mary L M; Richt, Juergen A

2015-12-01

In this cross-sectional seroepidemiological study we sought to examine the evidence for circulation of Rift Valley fever virus (RVFV) among herders in Madagascar and Kenya. From July 2010 to June 2012, we enrolled 459 herders and 98 controls (without ruminant exposures) and studied their sera (immunoglobulin G [IgG] and IgM through enzyme-linked immunosorbent assay [ELISA] and plaque reduction neutralization test [PRNT] assays) for evidence of previous RVFV infection. Overall, 59 (12.9%) of 459 herders and 7 (7.1%) of the 98 controls were positive by the IgG ELISA assay. Of the 59 ELISA-positive herders, 23 (38.9%) were confirmed by the PRNT assay (21 from eastern Kenya). Two of the 21 PRNT-positive study subjects also had elevated IgM antibodies against RVFV suggesting recent infection. Multivariate modeling in this study revealed that being seminomadic (odds ratio [OR] = 6.4, 95% confidence interval [CI] = 2.1-15.4) was most strongly associated with antibodies against RVFV. Although we cannot know when these infections occurred, it seems likely that some interepidemic RVFV infections are occurring among herders. As there are disincentives regarding reporting RVFV outbreaks in livestock or wildlife, it may be prudent to conduct periodic, limited, active seroepidemiological surveillance for RVFV infections in herders, especially in eastern Kenya. © The American Society of Tropical Medicine and Hygiene.

Severe Human Illness Caused by Rift Valley Fever Virus in Mauritania, 2015.

PubMed

Boushab, Boushab Mohamed; Fall-Malick, Fatima Zahra; Ould Baba, Sidi El Wafi; Ould Salem, Mohamed Lemine; Belizaire, Marie Roseline Darnycka; Ledib, Hamade; Ould Baba Ahmed, Mohamed Mahmoud; Basco, Leonardo Kishi; Ba, Hampaté

2016-10-01

Rift Valley Fever epizootics are characterized by numerous abortions and mortality among young animals. In humans, the illness is usually characterized by a mild self-limited febrile illness, which could progress to more serious complications.Objectives. The aim of the present prospective study was to describe severe clinical signs and symptoms of Rift Valley Fever in southern Mauritania. Suspected cases were enrolled in Kiffa (Assaba) and Aleg (Brakna) Hospital Centers from September 1 to November 7, 2015, based on the presence of fever, hemorrhagic or meningoencephalitic syndromes, and probable contact with sick animals. Suspected cases were confirmed by enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase-polymerase chain reaction (RT-PCR). There were thirty-one confirmed cases. The sex ratio M/F and the average age were 2.9 and 25 years old [range, 4-70 years old], respectively. Mosquito bites, direct contact with aborted or dead animals, and frequent ingestion of milk from these animals were risk factors observed in all patients. Hemorrhagic and neurological manifestations were observed in 81% and 13% of cases, respectively. The results of laboratory analysis showed high levels of transaminases, creatinine, and urea associated with thrombocytopenia, anemia, and leukopenia. All patients who died (42%) had a hemorrhagic syndrome and 3 of them had a neurological complication. Among the cured patients, none had neurologic sequelae. The hemorrhagic form was the most common clinical manifestation of RVF found in southern Mauritania and was responsible for a high mortality rate. Our results justify the implementation of a continuous epidemiological surveillance.

Ground-water conditions in southern Utah Valley and Goshen Valley, Utah

USGS Publications Warehouse

Cordova, R.M.

1970-01-01

The investigation of ground-water conditions in southern Utah Valley and Goshen Valley, Utah, was made by the U. S. Geological Survey as part of a cooperative program with the Utah Department of Natural Resources, Division of Water Rights, to investigate the water resources of the State. The purposes of the investigation were to (1) determine the occurrence, recharge, discharge, movement, storage, chemical quality, and availability of ground water; (2) appraise the effects of increased withdrawal of water from wells; and (3) evaluate the effect of the Central Utah Project on the ground-water reservoir and the water supply of Utah Lake.This report presents a description of the aquifer system in the two valleys, a detailed description of the ground-water resources, and conclusions about potential development and its effect on the hydrologic conditions in the valleys. Two supplementary reports are products of the investigation. A basic-data release (Cordova, 1969) contains most of the basic data collected for the investigation, including well characteristics, drillers' logs, water levels, pumpage from wells, chemical analyses of ground and surface waters, and discharge of selected springs, drains, and streams. An interpretive report (Cordova and Mower, 1967) contains the results of a large-scale aquifer test in southern Utah Valley.

The Consequences of Reconfiguring the Ambisense S Genome Segment of Rift Valley Fever Virus on Viral Replication in Mammalian and Mosquito Cells and for Genome Packaging

PubMed Central

Elliott, Richard M.

2014-01-01

Rift Valley fever virus (RVFV, family Bunyaviridae) is a mosquito-borne pathogen of both livestock and humans, found primarily in Sub-Saharan Africa and the Arabian Peninsula. The viral genome comprises two negative-sense (L and M segments) and one ambisense (S segment) RNAs that encode seven proteins. The S segment encodes the nucleocapsid (N) protein in the negative-sense and a nonstructural (NSs) protein in the positive-sense, though NSs cannot be translated directly from the S segment but rather from a specific subgenomic mRNA. Using reverse genetics we generated a virus, designated rMP12:S-Swap, in which the N protein is expressed from the NSs locus and NSs from the N locus within the genomic S RNA. In cells infected with rMP12:S-Swap NSs is expressed at higher levels with respect to N than in cells infected with the parental rMP12 virus. Despite NSs being the main interferon antagonist and determinant of virulence, growth of rMP12:S-Swap was attenuated in mammalian cells and gave a small plaque phenotype. The increased abundance of the NSs protein did not lead to faster inhibition of host cell protein synthesis or host cell transcription in infected mammalian cells. In cultured mosquito cells, however, infection with rMP12:S-Swap resulted in cell death rather than establishment of persistence as seen with rMP12. Finally, altering the composition of the S segment led to a differential packaging ratio of genomic to antigenomic RNA into rMP12:S-Swap virions. Our results highlight the plasticity of the RVFV genome and provide a useful experimental tool to investigate further the packaging mechanism of the segmented genome. PMID:24550727

Analysis of Mining-induced Valley Closure Movements

NASA Astrophysics Data System (ADS)

Zhang, C.; Mitra, R.; Oh, J.; Hebblewhite, B.

2016-05-01

Valley closure movements have been observed for decades in Australia and overseas when underground mining occurred beneath or in close proximity to valleys and other forms of irregular topographies. Valley closure is defined as the inward movements of the valley sides towards the valley centreline. Due to the complexity of the local geology and the interplay between several geological, topographical and mining factors, the underlying mechanisms that actually cause this behaviour are not completely understood. A comprehensive programme of numerical modelling investigations has been carried out to further evaluate and quantify the influence of a number of these mining and geological factors and their inter-relationships. The factors investigated in this paper include longwall positional factors, horizontal stress, panel width, depth of cover and geological structures around the valley. It is found that mining in a series passing beneath the valley dramatically increases valley closure, and mining parallel to valley induces much more closure than other mining orientations. The redistribution of horizontal stress and influence of mining activity have also been recognised as important factors promoting valley closure, and the effect of geological structure around the valley is found to be relatively small. This paper provides further insight into both the valley closure mechanisms and how these mechanisms should be considered in valley closure prediction models.

The Inter-Valley Soil Comparative Survey: the ecology of Dry Valley edaphic microbial communities

PubMed Central

Lee, Charles K; Barbier, Béatrice A; Bottos, Eric M; McDonald, Ian R; Cary, Stephen Craig

2012-01-01

Recent applications of molecular genetics to edaphic microbial communities of the McMurdo Dry Valleys and elsewhere have rejected a long-held belief that Antarctic soils contain extremely limited microbial diversity. The Inter-Valley Soil Comparative Survey aims to elucidate the factors shaping these unique microbial communities and their biogeography by integrating molecular genetic approaches with biogeochemical analyses. Although the microbial communities of Dry Valley soils may be complex, there is little doubt that the ecosystem's food web is relatively simple, and evidence suggests that physicochemical conditions may have the dominant role in shaping microbial communities. To examine this hypothesis, bacterial communities from representative soil samples collected in four geographically disparate Dry Valleys were analyzed using molecular genetic tools, including pyrosequencing of 16S rRNA gene PCR amplicons. Results show that the four communities are structurally and phylogenetically distinct, and possess significantly different levels of diversity. Strikingly, only 2 of 214 phylotypes were found in all four valleys, challenging a widespread assumption that the microbiota of the Dry Valleys is composed of a few cosmopolitan species. Analysis of soil geochemical properties indicated that salt content, alongside altitude and Cu2+, was significantly correlated with differences in microbial communities. Our results indicate that the microbial ecology of Dry Valley soils is highly localized and that physicochemical factors potentially have major roles in shaping the microbiology of ice-free areas of Antarctica. These findings hint at links between Dry Valley glacial geomorphology and microbial ecology, and raise previously unrecognized issues related to environmental management of this unique ecosystem. PMID:22170424

27 CFR 9.132 - Rogue Valley.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Rogue Valley. 9.132... Rogue Valley. (a) Name. The name of the viticultural area described in this section is “Rouge Valley.” (b) Approved map. The appropriate map for determining the boundaries of the Rogue Valley viticultural...

Potential for Mosquitoes (Diptera: Culicidae) From Florida to Transmit Rift Valley Fever Virus

DTIC Science & Technology

2013-09-01

Guide for the Care and Use of Laboratory Animals, NationalResearchCouncil, 2011. Theuse of any speciÞcproduct does not constitute endorsement of that...from North America are competent vectors and might be involved in the natural transmission cycle so that the appropriate control measures can be used if...collected in sufÞ- cient numbers for evaluation (Table 1). Viruses and Virus Assay.We used the ZH501 strain of RVFV, isolated in 1977 from the blood of a 10

Experimental reproduction of beak atrophy and dwarfism syndrome by infection in cherry valley ducklings with a novel goose parvovirus-related parvovirus.

PubMed

Chen, Hao; Dou, Yanguo; Tang, Yi; Zheng, Xiaoqiang; Niu, Xiaoyu; Yang, Jing; Yu, Xianglong; Diao, Youxiang

2016-02-01

Infection of clinically susceptible ducks, including cherry valley and Muscovy ducks, with a novel goose parvovirus (GPV)-related virus (N-GPV) can result in beak atrophy and dwarfism syndrome (BADS). To obtain new insights into the host range and pathogenic potential of this novel waterfowl parvovirus, cherry valley ducklings (n=20) were experimentally infected with N-GPV strain SDLC01. An equal number of ducklings served as uninfected controls. The appearance of clinical signs, histopathological changes, viral shedding, and seroconversion was monitored for 20 days post-infection. Infection status of all ducks was monitored using indirect ELISA, virus neutralization test, nested PCR, clinical indicators, and microscopic examination. Three ducks developed the typical clinical, gross, and histological changes of BADS. By study day 6, the infected ducks had seroconverted to N-GPV. The antibodies raised were neutralizing against the SDLC01 strain in vitro. Here we successfully developed an experimental infection model for studying the pathogenicity and role of N-GPV in BADS. Copyright © 2015 Elsevier B.V. All rights reserved.

Potential for stable flies and house flies (Diptera: Muscidae) to transmit Rift Valley fever virus

USDA-ARS?s Scientific Manuscript database

Rift Valley fever (RVF), a disease of ruminants and humans, has been responsible for large outbreaks in Africa that have resulted in hundreds of thousands of human infections and major economic disruption due to loss of livestock and to trade restrictions. As indicated by the rapid spread of West N...

Incidence of viruses in fescue (Festuca sp.) seed production fields in the Willamette Valley in 2016

USDA-ARS?s Scientific Manuscript database

Tall Fescue seed production fields of Western Oregon were sampled and tested for the presence or absence of three viruses, Barley yellow dwarf virus (BYDV) -MAV and -PAV, and Cereal yellow dwarf virus (CYDV). There was no BYDV-MAV detected in any of the Fescue seed fields. The BYDV-PAV occurred in ...

Development of a sheep challenge model for Rift Valley fever.

PubMed

Faburay, Bonto; Gaudreault, Natasha N; Liu, Qinfang; Davis, A Sally; Shivanna, Vinay; Sunwoo, Sun Young; Lang, Yuekun; Morozov, Igor; Ruder, Mark; Drolet, Barbara; Scott McVey, D; Ma, Wenjun; Wilson, William; Richt, Juergen A

2016-02-01

Rift Valley fever (RVF) is a zoonotic disease that causes severe epizootics in ruminants, characterized by mass abortion and high mortality rates in younger animals. The development of a reliable challenge model is an important prerequisite for evaluation of existing and novel vaccines. A study aimed at comparing the pathogenesis of RVF virus infection in US sheep using two genetically different wild type strains of the virus (SA01-1322 and Kenya-128B-15) was performed. A group of sheep was inoculated with both strains and all infected sheep manifested early-onset viremia accompanied by a transient increase in temperatures. The Kenya-128B-15 strain manifested higher virulence compared to SA01-1322 by inducing more severe liver damage, and longer and higher viremia. Genome sequence analysis revealed sequence variations between the two isolates, which potentially could account for the observed phenotypic differences. We conclude that Kenya-128B-15 sheep infection represents a good and virulent challenge model for RVF. Copyright © 2015 Elsevier Inc. All rights reserved.

Hydrogeologic framework and estimates of groundwater storage for the Hualapai Valley, Detrital Valley, and Sacramento Valley basins, Mohave County, Arizona

USGS Publications Warehouse

Truini, Margot; Beard, L. Sue; Kennedy, Jeffrey; Anning, Dave W.

2013-01-01

We have investigated the hydrogeology of the Hualapai Valley, Detrital Valley, and Sacramento Valley basins of Mohave County in northwestern Arizona to develop a better understanding of groundwater storage within the basin fill aquifers. In our investigation we used geologic maps, well-log data, and geophysical surveys to delineate the sedimentary textures and lithology of the basin fill. We used gravity data to construct a basin geometry model that defines smaller subbasins within the larger basins, and airborne transient-electromagnetic modeled results along with well-log lithology data to infer the subsurface distribution of basin fill within the subbasins. Hydrogeologic units (HGUs) are delineated within the subbasins on the basis of the inferred lithology of saturated basin fill. We used the extent and size of HGUs to estimate groundwater storage to depths of 400 meters (m) below land surface (bls). The basin geometry model for the Hualapai Valley basin consists of three subbasins: the Kingman, Hualapai, and southern Gregg subbasins. In the Kingman subbasin, which is estimated to be 1,200 m deep, saturated basin fill consists of a mixture of fine- to coarse-grained sedimentary deposits. The Hualapai subbasin, which is the largest of the subbasins, contains a thick halite body from about 400 m to about 4,300 m bls. Saturated basin fill overlying the salt body consists predominately of fine-grained older playa deposits. In the southern Gregg subbasin, which is estimated to be 1,400 m deep, saturated basin fill is interpreted to consist primarily of fine- to coarse-grained sedimentary deposits. Groundwater storage to 400 m bls in the Hualapai Valley basin is estimated to be 14.1 cubic kilometers (km3). The basin geometry model for the Detrital Valley basin consists of three subbasins: northern Detrital, central Detrital, and southern Detrital subbasins. The northern and central Detrital subbasins are characterized by a predominance of playa evaporite and fine

The ecology and epidemiology of Ross River and Murray Valley encephalitis viruses in Western Australia: examples of One Health in Action.

PubMed

Mackenzie, John S; Lindsay, Michael D A; Smith, David W; Imrie, Allison

2017-06-01

Arboviruses are maintained and transmitted through an alternating biological cycle in arthropods and vertebrates, with largely incidental disease in humans and animals. As such, they provide excellent examples of One Health, as their health impact is inextricably linked to their vertebrate hosts, their arthropod vectors and the environment. Prevention and control requires a comprehensive understanding of these interactions, and how they may be effectively and safely modified. This review concentrates on human disease due to Ross River and Murray Valley encephalitis viruses, the two major arboviral pathogens in Australia. It describes how their pattern of infection and disease is influenced by natural climatic and weather patterns, and by anthropogenic activities. The latter includes human-mediated environmental manipulations, such as water impoundment infrastructures, human movements and migration, and community and social changes, such as urban spread into mosquito larval habitats. Effective interventions need to be directed at the environmental precursors of risk. This can best be achieved using One Health approaches to improve collaboration and coordination between different disciplines and cross-sectoral jurisdictions in order to develop more holistic mitigation and control procedures, and to address poorly understood ecological issues through multidisciplinary research. © The Author 2017. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.

Common Host-Derived Chemicals Increase Catches of Disease-Transmitting Mosquitoes and Can Improve Early Warning Systems for Rift Valley Fever Virus

PubMed Central

Tchouassi, David P.; Sang, Rosemary; Sole, Catherine L.; Bastos, Armanda D. S.; Teal, Peter E. A.; Borgemeister, Christian; Torto, Baldwyn

2013-01-01

Rift Valley fever (RVF), a mosquito-borne zoonosis, is a major public health and veterinary problem in sub-Saharan Africa. Surveillance to monitor mosquito populations during the inter-epidemic period (IEP) and viral activity in these vectors is critical to informing public health decisions for early warning and control of the disease. Using a combination of field bioassays, electrophysiological and chemical analyses we demonstrated that skin-derived aldehydes (heptanal, octanal, nonanal, decanal) common to RVF virus (RVFV) hosts including sheep, cow, donkey, goat and human serve as potent attractants for RVFV mosquito vectors. Furthermore, a blend formulated from the four aldehydes and combined with CO2-baited CDC trap without a light bulb doubled to tripled trap captures compared to control traps baited with CO2 alone. Our results reveal that (a) because of the commonality of the host chemical signature required for attraction, the host-vector interaction appears to favor the mosquito vector allowing it to find and opportunistically feed on a wide range of mammalian hosts of the disease, and (b) the sensitivity, specificity and superiority of this trapping system offers the potential for its wider use in surveillance programs for RVFV mosquito vectors especially during the IEP. PMID:23326620

Landscape genetics of raccoons (Procyon lotor) associated with ridges and valleys of Pennsylvania: implications for oral rabies vaccination programs.

PubMed

Root, J Jeffrey; Puskas, Robert B; Fischer, Justin W; Swope, Craig B; Neubaum, Melissa A; Reeder, Serena A; Piaggio, Antoinette J

2009-12-01

Raccoons are the reservoir for the raccoon rabies virus variant in the United States. To combat this threat, oral rabies vaccination (ORV) programs are conducted in many eastern states. To aid in these efforts, the genetic structure of raccoons (Procyon lotor) was assessed in southwestern Pennsylvania to determine if select geographic features (i.e., ridges and valleys) serve as corridors or hindrances to raccoon gene flow (e.g., movement) and, therefore, rabies virus trafficking in this physiographic region. Raccoon DNA samples (n = 185) were collected from one ridge site and two adjacent valleys in southwestern Pennsylvania (Westmoreland, Cambria, Fayette, and Somerset counties). Raccoon genetic structure within and among these study sites was characterized at nine microsatellite loci. Results indicated that there was little population subdivision among any sites sampled. Furthermore, analyses using a model-based clustering approach indicated one essentially panmictic population was present among all the raccoons sampled over a reasonably broad geographic area (e.g., sites up to 36 km apart). However, a signature of isolation by distance was detected, suggesting that widths of ORV zones are critical for success. Combined, these data indicate that geographic features within this landscape influence raccoon gene flow only to a limited extent, suggesting that ridges of this physiographic system will not provide substantial long-term natural barriers to rabies virus trafficking. These results may be of value for future ORV efforts in Pennsylvania and other eastern states with similar landscapes.

Fretted Terrain Valleys

NASA Technical Reports Server (NTRS)

2004-01-01

30 October 2004 This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows shallow tributary valleys in the Ismenius Lacus fretted terrain region of northern Arabia Terra. These valleys exhibit a variety of typical fretted terrain valley wall and floor textures, including a lineated, pitted material somewhat reminiscent of the surface of a brain. Origins for these features are still being debated within the Mars science community; there are no clear analogs to these landforms on Earth. This image is located near 39.9oN, 332.1oW. The picture covers an area about 3 km (1.9 mi) wide. Sunlight illuminates the scene from the lower left.

Shifting Clade Distribution, Reassortment, and Emergence of New Subtypes of Highly Pathogenic Avian Influenza A(H5) Viruses Collected from Vietnamese Poultry from 2012 to 2015.

PubMed

Nguyen, Diep T; Jang, Yunho; Nguyen, Tho D; Jones, Joyce; Shepard, Samuel S; Yang, Hua; Gerloff, Nancy; Fabrizio, Thomas; Nguyen, Long V; Inui, Ken; Yang, Genyan; Creanga, Adrian; Wang, Li; Mai, Duong T; Thor, Sharmi; Stevens, James; To, Thanh L; Wentworth, David E; Nguyen, Tung; Pham, Dong V; Bryant, Juliet E; Davis, C Todd

2017-03-01

Whole-genome sequences of representative highly pathogenic avian influenza A(H5) viruses from Vietnam were generated, comprising samples from poultry outbreaks and active market surveillance collected from January 2012 to August 2015. Six hemagglutinin gene clades were characterized. Clade 1.1.2 was predominant in southern Mekong provinces throughout 2012 and 2013 but gradually disappeared and was not detected after April 2014. Clade 2.3.2.1c viruses spread rapidly during 2012 and were detected in the south and center of the country. A number of clade 1.1.2 and 2.3.2.1c interclade reassortant viruses were detected with different combinations of internal genes derived from 2.3.2.1a and 2.3.2.1b viruses, indicating extensive cocirculation. Although reassortment generated genetic diversity at the genotype level, there was relatively little genetic drift within the individual gene segments, suggesting genetic stasis over recent years. Antigenically, clade 1.1.2, 2.3.2.1a, 2.3.2.1b, and 2.3.2.1c viruses remained related to earlier viruses and WHO-recommended prepandemic vaccine strains representing these clades. Clade 7.2 viruses, although detected in only low numbers, were the exception, as indicated by introduction of a genetically and antigenically diverse strain in 2013. Clade 2.3.4.4 viruses (H5N1 and H5N6) were likely introduced in April 2014 and appeared to gain dominance across northern and central regions. Antigenic analyses of clade 2.3.4.4 viruses compared to existing clade 2.3.4 candidate vaccine viruses (CVV) indicated the need for an updated vaccine virus. A/Sichuan/26221/2014 (H5N6) virus was developed, and ferret antisera generated against this virus were demonstrated to inhibit some but not all clade 2.3.4.4 viruses, suggesting consideration of alternative clade 2.3.4.4 CVVs. IMPORTANCE Highly pathogenic avian influenza (HPAI) A(H5) viruses have circulated continuously in Vietnam since 2003, resulting in hundreds of poultry outbreaks and sporadic human

Evidence for Circulation of the Rift Valley Fever Virus among Livestock in the Union of Comoros

PubMed Central

Soulé, Miradje; Faharoudine, Abdourahime; Foray, Coralie; Olive, Marie-Marie; Maquart, Marianne; Soulaimane, Abdouroihamane; Madi Kassim, Ahmed; Cêtre-Sossah, Catherine; Cardinale, Eric

2014-01-01

Rift Valley fever virus (RVFV) is an arthropod-borne phlebovirus reported to be circulating in most parts of Africa. Since 2009, RVFV has been suspected of continuously circulating in the Union of Comoros. To estimate the incidence of RVFV antibody acquisition in the Comorian ruminant population, 191 young goats and cattle were selected in six distinct zones and sampled periodically from April 2010 to August 2011. We found an estimated incidence of RVFV antibody acquisition of 17.5% (95% confidence interval (CI): [8.9–26.1]) with a significant difference between islands (8.2% in Grande Comore, 72.3% in Moheli and 5.8% in Anjouan). Simultaneously, a longitudinal entomological survey was conducted and ruminant trade-related information was collected. No RVFV RNA was detected out of the 1,568 blood-sucking caught insects, including three potential vectors of RVFV mosquito species. Our trade survey suggests that there is a continuous flow of live animals from eastern Africa to the Union of Comoros and movements of ruminants between the three Comoro islands. Finally, a cross-sectional study was performed in August 2011 at the end of the follow-up. We found an estimated RVFV antibody prevalence of 19.3% (95% CI: [15.6%–23.0%]). Our findings suggest a complex RVFV epidemiological cycle in the Union of Comoros with probable inter-islands differences in RVFV circulation patterns. Moheli, and potentially Anjouan, appear to be acting as endemic reservoir of infection whereas RVFV persistence in Grande Comore could be correlated with trade in live animals with the eastern coast of Africa. More data are needed to estimate the real impact of the disease on human health and on the national economy. PMID:25078616

Geologic history of the Yosemite Valley

USGS Publications Warehouse

Matthes, Francois E.

1930-01-01

Projection of the longitudinal profiles of these hanging valleys forward to the axis of the Merced Canyon shows that they are closely accordant in height. Their profiles indicate a series of points on a former profile of the Merced with respect to which the side streams had graded their courses prior to the last uplift. This old profile can be extended upward into the glaciated part of the Merced Canyon above El Portal and even into the profoundly glaciated Yosemite Valley, accordant points being furnished by a number of hanging side valleys (due allowance being made for glacial erosion suffered by those valleys). However, not all the hanging valleys of the Yosemite region are accordant with this set. Several of them, including the upland valley of Yosemite Creek, constitute a separate set indicating another old profile of the Merced at a level 600 to 1,000 feet higher than the first. Others, including the hanging gulch of lower Bridalveil Creek, point to an old profile of the Merced about 1,200 feet lower than the first. There are thus three distinct sets of hanging valleys produced in three cycles of stream erosion. The valleys of the upper set, like those of the middle set, were left hanging as a result of rapid trenching by the Merced induced by an uplift of the range, there having been two such uplifts. Only the valleys of the lower set hang because of glacial deepening and widening of the Yosemite Valley, the cycle in which they were cut having been interrupted by the advent of the Pleistocene glaciers. They consequently indicate the preglacial depth of the Yosemite Valley. That depth, measured from the brow of El Capitan, was about 2,400 feet; measured from the rim at Glacier Point it was about 2,000 feet.

76 FR 22746 - Conecuh Valley Railway, LLC-Acquisition and Operation Exemption-Conecuh Valley Railroad Co., Inc.

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-22

... Railway, LLC--Acquisition and Operation Exemption--Conecuh Valley Railroad Co., Inc. Conecuh Valley Railway, LLC (CVR), a noncarrier, has filed a verified notice of exemption under 49 CFR 1150.31 to acquire from Conecuh Valley Railroad Co., Inc. (COEH), and to operate [[Page 22747

Coaxial volumetric velocimetry

NASA Astrophysics Data System (ADS)

Schneiders, Jan F. G.; Scarano, Fulvio; Jux, Constantin; Sciacchitano, Andrea

2018-06-01

This study describes the working principles of the coaxial volumetric velocimeter (CVV) for wind tunnel measurements. The measurement system is derived from the concept of tomographic PIV in combination with recent developments of Lagrangian particle tracking. The main characteristic of the CVV is its small tomographic aperture and the coaxial arrangement between the illumination and imaging directions. The system consists of a multi-camera arrangement subtending only few degrees solid angle and a long focal depth. Contrary to established PIV practice, laser illumination is provided along the same direction as that of the camera views, reducing the optical access requirements to a single viewing direction. The laser light is expanded to illuminate the full field of view of the cameras. Such illumination and imaging conditions along a deep measurement volume dictate the use of tracer particles with a large scattering area. In the present work, helium-filled soap bubbles are used. The fundamental principles of the CVV in terms of dynamic velocity and spatial range are discussed. Maximum particle image density is shown to limit tracer particle seeding concentration and instantaneous spatial resolution. Time-averaged flow fields can be obtained at high spatial resolution by ensemble averaging. The use of the CVV for time-averaged measurements is demonstrated in two wind tunnel experiments. After comparing the CVV measurements with the potential flow in front of a sphere, the near-surface flow around a complex wind tunnel model of a cyclist is measured. The measurements yield the volumetric time-averaged velocity and vorticity field. The measurements of the streamlines in proximity of the surface give an indication of the skin-friction lines pattern, which is of use in the interpretation of the surface flow topology.

Grizzly Valley fault system, Sierra Valley, CA

USGS Publications Warehouse

Gold, Ryan; Stephenson, William; Odum, Jack; Briggs, Rich; Crone, Anthony; Angster, Steve

2012-01-01

The Grizzly Valley fault system (GVFS) strikes northwestward across Sierra Valley, California and is part of a network of active, dextral strike-slip faults in the northern Walker Lane (Figure 1). To investigate Quaternary motion across the GVFS, we analyzed high-resolution (0.25 m) airborne LiDAR data (Figure 2) in combination with six, high-resolution, P-wave, seismic-reflection profiles [Gold and others, 2012]. The 0.5- to 2.0-km-long seismic-reflection profiles were sited orthogonal to suspected tectonic lineaments identified from previous mapping and our analysis of airborne LiDAR data. To image the upper 400–700 m of subsurface stratigraphy of Sierra Valley (Figure 3), we used a 230-kg accelerated weight drop source. Geophone spacing ranged from 2 to 5 m and shots were co-located with the geophones. The profiles reveal a highly reflective, deformed basal marker that we interpret to be the top of Tertiary volcanic rocks, overlain by a 120- to 300-m-thick suite of subhorizontal reflectors we interpret as Plio-Pleistocene lacustrine deposits. Three profiles image the principle active trace of the GVFS, which is a steeply dipping fault zone that offsets the volcanic rocks and the basin fill (Figures 4 & 5).

Topological Valley Currents in Gapped Dirac Materials

NASA Astrophysics Data System (ADS)

Lensky, Yuri D.; Song, Justin C. W.; Samutpraphoot, Polnop; Levitov, Leonid S.

2015-06-01

Gapped 2D Dirac materials, in which inversion symmetry is broken by a gap-opening perturbation, feature a unique valley transport regime. Topological valley currents in such materials are dominated by bulk currents produced by electronic states just beneath the gap rather than by edge modes. The system ground state hosts dissipationless persistent valley currents existing even when topologically protected edge modes are absent. Valley currents induced by an external bias are characterized by a quantized half-integer valley Hall conductivity. The undergap currents dominate magnetization and the charge Hall effect in a light-induced valley-polarized state.

Field Surveys, IOC Valleys. Volume III, Part II. Cultural Resources Survey, Pine and Wah Wah Valleys, Utah.

DTIC Science & Technology

1981-08-01

valleys are typical of the Basin and Range Province, characterized by parallel, north-south trending mountain ranges, separated by hydrologically closed... basins . Pine and Wah Wah valleys each have hardpan-playas in their lowest areas. State Highway 21 runs roughly northwest-southeast through both val...have been important for prehis- toric and historic use of the area. Pine Valley: Pine and Wah Wah valleys are closed alluvial basins . The central part

Seroprevalence survey of Egyptian tourism workers for hepatitis B virus, hepatitis C virus, human immunodeficiency virus, and Treponema pallidum infections: association of hepatitis C virus infections with specific regions of Egypt.

PubMed

el-Sayed, N M; Gomatos, P J; Rodier, G R; Wierzba, T F; Darwish, A; Khashaba, S; Arthur, R R

1996-08-01

Blood samples from 740 Egyptian Nationals working in the tourism industry at two sites in the South Sinai governorate were screened for markers of infection with hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), and Treponema pallidum. Study subjects included 467 individuals from a rural seashore tourist village and 273 persons at two hotels in a well-established resort town. Subjects' ages ranged from 15 to 70 years; 99.3% were male. The prevalence of serologic markers for currently asymptomatic or past HBV infection alone was 20.7% (n = 153), of markers for past or chronic HCV infection alone was 7.4% (n = 55), and of markers for both HBV and HCV was 6.9% (n = 51). Of the 204 individuals positive for anti-HBV core antibody, 12 (5.9%) were also positive for hepatitis B surface antigen. Two individuals (0.3%) had a serologic market suggestive of an active syphilitic infection. No subject was found to be HIV-seropositive. History of prior injections and number of injections were associated with infection with HCV. Primary residence in the Nile delta and valley areas where schistosomiasis is highly endemic, was also a statistically significant risk factor for HCV, but not HBV infection.

A landscape scale valley confinement algorithm: Delineating unconfined valley bottoms for geomorphic, aquatic, and riparian applications

Treesearch

David E. Nagel; John M. Buffington; Sharon L. Parkes; Seth Wenger; Jaime R. Goode

2014-01-01

Valley confinement is an important landscape characteristic linked to aquatic habitat, riparian diversity, and geomorphic processes. This report describes a GIS program called the Valley Confinement Algorithm (VCA), which identifies unconfined valleys in montane landscapes. The algorithm uses nationally available digital elevation models (DEMs) at 10-30 m resolution to...

Graphene Nanobubbles as Valley Filters and Beam Splitters

NASA Astrophysics Data System (ADS)

Settnes, Mikkel; Power, Stephen R.; Brandbyge, Mads; Jauho, Antti-Pekka

2016-12-01

The energy band structure of graphene has two inequivalent valleys at the K and K' points of the Brillouin zone. The possibility to manipulate this valley degree of freedom defines the field of valleytronics, the valley analogue of spintronics. A key requirement for valleytronic devices is the ability to break the valley degeneracy by filtering and spatially splitting valleys to generate valley polarized currents. Here, we suggest a way to obtain valley polarization using strain-induced inhomogeneous pseudomagnetic fields (PMFs) that act oppositely on the two valleys. Notably, the suggested method does not involve external magnetic fields, or magnetic materials, unlike previous proposals. In our proposal the strain is due to experimentally feasible nanobubbles, whose associated PMFs lead to different real space trajectories for K and K' electrons, thus allowing the two valleys to be addressed individually. In this way, graphene nanobubbles can be exploited in both valley filtering and valley splitting devices, and our simulations reveal that a number of different functionalities are possible depending on the deformation field.

Historical Perspective: What Constitutes Discovery (of a New Virus)?

PubMed

Murphy, F A

2016-01-01

A historic review of the discovery of new viruses leads to reminders of traditions that have evolved over 118 years. One such tradition gives credit for the discovery of a virus to the investigator(s) who not only carried out the seminal experiments but also correctly interpreted the findings (within the technological context of the day). Early on, ultrafiltration played a unique role in "proving" that an infectious agent was a virus, as did a failure to find any microscopically visible agent, failure to show replication of the agent in the absence of viable cells, thermolability of the agent, and demonstration of a specific immune response to the agent so as to rule out duplicates and close variants. More difficult was "proving" that the new virus was the etiologic agent of the disease ("proof of causation")-for good reasons this matter has been revisited several times over the years as technologies and perspectives have changed. One tradition is that the discoverers get to name their discovery, their new virus (unless some grievous convention has been broken)-the stability of these virus names has been a way to honor the discoverer(s) over the long term. Several vignettes have been chosen to illustrate several difficulties in holding to the traditions (vignettes chosen include vaccinia and variola viruses, yellow fever virus, and influenza viruses. Crimean-Congo hemorrhagic fever virus, Murray Valley encephalitis virus, human immunodeficiency virus 1, Sin Nombre virus, and Ebola virus). Each suggests lessons for the future. One way to assure that discoveries are forever linked with discoverers would be a permanent archive in one of the universal virus databases that have been constructed for other purposes. However, no current database seems ideal-perhaps members of the global community of virologists will have an ideal solution. © 2016 Elsevier Inc. All rights reserved.

The Long Valley Caldera GIS database

USGS Publications Warehouse

Battaglia, Maurizio; Williams, M.J.; Venezky, D.Y.; Hill, D.P.; Langbein, J.O.; Farrar, C.D.; Howle, J.F.; Sneed, M.; Segall, P.

2003-01-01

This database provides an overview of the studies being conducted by the Long Valley Observatory in eastern California from 1975 to 2001. The database includes geologic, monitoring, and topographic datasets related to Long Valley caldera. The CD-ROM contains a scan of the original geologic map of the Long Valley region by R. Bailey. Real-time data of the current activity of the caldera (including earthquakes, ground deformation and the release of volcanic gas), information about volcanic hazards and the USGS response plan are available online at the Long Valley observatory web page (http://lvo.wr.usgs.gov). If you have any comments or questions about this database, please contact the Scientist in Charge of the Long Valley observatory.

A Rift Valley Fever Vaccine Trial. 1. Side Effects and Serologic Response Over a Six-Month Follow-Up

DTIC Science & Technology

1982-01-01

strep - injection. One volunteer was excluded tomycin and 10 per cent fetal calf serum. from the trial following detection of se- The cells were...ml swelling, induration) were recorded. Each of lot 1. Three additional individuals who symptom was individually scored on a received the 1 ml dose...plaque-forming units of the tivities, nasal discharge, sore throat , ZH501 strain of Rift Valley fever virus cough, nausea or anorexia, vomiting, and and

Toscana virus induces interferon although its NSs protein reveals antagonistic activity.

PubMed

Gori Savellini, Gianni; Weber, Friedemann; Terrosi, Chiara; Habjan, Matthias; Martorelli, Barbara; Cusi, Maria Grazia

2011-01-01

Toscana virus (TOSV) is a phlebotomus-transmitted virus that belongs to the family Bunyaviridae and causes widespread infections in humans; about 30 % of these cases result in aseptic meningitis. In the present study, it was shown that TOSV is an inducer of beta interferon (IFN-β), although its non-structural protein (NSs) could inhibit the induction of IFN-β if expressed in a heterologous context. A recombinant Rift Valley fever virus expressing the TOSV NSs could suppress IFN-β expression in infected cells. Moreover, in cells expressing NSs protein from a cDNA plasmid, IFN-β transcripts were not inducible by poly(I : C). Unlike other members of the family Bunyaviridae, TOSV appears to express an NSs protein that is a weak antagonist of IFN induction. Characterization of the interaction of TOSV with the IFN system will help our understanding of virus-host cell interactions and may explain why the pathogenesis of this disease is mostly mild in humans.

RNA Viruses that Cause Hemorrhagic, Encephalitic, and Febrile Disease

DTIC Science & Technology

1990-01-01

doses to levels that are subopti- effective dose (ED,0) values for Rift Valley mal for cures in other bunyavirus mouse Fever ( RVF ) virus (ED,, = 80 g...serum protein and AST Etiologic Agent (SGOT) identified in the placebo group by logistic regression], utilizing a stepwise lo- RVF , an old-world...treatment of H FRS in this study. Treatment reduced mortality RVF , distributed throughout sub-Saharan and improved several important aspects of Africa

27 CFR 9.78 - Ohio River Valley.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Ohio River Valley. 9.78... River Valley. (a) Name. The name of the viticultural area described in this section is “Ohio River Valley.” (b) Approved maps. The approved maps for determining the boundary of the Ohio River Valley...

Valley dependent transport in graphene L junction

NASA Astrophysics Data System (ADS)

Chan, K. S.

2018-05-01

We studied the valley dependent transport in graphene L junctions connecting an armchair lead and a zigzag lead. The junction can be used in valleytronic devices and circuits. Electrons injected from the armchair lead into the junction is not valley polarized, but they can become valley polarized in the zigzag lead. There are Fermi energies, where the current in the zigzag lead is highly valley polarized and the junction is an efficient generator of valley polarized current. The features of the valley polarized current depend sensitively on the widths of the two leads, as well as the number of dimers in the armchair lead, because this number has a sensitive effect on the band structure of the armchair lead. When an external potential is applied to the junction, the energy range with high valley polarization is enlarged enhancing its function as a generator of highly valley polarized current. The scaling behavior found in other graphene devices is also found in L junctions, which means that the results presented here can be extended to junctions with larger dimensions after appropriate scaling of the energy.

Down in the Valley.

ERIC Educational Resources Information Center

Salter, Linda Graef

1999-01-01

Describes the partnerships formed by West Valley Mission Community College District (California) with its surrounding Silicon Valley business community in an effort to benefit workforce development. Asserts that community colleges are uniquely positioned to provide a lifelong education that will yield a skilled workforce to meet the needs of…

Hazardous Waste Cleanup: West Valley Demonstration Project USDOE in West Valley, New York

EPA Pesticide Factsheets

The U.S. Department of Energy's West Valley Demonstration Project is located at 10282 Rock Spring Road in West Valley, New York. This is a 167 acre, Department of Energy (DOE)-operated portion of a 3,300-acre site owned by the New York State Energy

9 CFR 121.4 - Overlap select agents and toxins.

Code of Federal Regulations, 2011 CFR

2011-01-01

...; Hendra virus; Nipah virus; Rift Valley fever virus; Venezuelan equine encephalitis virus. (c) Genetic... melitensis, Hendra virus, Nipah virus, Rift Valley fever virus, and Venezuelan equine encephalitis virus...

Chimpanzee Adenovirus Vaccine Provides Multispecies Protection against Rift Valley Fever.

PubMed

Warimwe, George M; Gesharisha, Joseph; Carr, B Veronica; Otieno, Simeon; Otingah, Kennedy; Wright, Danny; Charleston, Bryan; Okoth, Edward; Elena, Lopez-Gil; Lorenzo, Gema; Ayman, El-Behiry; Alharbi, Naif K; Al-dubaib, Musaad A; Brun, Alejandro; Gilbert, Sarah C; Nene, Vishvanath; Hill, Adrian V S

2016-02-05

Rift Valley Fever virus (RVFV) causes recurrent outbreaks of acute life-threatening human and livestock illness in Africa and the Arabian Peninsula. No licensed vaccines are currently available for humans and those widely used in livestock have major safety concerns. A 'One Health' vaccine development approach, in which the same vaccine is co-developed for multiple susceptible species, is an attractive strategy for RVFV. Here, we utilized a replication-deficient chimpanzee adenovirus vaccine platform with an established human and livestock safety profile, ChAdOx1, to develop a vaccine for use against RVFV in both livestock and humans. We show that single-dose immunization with ChAdOx1-GnGc vaccine, encoding RVFV envelope glycoproteins, elicits high-titre RVFV-neutralizing antibody and provides solid protection against RVFV challenge in the most susceptible natural target species of the virus-sheep, goats and cattle. In addition we demonstrate induction of RVFV-neutralizing antibody by ChAdOx1-GnGc vaccination in dromedary camels, further illustrating the potency of replication-deficient chimpanzee adenovirus vaccine platforms. Thus, ChAdOx1-GnGc warrants evaluation in human clinical trials and could potentially address the unmet human and livestock vaccine needs.

Dengue Hemorrhagic Fever Virus in Saudi Arabia: A Review.

PubMed

Al-Tawfiq, Jaffar A; Memish, Ziad A

2018-02-01

Dengue fever is a global disease with a spectrum of clinical manifestation ranging from mild febrile disease to a severe disease in the form of dengue hemorrhagic fever and dengue shock syndrome. Dengue virus is one viral hemorrhagic fever that exists in the Kingdom of Saudi Arabia in addition to Alkhurma (Alkhurma) Hemorrhagic Fever, Chikungunya virus, Crimean-Congo Hemorrhagic Fever, and Rift Valley Fever. The disease is limited to the Western and South-western regions of Saudi Arabia, where Aedes aegypti exists. The majority of the cases in Saudi Arabia had mild disease and is related to serotypes 1-3 but not 4. The prospect for Dengue virus control relies on vector control, health education, and possibly vaccine use. Despite extensive collaborative efforts between multiple governmental sectors, including Ministry of Health, Ministry of Municipalities and Rural Affairs, and Ministry of Water, dengue remains a major public health concern in the regions affected.

An evaluation of Skylab (EREP) remote sensing techniques applied to investigation of crustal structure. [Death Valley and Greenwater Valley (CA)

NASA Technical Reports Server (NTRS)

Bechtold, I. C. (Principal Investigator)

1974-01-01

The author has identified the following significant results. A study of Greenwater Valley indicates that the valley is bounded on the north and east by faults, on the south by a basement high, and on the west by the dip slope of the black mountains, movement of ground water from the valley is thus Movement of ground water from the valley is thus restricted, indicating the valley is a potential water reservoir.

Rift Valley Fever, Sudan, 2007 and 2010

PubMed Central

Aradaib, Imadeldin E.; Erickson, Bobbie R.; Elageb, Rehab M.; Khristova, Marina L.; Carroll, Serena A.; Elkhidir, Isam M.; Karsany, Mubarak E.; Karrar, AbdelRahim E.; Elbashir, Mustafa I.

2013-01-01

To elucidate whether Rift Valley fever virus (RVFV) diversity in Sudan resulted from multiple introductions or from acquired changes over time from 1 introduction event, we generated complete genome sequences from RVFV strains detected during the 2007 and 2010 outbreaks. Phylogenetic analyses of small, medium, and large RNA segment sequences indicated several genetic RVFV variants were circulating in Sudan, which all grouped into Kenya-1 or Kenya-2 sublineages from the 2006–2008 eastern Africa epizootic. Bayesian analysis of sequence differences estimated that diversity among the 2007 and 2010 Sudan RVFV variants shared a most recent common ancestor circa 1996. The data suggest multiple introductions of RVFV into Sudan as part of sweeping epizootics from eastern Africa. The sequences indicate recent movement of RVFV and support the need for surveillance to recognize when and where RVFV circulates between epidemics, which can make data from prediction tools easier to interpret and preventive measures easier to direct toward high-risk areas. PMID:23347790

Prediction of a Rift Valley fever outbreak

PubMed Central

Anyamba, Assaf; Chretien, Jean-Paul; Small, Jennifer; Tucker, Compton J.; Formenty, Pierre B.; Richardson, Jason H.; Britch, Seth C.; Schnabel, David C.; Erickson, Ralph L.; Linthicum, Kenneth J.

2009-01-01

El Niño/Southern Oscillation related climate anomalies were analyzed by using a combination of satellite measurements of elevated sea-surface temperatures and subsequent elevated rainfall and satellite-derived normalized difference vegetation index data. A Rift Valley fever (RVF) risk mapping model using these climate data predicted areas where outbreaks of RVF in humans and animals were expected and occurred in the Horn of Africa from December 2006 to May 2007. The predictions were subsequently confirmed by entomological and epidemiological field investigations of virus activity in the areas identified as at risk. Accurate spatial and temporal predictions of disease activity, as it occurred first in southern Somalia and then through much of Kenya before affecting northern Tanzania, provided a 2 to 6 week period of warning for the Horn of Africa that facilitated disease outbreak response and mitigation activities. To our knowledge, this is the first prospective prediction of a RVF outbreak. PMID:19144928

Rift Valley Fever Seroprevalence in Coastal Kenya.

PubMed

Grossi-Soyster, Elysse N; Banda, Tamara; Teng, Crystal Y; Muchiri, Eric M; Mungai, Peter L; Mutuku, Francis M; Gildengorin, Ginny; Kitron, Uriel; King, Charles H; Desiree Labeaud, A

2017-07-01

Rift Valley fever virus (RVFV) causes severe disease in both animals and humans, resulting in significant economic and public health damages. The objective of this study was to measure RVFV seroprevalence in six coastal Kenyan villages between 2009 and 2011, and characterize individual-, household-, and community-level risk factors for prior RVFV exposure. Sera were tested for anti-RVFV IgG via enzyme-linked immunosorbent assay. Overall, 51 (1.8%; confidence interval [CI 95 ] 1.3-2.3) of 2,871 samples were seropositive for RVFV. Seroprevalence differed significantly among villages, and was highest in Jego Village (18/300; 6.0%; CI 95 3.6-9.3) and lowest in Magodzoni (0/248). Adults were more likely to be seropositive than children ( P < 0.001). Seropositive subjects were less likely to own land or a motor vehicle ( P < 0.01), suggesting exposure is associated with lower socioeconomic standing ( P = 0.03). RVFV exposure appears to be low in coastal Kenya, although with some variability among villages.

27 CFR 9.154 - Chiles Valley.

Code of Federal Regulations, 2013 CFR

2013-04-01

... Chiles Valley. (a) Name. The name of the viticultural area described in this section is “Chiles Valley... viticultural area are four 1:24,000 Scale U.S.G.S. topography maps. They are titled: (1) St. Helena, CA 1960 photorevised 1980; (2) Rutherford, CA 1951 photorevised 1968; (3) Chiles Valley, CA 1958 photorevised 1980; (4...

Meter-Scale Characteristics of Martian Channels and Valleys

USGS Publications Warehouse

Carr, M.H.; Malin, M.C.

2000-01-01

Mars Global Surveyor images, with resolutions as high as 1.5 m pixel, enable characterization of martian channels and valleys at resolutions one to two orders of magnitude better than was previously possible. A major surprise is the near-absence of valleys a few hundred meters wide and narrower. The almost complete absence of fine-scale valleys could be due to lack of precipitation, destruction of small valleys by erosion, or dominance of infiltration over surface runoff. V-shaped valleys with a central channel, such as Nanedi Vallis, provide compelling evidence for sustained or episodic flow of water across the surface. Larger valleys appear to have formed not by headward erosion as a consequence of groundwater sapping but by erosion from water sources upstream of the observed sections. The freshest appearing valleys have triangular cross sections, with talus from opposing walls meeting at the center of the valley. The relations suggest that the width of the valleys is controlled by the depth of incision and the angle of repose of the walls. The flat floors of less fresh-appearing valleys result primarily from later eolian fill. Several discontinuous valleys and lines of craters suggest massive subsurface solution or erosion. The climatic implications of the new images will remain obscure until the cause for the scarcity of fine-scale dissection is better understood. ?? 2000 Academic Press.

An investigation of duck circovirus and co-infection in Cherry Valley ducks in Shandong Province, China.

PubMed

Zhang, Xingxiao; Jiang, Shijin; Wu, Jiaqiang; Zhao, Qin; Sun, Yani; Kong, Yibo; Li, Xiaoxia; Yao, Meiling; Chai, Tongjie

2009-01-13

The co-infection of duck circovirus (DuCV) with Riemerella anatipestifer (RA) or/and Escherichia coli (E. coli) or/and duck hepatitis virus I (DHV-I) in Cherry Valley ducks in China's Shandong Province was investigated by using polymerase-chain-reaction (PCR)-based methods. For this study, 742 ducks sampled at random from 70 duck farms during 2006-2007 were examined using PCR and dot-blot hybridisation (DBH) tests. Overall the DuCV infection rate was 33.29%. Compared with those at 2 weeks of age, the ducks at 3-4 weeks of age were more susceptible to DuCV infection. Compared with the DuCV-negative ones, the DuCV-positive ducks had a higher rate of infection by DHV-I (25.5% vs. 7.475%), RA (23.48% vs. 8.28%) and E. coli (16.19% vs. 4.85%). This investigation shows that DuCV infection is common in Cherry Valley ducks on some farms in Shandong Province.

Detection of Rift Valley fever viral activity in Kenya by satellite remote sensing imagery

NASA Technical Reports Server (NTRS)

Linthicum, Kenneth J.; Bailey, Charles L.; Davies, F. Glyn; Tucker, Compton J.

1987-01-01

Data from the advanced very high resolution radiometer on board the National Oceanic and Atmospheric Administration's polar-orbiting meteorological satellites have been used to infer ecological parameters associated with Rift Valley fever (RVF) viral activity in Kenya. An indicator of potential viral activity was produced from satellite data for two different ecological regions in Kenya, where RVF is enzootic. The correlation between the satellite-derived green vegetation index and the ecological parameters associated with RVF virus suggested that satellite data may become a forecasting tool for RVF in Kenya and, perhaps, in other areas of sub-Saharan Africa.

Microscopic Identification of Prokaryotes in Modern and Ancient Halite, Saline Valley and Death Valley, California

NASA Astrophysics Data System (ADS)

Schubert, Brian A.; Lowenstein, Tim K.; Timofeeff, Michael N.

2009-06-01

Primary fluid inclusions in halite crystallized in Saline Valley, California, in 1980, 2004-2005, and 2007, contain rod- and coccoid-shaped microparticles the same size and morphology as archaea and bacteria living in modern brines. Primary fluid inclusions from a well-dated (0-100,000 years), 90 m long salt core from Badwater Basin, Death Valley, California, also contain microparticles, here interpreted as halophilic and halotolerant prokaryotes. Prokaryotes are distinguished from crystals on the basis of morphology, optical properties (birefringence), and uniformity of size. Electron micrographs of microparticles from filtered modern brine (Saline Valley), dissolved modern halite crystals (Saline Valley), and dissolved ancient halite crystals (Death Valley) support in situ microscopic observations that prokaryotes are present in fluid inclusions in ancient halite. In the Death Valley salt core, prokaryotes in fluid inclusions occur almost exclusively in halite precipitated in perennial saline lakes 10,000 to 35,000 years ago. This suggests that trapping and preservation of prokaryotes in fluid inclusions is influenced by the surface environment in which the halite originally precipitated. In all cases, prokaryotes in fluid inclusions in halite from the Death Valley salt core are miniaturized (<1 μm diameter cocci, <2.5 μm long, very rare rod shapes), which supports interpretations that the prokaryotes are indigenous to the halite and starvation survival may be the normal response of some prokaryotes to entrapment in fluid inclusions for millennia. These results reinforce the view that fluid inclusions in halite and possibly other evaporites are important repositories of microbial life and should be carefully examined in the search for ancient microorganisms on Earth, Mars, and elsewhere in the Solar System.

Valley Vortex States in Sonic Crystals

NASA Astrophysics Data System (ADS)

Lu, Jiuyang; Qiu, Chunyin; Ke, Manzhu; Liu, Zhengyou

2016-03-01

Valleytronics is quickly emerging as an exciting field in fundamental and applied research. In this Letter, we study the acoustic version of valley states in sonic crystals and reveal a vortex nature of such states. In addition to the selection rules established for exciting valley polarized states, a mimicked valley Hall effect of sound is proposed further. The extraordinary chirality of valley vortex states, detectable in experiments, may open a new possibility in sound manipulations. This is appealing to scalar acoustics that lacks a spin degree of freedom inherently. In addition, the valley selection enables a handy way to create vortex matter in acoustics, in which the vortex chirality can be controlled flexibly. Potential applications can be anticipated with the exotic interaction of acoustic vortices with matter, such as to trigger the rotation of the trapped microparticles without contact.

Topological Valley Transport in Two-dimensional Honeycomb Photonic Crystals.

PubMed

Yang, Yuting; Jiang, Hua; Hang, Zhi Hong

2018-01-25

Two-dimensional photonic crystals, in analogy to AB/BA stacking bilayer graphene in electronic system, are studied. Inequivalent valleys in the momentum space for photons can be manipulated by simply engineering diameters of cylinders in a honeycomb lattice. The inequivalent valleys in photonic crystal are selectively excited by a designed optical chiral source and bulk valley polarizations are visualized. Unidirectional valley interface states are proved to exist on a domain wall connecting two photonic crystals with different valley Chern numbers. With the similar optical vortex index, interface states can couple with bulk valley polarizations and thus valley filter and valley coupler can be designed. Our simple dielectric PC scheme can help to exploit the valley degree of freedom for future optical devices.

Optical tuning of electronic valleys (Conference Presentation)

NASA Astrophysics Data System (ADS)

Sie, Edbert J.; Gedik, Nuh

2017-02-01

Monolayer transition-metal dichalcogenides such as MoS2 and WS2 are prime examples of atomically thin semiconducting crystals that exhibit remarkable electronic and optical properties. They have a pair of valleys that can serve as a new electronic degree of freedom, and these valleys obey optical selection rules with circularly polarized light. Here, we discuss how ultrafast laser pulses can be used to tune their energy levels in a controllable valley-selective manner. The energy tunability is extremely large, comparable to what would be obtained using a hundred Tesla of magnetic field. We will also show that such valley tunability can be performed while we effectively manipulate the valley selection rules. Finally, we will explore the prospect of using this technique through photoemission spectroscopy to create a new phase of matter called a valley Floquet topological insulator.

Martian oceans, valleys and climate

USGS Publications Warehouse

Carr, M.H.

2000-01-01

The new Mars Global Surveyor altimetry shows that the heavily cratered southern hemisphere of Mars is 5 km higher that the sparely cratered plains of the northern hemisphere. Previous suggestions that oceans formerly occupied that northern plains as evidenced by shorelines are partly supported by the new data. A previously identified outer boundary has a wide range of elevations and is unlikely to be a shoreline but an inner contact with a narrow range of elevations is a more likely candidate. No shorelines are visible in the newly acquired, 2.5 metre/pixel imaging. Newly imaged valleys provide strong support for sustained or episodic flow of water across the Martian surface. A major surprise, however, is the near absence of valleys less than 100 m across. Martian valleys seemingly do not divide into ever smaller valleys as terrestrial valleys commonly do. This could be due to lack of precipitation or lack of surface runoff because of high infiltration rates. High erosion rates and supports warm climates and presence of large bodies of water during heavy bombardment. The climate history and fate of the water after heavy bombardment remain cotroversial.

Knickpoints and Hanging Valleys of Licus Vallis, Mars

NASA Astrophysics Data System (ADS)

Goudge, T. A.; Fassett, C.

2016-12-01

Licus Vallis is a 350 km long valley system located along the dichotomy boundary on Mars. The main trunk of the valley is incised 200-700 m into the surrounding terrain. The valley heads at an outlet breach of a shallow, 30 km diameter impact crater, and is also fed by a system of tributaries incised into the plateau surrounding Licus Vallis. Many of the tributary valleys, as well as the main stem of the valley fed by the paleolake outlet, have profiles that are not smoothly graded, but rather have distinct reaches with concave downward topography. These sections are either knickpoints or hanging valleys that develop in response to changes in the effective local base level, changes in climate conditions during incision of the valley, or lithologic boundaries in the substrate. Here we present remote sensing observations from images and topography to test these competing hypotheses and further characterize the evolution of this large valley system. Slope-watershed area relationships for the tributaries and main trunk valley are used to distinguish between knickpoints and hanging valleys. Analysis of orbital images does not reveal any distinct layer above which knickpoints develop, and the elevation of knickpoints show no systematic trends that might be expected of a regional lithologic unit(s). Our preliminary results suggest that the distance of knickpoint retreat is correlated with the position of the tributary valley and not the watershed area. Downstream valleys have retreated the most, suggesting they have had the most time to adjust to lowering of the local base level associated with incision of the main valley. These results are most consistent with a wave of incision sweeping up the valley system as it adjusts to a low base level in the northern plains. This conclusion is also consistent with observations of the incision depth of Licus Vallis, which increases approximately linearly downstream. Understanding this signature of base level control on the incision

The Example of Eastern Africa: the dynamic of Rift Valley fever and tools for monitoring virus activity

USDA-ARS?s Scientific Manuscript database

Rift Valley fever is a mosquito-borne viral zoonosis that primarily affects animals but also has the capacity to infect humans. Outbreaks of this disease in eastern Africa are closely associated with periods of heavy rainfall and forecasting models and early warning systems have been developed to en...

Magnetic control of valley pseudospin in monolayer WSe 2

DOE PAGES

Aivazian, G.; Gong, Zhirui; Jones, Aaron M.; ...

2015-01-26

Local energy extrema of the bands in momentum space, or valleys, can endow electrons in solids with pseudo-spin in addition to real spin 1-5. In transition metal dichalcogenides this valley pseudo-spin, like real spin, is associated with a magnetic moment1,6 which underlies the valley-dependent circular dichroism 6 that allows optical generation of valley polarization 7-9, intervalley quantum coherence 10, and the valley Hall effect 11. However, magnetic manipulation of valley pseudospin via this magnetic moment 12-13, analogous to what is possible with real spin, has not been shown before. Here we report observation of the valley Zeeman splitting and magneticmore » tuning of polarization and coherence of the excitonic valley pseudospin, by performing polarization-resolved magneto-photoluminescence on monolayer WSe 2. Our measurements reveal both the atomic orbital and lattice contributions to the valley orbital magnetic moment; demonstrate the deviation of the band edges in the valleys from an exact massive Dirac fermion model; and reveal a striking difference between the magnetic responses of neutral and charged valley excitons which is explained by renormalization of the excitonic spectrum due to strong exchange interactions.« less

Spin and valley filter across line defect in silicene

NASA Astrophysics Data System (ADS)

Wang, Sake; Ren, Chongdan; Li, Yunfang; Tian, Hongyu; Lu, Weitao; Sun, Minglei

2018-05-01

We propose a new scheme to achieve an effective spin/valley filter in silicene with extended line defect on the basis of spin–valley coupling due to the intrinsic spin-orbit coupling (SOC). The transmission coefficient of the spin/valley states is seriously affected by the SOC. When a perpendicular magnetic field is applied on one side of the line defect, one valley state will experience backscattering, but the other valley will not; this leads to high valley polarization in all transmission directions. Moreover, the spin/valley polarization can be enhanced to 96% with the aid of a perpendicular electric field.

Toscana virus NSs protein promotes degradation of double-stranded RNA-dependent protein kinase.

PubMed

Kalveram, Birte; Ikegami, Tetsuro

2013-04-01

Toscana virus (TOSV), which is transmitted by Phlebotomus spp. sandflies, is a major etiologic agent of aseptic meningitis and encephalitis in the Mediterranean. Like other members of the genus Phlebovirus of the family Bunyaviridae, TOSV encodes a nonstructural protein (NSs) in its small RNA segment. Although the NSs of Rift Valley fever virus (RVFV) has been identified as an important virulence factor, which suppresses host general transcription, inhibits transcription from the beta interferon promoter, and promotes the proteasomal degradation of double-stranded RNA-dependent protein kinase (PKR), little is known about the functions of NSs proteins encoded by less-pathogenic members of this genus. In this study we report that TOSV is able to downregulate PKR with similar efficiency as RVFV, while infection with the other phleboviruses-i.e., Punta Toro virus, sandfly fever Sicilian virus, or Frijoles virus-has no effect on cellular PKR levels. In contrast to RVFV, however, cellular transcription remains unaffected during TOSV infection. TOSV NSs protein promotes the proteasome-dependent downregulation of PKR and is able to interact with kinase-inactive PKR in infected cells.

Rift Valley Fever Virus MP-12 Vaccine Is Fully Attenuated by a Combination of Partial Attenuations in the S, M, and L Segments

PubMed Central

Hill, Terence E.; Smith, Jennifer K.; Zhang, Lihong; Juelich, Terry L.; Gong, Bin; Slack, Olga A. L.; Ly, Hoai J.; Lokugamage, Nandadeva; Freiberg, Alexander N.

2015-01-01

ABSTRACT Rift Valley fever (RVF) is a mosquito-borne zoonotic disease endemic to Africa and characterized by a high rate of abortion in ruminants and hemorrhagic fever, encephalitis, or blindness in humans. RVF is caused by Rift Valley fever virus (RVFV; family Bunyaviridae, genus Phlebovirus), which has a tripartite negative-stranded RNA genome (consisting of the S, M, and L segments). Further spread of RVF into countries where the disease is not endemic may affect the economy and public health, and vaccination is an effective approach to prevent the spread of RVFV. A live-attenuated MP-12 vaccine is one of the best-characterized RVF vaccines for safety and efficacy and is currently conditionally licensed for use for veterinary purposes in the United States. Meanwhile, as of 2015, no other RVF vaccine has been conditionally or fully licensed for use in the United States. The MP-12 strain is derived from wild-type pathogenic strain ZH548, and its genome encodes 23 mutations in the three genome segments. However, the mechanism of MP-12 attenuation remains unknown. We characterized the attenuation of wild-type pathogenic strain ZH501 carrying a mutation(s) of the MP-12 S, M, or L segment in a mouse model. Our results indicated that MP-12 is attenuated by the mutations in the S, M, and L segments, while the mutations in the M and L segments confer stronger attenuation than those in the S segment. We identified a combination of 3 amino acid changes, Y259H (Gn), R1182G (Gc), and R1029K (L), that was sufficient to attenuate ZH501. However, strain MP-12 with reversion mutations at those 3 sites was still highly attenuated. Our results indicate that MP-12 attenuation is supported by a combination of multiple partial attenuation mutations and a single reversion mutation is less likely to cause a reversion to virulence of the MP-12 vaccine. IMPORTANCE Rift Valley fever (RVF) is a mosquito-transmitted viral disease that is endemic to Africa and that has the potential to

Rift Valley Fever Virus MP-12 Vaccine Is Fully Attenuated by a Combination of Partial Attenuations in the S, M, and L Segments.

PubMed

Ikegami, Tetsuro; Hill, Terence E; Smith, Jennifer K; Zhang, Lihong; Juelich, Terry L; Gong, Bin; Slack, Olga A L; Ly, Hoai J; Lokugamage, Nandadeva; Freiberg, Alexander N

2015-07-01

Rift Valley fever (RVF) is a mosquito-borne zoonotic disease endemic to Africa and characterized by a high rate of abortion in ruminants and hemorrhagic fever, encephalitis, or blindness in humans. RVF is caused by Rift Valley fever virus (RVFV; family Bunyaviridae, genus Phlebovirus), which has a tripartite negative-stranded RNA genome (consisting of the S, M, and L segments). Further spread of RVF into countries where the disease is not endemic may affect the economy and public health, and vaccination is an effective approach to prevent the spread of RVFV. A live-attenuated MP-12 vaccine is one of the best-characterized RVF vaccines for safety and efficacy and is currently conditionally licensed for use for veterinary purposes in the United States. Meanwhile, as of 2015, no other RVF vaccine has been conditionally or fully licensed for use in the United States. The MP-12 strain is derived from wild-type pathogenic strain ZH548, and its genome encodes 23 mutations in the three genome segments. However, the mechanism of MP-12 attenuation remains unknown. We characterized the attenuation of wild-type pathogenic strain ZH501 carrying a mutation(s) of the MP-12 S, M, or L segment in a mouse model. Our results indicated that MP-12 is attenuated by the mutations in the S, M, and L segments, while the mutations in the M and L segments confer stronger attenuation than those in the S segment. We identified a combination of 3 amino acid changes, Y259H (Gn), R1182G (Gc), and R1029K (L), that was sufficient to attenuate ZH501. However, strain MP-12 with reversion mutations at those 3 sites was still highly attenuated. Our results indicate that MP-12 attenuation is supported by a combination of multiple partial attenuation mutations and a single reversion mutation is less likely to cause a reversion to virulence of the MP-12 vaccine. Rift Valley fever (RVF) is a mosquito-transmitted viral disease that is endemic to Africa and that has the potential to spread into other

Viruses of the Bunya- and Togaviridae families: potential as bioterrorism agents and means of control.

PubMed

Sidwell, Robert W; Smee, Donald F

2003-01-01

When considering viruses of potential importance as tools for bioterrorism, several viruses in the Bunya- and Togaviridae families have been cited. Among those in the Bunyaviridae family are Rift Valley fever, Crimean-Congo hemorrhagic fever, hanta, and sandfly fever viruses, listed in order of priority. Those particularly considered in the Togaviridae family are Venezuelan, eastern and western equine encephalitis viruses. Factors affecting the selection of these viruses are the ability for them to induce a fatal or seriously incapacitating illness, their ease of cultivation in order to prepare large volumes, their relative infectivity in human patients, their ability to be transmitted by aerosol, and the lack of measures available for their control. Each factor is fully considered in this review. Vaccines for the control of infections induced by these viruses are in varying stages of development, with none universally accepted to date. Viruses in the Bunyaviridae family are generally sensitive to ribavirin, which has been recommended as an emergency therapy for infections by viruses in this family although has not yet been FDA-approved. Interferon and interferon inducers also significantly inhibit these virus infections in animal models. Against infections induced by viruses in the Togaviridae family, interferon-alpha would appear to currently be the most useful for therapy.

Neutralizing monoclonal antibodies recognize antigenic variants among isolates of infectious hematopoietic necrosis virus

USGS Publications Warehouse

Winton, J.R.; Arakawa, C.N.; Lannan, C.N.; Fryer, J.L.

1988-01-01

eutralizing monoclonal antibodies were developed against strains of infectious hematopoietic necrosis virus (IHNV) from steelhead trout Salmo gairdneri in the Deschutes River of Oregon, chinook salmon Oncorhynchus tshawytscha in the Sacramento River of California, and rainbow trout Salmo gairdneri reared in the Hagerman Valley of Idaho, USA. These antibodies were tested for neutralization of 12 IHNV isolates obtained from salmonids in Japan, Alaska, Washington, Oregon, California, and Idaho. The antibodies recognized antigenic variants among the isolates and could be used to separate the viruses into 4 groups. The members of each group tended to be related by geographic area rather than by source host species, virulence, or date of isolation.

Development of a duplex semi-nested PCR assay for detection of classical goose parvovirus and novel goose parvovirus-related virus in sick or dead ducks with short beak and dwarfism syndrome.

PubMed

Li, Pengfei; Zhang, Ruihua; Chen, Junhao; Sun, Dapeng; Lan, Jingjing; Lin, Shaoli; Song, Shasha; Xie, Zhijing; Jiang, Shijin

2017-11-01

Duck short beak and dwarfism syndrome (SBDS) is an emerging infectious disease caused by a novel goose parvovirus-related virus (NGPV) in China. Until now, it remains uncertain whether the Cherry Valley ducks and mule ducks with SBDS are co-infected with classical goose parvovirus (GPV) and NGPV. In this study, a duplex semi-nested PCR assay with high specificity and sensitivity was developed for detection of the two viruses. Using the duplex PCR assay, NGPV was tested positive in all the 15 duck flocks with SBDS, whereas classical GPV was not detected in all the 133 sick and dead ducks collected from East China. A total of 87 (91.58%) Cherry Valley ducks aged from 5 to 18days and 35 (92.11%) mule ducks aged from 17 to 25days were detected positive for NGPV. In the NGPV-positive ducks, the virus detection rates were 81.97% to 8.20% in heart, liver, spleen, lung, kidney, pancreas, bile, thymus, bursa of Fabricius, and brain. The results indicated that NGPV was prevalent in the duck flocks of East China, whereas classical GPV was not detected in Cherry Valley ducks and mule ducks with SBDS. NGPV has extensive tissue tropism in Cherry Valley duck and mule duck, which could invade both the central and peripheral immune organs and break through the blood-brain barrier of ducks. Copyright © 2017 Elsevier B.V. All rights reserved.

27 CFR 9.36 - McDowell Valley.

Code of Federal Regulations, 2010 CFR

2010-04-01

....” (b) Approved maps. The appropriate map for determining the boundaries of the McDowell Valley... and the ridge line (highest elevation line) between the McDowell Creek Valley and the Dooley Creek Valley. (3) Then southeasterly along the ridge line (highest elevation line) to the intersection of the...

27 CFR 9.36 - McDowell Valley.

Code of Federal Regulations, 2011 CFR

2011-04-01

....” (b) Approved maps. The appropriate map for determining the boundaries of the McDowell Valley... and the ridge line (highest elevation line) between the McDowell Creek Valley and the Dooley Creek Valley. (3) Then southeasterly along the ridge line (highest elevation line) to the intersection of the...

Valley Near Nilus Chaos

NASA Technical Reports Server (NTRS)

2003-01-01

MGS MOC Release No. MOC2-504, 5 October 2003

This August 2003 Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows a valley near Nilus Chaos, around 25.2oN, 80.3oW. The scene has a uniform albedo, indicating that all of the landforms are probably mantled by fine, bright dust. Dark streaks on the valley walls indicate places where recent dust avalanches have occurred. The ripple-like dune features on the valley floor were formed by wind, but today they are inactive and covered with dust. A few craters, created by impacting debris, have formed on the dunes, again attesting to their inactivity in the modern martian environment. The image covers an area 3 km (1.9 mi) wide; it is illuminated by sunlight from the lower left.

27 CFR 9.194 - San Antonio Valley.

Code of Federal Regulations, 2011 CFR

2011-04-01

... significance. (b) Approved Maps. The appropriate maps for determining the boundary of the San Antonio Valley...) Hames Valley, California, 1949, photorevised 1978; (2) Tierra Redonda Mountain, California, 1949... southeast corner of section 14, T23S, R9E, on the Hames Valley map; (2) From the beginning point, proceed...

Morning Transition Tracer Experiments in a Deep Narrow Valley.

NASA Astrophysics Data System (ADS)

Whiteman, C. David

1989-07-01

Three sulfur hexafluoride atmospheric tracer experiments were conducted during the post-sunrise temperature inversion breakup period in the deep, narrow Brush Creek Valley of Colorado. Experiments were conducted under clear, undisturbed weather conditions.A continuous elevated tracer plume was produced along the axis of the valley before sunrise and the behavior of the plume during the inversion breakup period was detected down-valley from the release point using an array of radio-controlled sequential bag samplers, a vertical SF6 profiling system carried on a tethered balloon, two portable gas chromatographs operated on a sidewall of the valley, and a continuous real-time SF6 monitor operated from a research aircraft. Supporting meteorological data came primarily from tethered balloon profilers. The nocturnal elevated plume was carried and diffused in down-valley flows. After sunrise, convective boundary layers grew upward from the sunlit valley surfaces, fumigating the elevated plume onto the valley floor and sidewalls. Upslope flow developed in the growing convective boundary layers, carrying fumigated SF6 up the sidewalls and causing a compensating subsidence over the valley center. High post-sunrise SF6 concentrations were experienced on the northeast-facing sidewall of the northwest-southeast oriented valley as a result of cross-valley flow, which developed due to differential solar heating of the sidewalls. Reversal of the down-valley wind system brought air with lower SF6 concentrations into the lower valley.

The Central Valley Hydrologic Model

NASA Astrophysics Data System (ADS)

Faunt, C.; Belitz, K.; Hanson, R. T.

2009-12-01

Historically, California’s Central Valley has been one of the most productive agricultural regions in the world. The Central Valley also is rapidly becoming an important area for California’s expanding urban population. In response to this competition for water, a number of water-related issues have gained prominence: conjunctive use, artificial recharge, hydrologic implications of land-use change, subsidence, and effects of climate variability. To provide information to stakeholders addressing these issues, the USGS made a detailed assessment of the Central Valley aquifer system that includes the present status of water resources and how these resources have changed over time. The principal product of this assessment is a tool, referred to as the Central Valley Hydrologic Model (CVHM), that simulates surface-water flows, groundwater flows, and land subsidence in response to stresses from human uses and from climate variability throughout the entire Central Valley. The CVHM utilizes MODFLOW combined with a new tool called “Farm Process” to simulate groundwater and surface-water flow, irrigated agriculture, land subsidence, and other key processes in the Central Valley on a monthly basis. This model was discretized horizontally into 20,000 1-mi2 cells and vertically into 10 layers ranging in thickness from 50 feet at the land surface to 750 feet at depth. A texture model constructed by using data from more than 8,500 drillers’ logs was used to estimate hydraulic properties. Unmetered pumpage and surface-water deliveries for 21 water-balance regions were simulated with the Farm Process. Model results indicate that human activities, predominately surface-water deliveries and groundwater pumping for irrigated agriculture, have dramatically influenced the hydrology of the Central Valley. These human activities have increased flow though the aquifer system by about a factor of six compared to pre-development conditions. The simulated hydrology reflects spatial

Rift Valley fever phlebovirus NSs protein core domain structure suggests molecular basis for nuclear filaments

PubMed Central

Miller, Ona K; Potter, Jane A; Vijayakrishnan, Swetha; Bhella, David; Naismith, James H; Elliott, Richard M

2017-01-01

Rift Valley fever phlebovirus (RVFV) is a clinically and economically important pathogen increasingly likely to cause widespread epidemics. RVFV virulence depends on the interferon antagonist non-structural protein (NSs), which remains poorly characterized. We identified a stable core domain of RVFV NSs (residues 83–248), and solved its crystal structure, a novel all-helical fold organized into highly ordered fibrils. A hallmark of RVFV pathology is NSs filament formation in infected cell nuclei. Recombinant virus encoding the NSs core domain induced intranuclear filaments, suggesting it contains all essential determinants for nuclear translocation and filament formation. Mutations of key crystal fibril interface residues in viruses encoding full-length NSs completely abrogated intranuclear filament formation in infected cells. We propose the fibrillar arrangement of the NSs core domain in crystals reveals the molecular basis of assembly of this key virulence factor in cell nuclei. Our findings have important implications for fundamental understanding of RVFV virulence. PMID:28915104

Rift Valley fever phlebovirus NSs protein core domain structure suggests molecular basis for nuclear filaments.

PubMed

Barski, Michal; Brennan, Benjamin; Miller, Ona K; Potter, Jane A; Vijayakrishnan, Swetha; Bhella, David; Naismith, James H; Elliott, Richard M; Schwarz-Linek, Ulrich

2017-09-15

Rift Valley fever phlebovirus (RVFV) is a clinically and economically important pathogen increasingly likely to cause widespread epidemics. RVFV virulence depends on the interferon antagonist non-structural protein (NSs), which remains poorly characterized. We identified a stable core domain of RVFV NSs (residues 83-248), and solved its crystal structure, a novel all-helical fold organized into highly ordered fibrils. A hallmark of RVFV pathology is NSs filament formation in infected cell nuclei. Recombinant virus encoding the NSs core domain induced intranuclear filaments, suggesting it contains all essential determinants for nuclear translocation and filament formation. Mutations of key crystal fibril interface residues in viruses encoding full-length NSs completely abrogated intranuclear filament formation in infected cells. We propose the fibrillar arrangement of the NSs core domain in crystals reveals the molecular basis of assembly of this key virulence factor in cell nuclei. Our findings have important implications for fundamental understanding of RVFV virulence.

NV PFA - Steptoe Valley

DOE Data Explorer

Jim Faulds

2015-10-29

All datasets and products specific to the Steptoe Valley model area. Includes a packed ArcMap project (.mpk), individually zipped shapefiles, and a file geodatabase for the northern Steptoe Valley area; a GeoSoft Oasis montaj project containing GM-SYS 2D gravity profiles along the trace of our seismic reflection lines; a 3D model in EarthVision; spreadsheet of links to published maps; and spreadsheets of well data.

Immunogenicity and efficacy of a chimpanzee adenovirus-vectored Rift Valley fever vaccine in mice.

PubMed

Warimwe, George M; Lorenzo, Gema; Lopez-Gil, Elena; Reyes-Sandoval, Arturo; Cottingham, Matthew G; Spencer, Alexandra J; Collins, Katharine A; Dicks, Matthew D J; Milicic, Anita; Lall, Amar; Furze, Julie; Turner, Alison V; Hill, Adrian V S; Brun, Alejandro; Gilbert, Sarah C

2013-12-05

Rift Valley Fever (RVF) is a viral zoonosis that historically affects livestock production and human health in sub-Saharan Africa, though epizootics have also occurred in the Arabian Peninsula. Whilst an effective live-attenuated vaccine is available for livestock, there is currently no licensed human RVF vaccine. Replication-deficient chimpanzee adenovirus (ChAd) vectors are an ideal platform for development of a human RVF vaccine, given the low prevalence of neutralizing antibodies against them in the human population, and their excellent safety and immunogenicity profile in human clinical trials of vaccines against a wide range of pathogens. Here, in BALB/c mice, we evaluated the immunogenicity and efficacy of a replication-deficient chimpanzee adenovirus vector, ChAdOx1, encoding the RVF virus envelope glycoproteins, Gn and Gc, which are targets of virus neutralizing antibodies. The ChAdOx1-GnGc vaccine was assessed in comparison to a replication-deficient human adenovirus type 5 vector encoding Gn and Gc (HAdV5-GnGc), a strategy previously shown to confer protective immunity against RVF in mice. A single immunization with either of the vaccines conferred protection against RVF virus challenge eight weeks post-immunization. Both vaccines elicited RVF virus neutralizing antibody and a robust CD8+ T cell response. Together the results support further development of RVF vaccines based on replication-deficient adenovirus vectors, with ChAdOx1-GnGc being a potential candidate for use in future human clinical trials.

27 CFR 9.27 - Lime Kiln Valley.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Lime Kiln Valley. 9.27... OF THE TREASURY LIQUORS AMERICAN VITICULTURAL AREAS Approved American Viticultural Areas § 9.27 Lime Kiln Valley. (a) Name. The name of the viticultural area described in this section is “Lime Kiln Valley...

‘Valley Pearl’ table grape

USDA-ARS?s Scientific Manuscript database

‘Valley Pearl’ is an early to mid-season, white seedless table grape (Vitis vinifera L.) suitable for commercial table grape production where V. vinifera can be grown. Significant characteristics of ‘Valley Pearl’ are its high and consistent fruit production on spur pruned vines and large round berr...

Extraction of Martian valley networks from digital topography

NASA Technical Reports Server (NTRS)

Stepinski, T. F.; Collier, M. L.

2004-01-01

We have developed a novel method for delineating valley networks on Mars. The valleys are inferred from digital topography by an autonomous computer algorithm as drainage networks, instead of being manually mapped from images. Individual drainage basins are precisely defined and reconstructed to restore flow continuity disrupted by craters. Drainage networks are extracted from their underlying basins using the contributing area threshold method. We demonstrate that such drainage networks coincide with mapped valley networks verifying that valley networks are indeed drainage systems. Our procedure is capable of delineating and analyzing valley networks with unparalleled speed and consistency. We have applied this method to 28 Noachian locations on Mars exhibiting prominent valley networks. All extracted networks have a planar morphology similar to that of terrestrial river networks. They are characterized by a drainage density of approx.0.1/km, low in comparison to the drainage density of terrestrial river networks. Slopes of "streams" in Martian valley networks decrease downstream at a slower rate than slopes of streams in terrestrial river networks. This analysis, based on a sizable data set of valley networks, reveals that although valley networks have some features pointing to their origin by precipitation-fed runoff erosion, their quantitative characteristics suggest that precipitation intensity and/or longevity of past pluvial climate were inadequate to develop mature drainage basins on Mars.

Dynamics of Katabatic Winds in Colorado' Brush Creek Valley.

NASA Astrophysics Data System (ADS)

Vergeiner, I.; Dreiseitl, E.; Whiteman, C. David

1987-01-01

A method is proposed to evaluate the coupled mass, momentum and thermal energy budget equations for a deep valley under two-dimensional, steady-state flow conditions. The method requires the temperature, down- valley wind and valley width fields to be approximated by simple analytical functions. The vertical velocity field is calculated using the mass continuity equation. Advection terms in the momentum and energy equations are then calculated using finite differences computed on a vertical two-dimensional grid that runs down the valley's axis. The pressure gradient term in the momentum equation is calculated from the temperature field by means of the hydrostatic equation. The friction term is then calculated as a residual in the xmomentum equation, and the diabatic cooling term is calculated as a residual in the thermal energy budget equation.The method is applied to data from an 8-km-long segment of Colorado's; Brush Creek Valley on the night of 30-31 July 1982. Pressure decreased with distance down the peak on horizontal surfaces, with peak horizontal pressure gradients of 0.04 hPa km1. The valley mass budget indicated that subsidence was required in the valley to support calculated mean along-valley mass flux divergence. Peak subsidence rates on the order of 0.10 m s1 were calculated. Subsiding motions in the valley produced negative vertical down-valley momentum fluxes in the upper valley atmosphere, but produced positive down-valley momentum fluxes below the level of the jet. Friction, calculated as a residual in the x momentum equation, was negative, as expected on physical grounds. and attained reasonable quantitative values.The strong subsidence field in the stable valley atmosphere produced subsidence warming that was only partly counteracted by down-valley cold air advection. Strong diabatic cooling was therefore required in order to account for the weak net cooling of the valley atmosphere during the nighttime period when tethered balloon observations

78 FR 77107 - Notice of Availability for Exclusive, Non-Exclusive, or Partially-Exclusive Licensing of an...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-20

... Valley Fever Virus, Ebola Virus, Andes Virus and Vesicular Stomatitis Virus Infectivity, Compositions and...,966, entitled ``Therapeutic Peptides that Inhibit Rift Valley Fever Virus, Ebola Virus, Andes Virus and Vesicular Stomatitis Virus Infectivity, Compositions and Methods,'' filed on December 6, 2012. The...

Fretted Terrain Valley in Coloe Fossae Region

NASA Technical Reports Server (NTRS)

2006-01-01

[figure removed for brevity, see original site] Figure 1 Click on image for larger version

The image in figure 1 shows lineated valley fill in one of a series of enclosed, intersecting troughs known as Coloe (Choloe) Fossae. Lineated valley fill consists of rows of material in valley centers that are parallel to the valley walls. It is probably made of ice-rich material and boulders that are left behind when the ice-rich material sublimates. Very distinct rows can be seen near the south (bottom) wall of the valley. Lineated valley fill is thought to result from mass wasting (downslope movement) of ice-rich material from valley walls towards their centers. It is commonly found in valleys near the crustal dichotomy that separates the two hemispheres of Mars. The valley shown here joins four other valleys with lineated fill near the top left corner of this image. Their juncture is a topographic low, suggesting that the lineated valley fill from the different valleys may be flowing or creeping towards the low area (movement towards the upper left of the image). The valley walls appear smooth at first glance but are seen to be speckled with small craters several meters in diameter at HiRISE resolution (see contrast-enhanced subimage). This indicates that at least some of the wall material has been stable to mass wasting for some period of time. Also seen on the valley wall are elongated features shaped like teardrops. These are most likely slightly older craters that have been degraded due to potentially recent downhill creep. It is unknown whether the valley walls are shedding material today. The subimage is approximately 140 x 400 m (450 x 1280 ft).

Image PSP_001372_2160 was taken by the High Resolution Imaging Science Experiment (HiRISE) camera onboard the Mars Reconnaissance Orbiter spacecraft on November 11, 2006. The complete image is centered at 35.5 degrees latitude, 56.8 degrees East longitude. The range to the target site was 290.3 km (181

Impact of Global Climate on Rift Valley Fever and other Vector-borne Disease Outbreaks

NASA Astrophysics Data System (ADS)

Linthicum, K. J.

2017-12-01

Rift Valley fever is a viral disease of animals and humans in Africa and the Middle East that is transmitted by mosquitoes. Since the virus was first isolated in Kenya in 1930 it has caused significant impact to animal and human health and national economies, and it is of concern to the international agricultural and public health community. In this presentation we will describe the (1) ecology of disease transmission as it relates to climate, (2) the impact of climate and other environmental conditions on outbreaks, (3) the ability to use global climate information to predict outbreaks, (4) effective response activities, and (4) the potential to mitigate globalization.

Victor Valley College Agreement between the Victor Valley Community College District and the Victor Valley College California Teachers Association Chapter 1170. July 1989 - June 1992.

ERIC Educational Resources Information Center

Victor Valley Community Coll. District, Victorville, CA.

The collective bargaining agreement between the Victor Valley College Board of Trustees and the Victor Valley College California Teachers Association/National Education Association is presented. This contract, covering the period from July 1989 through June 1992, deals with the following topics: bargaining agent recognition; district and…

Valley spin polarization of Tl/Si(111)

NASA Astrophysics Data System (ADS)

Stolwijk, Sebastian D.; Schmidt, Anke B.; Sakamoto, Kazuyuki; Krüger, Peter; Donath, Markus

2017-11-01

The metal/semiconductor hybrid system Tl/Si(111)-(1 ×1 ) exhibits a unique Tl-derived surface state with remarkable properties. It lies within the silicon band gap and forms spin-momentum-locked valleys close to the Fermi energy at the K ¯ and K¯' points. These valleys are completely spin polarized with opposite spin orientation at K ¯ and K¯' and show a giant spin splitting of more than 0.5 eV. We present a detailed preparation study of the surface system and demonstrate that the electronic valleys are extremely robust, surviving exposure to 100 L hydrogen and 500 L oxygen. We investigate the influence of additional Tl atoms on the spin-polarized valleys. By combining photoemission and inverse photoemission, we prove the existence of fully spin-polarized valleys crossing the Fermi level. Moreover, these metallic valleys carry opposite Berry curvature at K ¯ and K¯', very similar to WSe2, promising a large spin Hall effect. Thus, Tl/Si(111)-(1 ×1 ) possesses all necessary key properties for spintronic applications.

Electrical valley filtering in transition metal dichalcogenides

NASA Astrophysics Data System (ADS)

Hsieh, Tzu-Chi; Chou, Mei-Yin; Wu, Yu-Shu

2018-03-01

This work investigates the feasibility of electrical valley filtering for holes in transition metal dichalcogenides. We look specifically into the scheme that utilizes a potential barrier to produce valley-dependent tunneling rates, and perform the study with both a k .p -based analytic method and a recursive Green's function-based numerical method. The study yields the transmission coefficient as a function of incident energy and transverse wave vector, for holes going through lateral quantum barriers oriented in either armchair or zigzag directions, in both homogeneous and heterogeneous systems. The main findings are the following: (1) The tunneling current valley polarization increases with increasing barrier width or height; (2) both the valley-orbit interaction and band structure warping contribute to valley-dependent tunneling, with the former contribution being manifest in structures with asymmetric potential barriers, and the latter being orientation dependent and reaching maximum for transmission in the armchair direction; and (3) for transmission ˜0.1 , a tunneling current valley polarization of the order of 10 % can be achieved.

Observation of valley-dependent beams in photonic graphene.

PubMed

Deng, Fusheng; Sun, Yong; Wang, Xiao; Xue, Rui; Li, Yuan; Jiang, Haitao; Shi, Yunlong; Chang, Kai; Chen, Hong

2014-09-22

Valley-dependent propagation of light in an artificial photonic hexagonal lattice, akin to electrons in graphene, is investigated in microwave regime. Both numerical and experimental results show that the valley degeneracy in the photonic graphene is broken when the frequency is away from the Dirac point. The peculiar anisotropic wave transport property due to distinct valleys is analyzed using the equifrequency contours. More interestingly, the valley-dependent self-collimation and beam splitting phenomena are experimentally demonstrated with the armchair and zigzag interfaces, respectively. Our results confirm that there are two inequivalent Dirac points that lead to two distinct valleys in photonic graphene, which could be used to control the flow of light and might be used to carry information in valley polarized beam splitter, collimator or guiding device.

27 CFR 9.58 - Carmel Valley.

Code of Federal Regulations, 2011 CFR

2011-04-01

....” (b) Approved maps. The approved maps for determining the boundary of the Carmel Valley viticultural... Ridge, Calif., dated 1956; and (5) Rana Creek, Calif., dated 1956. (c) Boundary. The Carmel Valley...

27 CFR 9.58 - Carmel Valley.

Code of Federal Regulations, 2010 CFR

2010-04-01

....” (b) Approved maps. The approved maps for determining the boundary of the Carmel Valley viticultural... Ridge, Calif., dated 1956; and (5) Rana Creek, Calif., dated 1956. (c) Boundary. The Carmel Valley...

Water resources of Parowan Valley, Iron County, Utah

USGS Publications Warehouse

Marston, Thomas M.

2017-08-29

Parowan Valley, in Iron County, Utah, covers about 160 square miles west of the Red Cliffs and includes the towns of Parowan, Paragonah, and Summit. The valley is a structural depression formed by northwest-trending faults and is, essentially, a closed surface-water basin although a small part of the valley at the southwestern end drains into the adjacent Cedar Valley. Groundwater occurs in and has been developed mainly from the unconsolidated basin-fill aquifer. Long-term downward trends in groundwater levels have been documented by the U.S. Geological Survey (USGS) since the mid-1950s. The water resources of Parowan Valley were assessed during 2012 to 2014 with an emphasis on refining the understanding of the groundwater and surface-water systems and updating the groundwater budget.Surface-water discharge of five perennial mountain streams that enter Parowan Valley was measured from 2013 to 2014. The total annual surface-water discharge of the five streams during 2013 to 2014 was about 18,000 acre-feet (acre-ft) compared to the average annual streamflow of about 22,000 acre-ft from USGS streamgages operated on the three largest of these streams from the 1940s to the 1980s. The largest stream, Parowan Creek, contributes more than 50 percent of the annual surface-water discharge to the valley, with smaller amounts contributed by Red, Summit, Little, and Cottonwood Creeks.Average annual recharge to the Parowan Valley groundwater system was estimated to be about 25,000 acre-ft from 1994 to 2013. Nearly all recharge occurs as direct infiltration of snowmelt and rainfall on the Markagunt Plateau east of the valley. Smaller amounts of recharge occur as infiltration of streamflow and unconsumed irrigation water near the east side of the valley on alluvial fans associated with mountain streams at the foot of the Red Cliffs. Subsurface flow from the mountain block to the east of the valley is a significant source of groundwater recharge to the basin-fill aquifer

Optical manipulation of valley pseduospin in 2D semiconductors

NASA Astrophysics Data System (ADS)

Ye, Ziliang

Valley polarization associated with the occupancy in the energy degenerate but quantum mechanically distinct valleys in the momentum space closely resembles spin polarization and has been proposed as a pseudospin carrier for future quantum information technologies. Monolayers of transition metal dichalcogenide (TMDC) crystals, with broken inversion symmetry and large spin-orbital coupling, support robust valley polarization and therefore provide an important platform for studying valley-dependent physics. Besides optical excitation and photoluminescence detection, valley polarization has been electrically measured through the valley Hall effect and created through spin injection from ferromagnetic semiconductor contacts. Moreover, the energy degeneracy of the valley degree of freedom has been lifted by the optical Stark effect. Recently, we have demonstrated optical manipulation of valley coherence, i.e., of the valley pseudospin, by the optical Stark effect in monolayer WSe2. Using below-bandgap circularly polarized light, we rotated the valley pseudospin on the femtosecond time scale. Both the direction and speed of the rotation can be optically controlled by tuning the dynamic phase of excitons in opposite valleys. The pseudospin rotation was identified by changes in the polarization of the photoluminescence. In addition, by varying the time delay between the excitation and control pulses, we directly probed the lifetime of the intervalley coherence. Similar rotation levels have also been observed in static magneto-optic experiments. Our work presents an important step towards the full control of the valley degree of freedom in 2D semiconductors. The work was done in collaboration with Dr. Dezheng Sun and Prof. Tony F. Heinz.

[Present status of an arbovirus infection: yellow fever, its natural history of hemorrhagic fever, Rift Valley fever].

PubMed

Digoutte, J P

1999-12-01

. Intermediate yellow fever--a term coined to define epidemia which do not correspond exactly to urban yellow fever. The cycle involves men and monkeys through wild vectors as Aedes furcifer but also through Aedes aegypti and the mortality rate is much lower than for urban epidemics. In urban yellow fever, man is the only vertebrate host involved in the circulation of the virus, the vector being generally Aedes aegypti. This vector maintains a selective pressure, increasing the transmission of virus capable of producing high viremia in man. In the selvatic cycles, two cycles can be distinguished: one of maintenance which does not increase the quantity of virus in circulation and one of amplification which does increase this quantity. As we shall see, it develops into an epizootic form but also in an epidemic form in man. When the decrease in yellow fevers across Africa is considered, it appears that all major epidemics occur in West Africa inspite of the presence of wild cycles of the yellow fever virus in Central and East Africa. For the rare epidemics that have occurred there, the vector has never been Aedes aegypti. In a recent outbreak in Kenya, the vector was Aedes bromeliae. The examination of part of the gene encoding for envelope protein showed the presence of two geographical types corresponding to West-Africa and Central East-Africa. Clinically speaking, yellow fever is an haemorrhagic fever with hepatitis similar to other haemorrhagic fevers such as Rift Valley fever. When, in 1987, an outbreak of haemorrhagic fever occurred in southern Mauritania, for several days it was thought to be yellow fever. Four days later, the diagnosis was corrected by isolating and identifying the virus as that of Rift Valley fever (RVFV). RVFV causes several pathogenic syndromes in human beings: acute febrile illness, haemorrhagic fever, haemorrhagic fever with hepatitis, nervous syndromes or ocular disease. Mortality rate was high for haemorrhagic fever with hepatitis, reaching 36

Origin of the Valley Networks On Mars: A Hydrological Perspective

NASA Technical Reports Server (NTRS)

Gulick, Virginia C.

2000-01-01

The geomorphology of the Martian valley networks is examined from a hydrological perspective for their compatibility with an origin by rainfall, globally higher heat flow, and localized hydrothermal systems. Comparison of morphology and spatial distribution of valleys on geologic surfaces with terrestrial fluvial valleys suggests that most Martian valleys are probably not indicative of a rainfall origin, nor are they indicative of formation by an early global uniformly higher heat flow. In general, valleys are not uniformly distributed within geologic surface units as are terrestrial fluvial valleys. Valleys tend to form either as isolated systems or in clusters on a geologic surface unit leaving large expanses of the unit virtually untouched by erosion. With the exception of fluvial valleys on some volcanoes, most Martian valleys exhibit a sapping morphology and do not appear to have formed along with those that exhibit a runoff morphology. In contrast, terrestrial sapping valleys form from and along with runoff valleys. The isolated or clustered distribution of valleys suggests localized water sources were important in drainage development. Persistent ground-water outflow driven by localized, but vigorous hydrothermal circulation associated with magmatism, volcanism, impacts, or tectonism is, however, consistent with valley morphology and distribution. Snowfall from sublimating ice-covered lakes or seas may have provided an atmospheric water source for the formation of some valleys in regions where the surface is easily eroded and where localized geothermal/hydrothermal activity is sufficient to melt accumulated snowpacks.

EPA Region 1 - Valley Depth in Meters

EPA Pesticide Factsheets

Raster of the Depth in meters of EPA-delimited Valleys in Region 1.Valleys (areas that are lower than their neighbors) were extracted from a Digital Elevation Model (USGS, 30m) by finding the local average elevation, subtracting the actual elevation from the average, and selecting areas where the actual elevation was below the average. The landscape was sampled at seven scales (circles of 1, 2, 4, 7, 11, 16, and 22 km radius) to take into account the diversity of valley shapes and sizes. Areas selected in at least four scales were designated as valleys.

Biologically Informed Individual-Based Network Model for Rift Valley Fever in the US and Evaluation of Mitigation Strategies

PubMed Central

Scoglio, Caterina M.

2016-01-01

Rift Valley fever (RVF) is a zoonotic disease endemic in sub-Saharan Africa with periodic outbreaks in human and animal populations. Mosquitoes are the primary disease vectors; however, Rift Valley fever virus (RVFV) can also spread by direct contact with infected tissues. The transmission cycle is complex, involving humans, livestock, and multiple species of mosquitoes. The epidemiology of RVFV in endemic areas is strongly affected by climatic conditions and environmental variables. In this research, we adapt and use a network-based modeling framework to simulate the transmission of RVFV among hypothetical cattle operations in Kansas, US. Our model considers geo-located livestock populations at the individual level while incorporating the role of mosquito populations and the environment at a coarse resolution. Extensive simulations show the flexibility of our modeling framework when applied to specific scenarios to quantitatively evaluate the efficacy of mosquito control and livestock movement regulations in reducing the extent and intensity of RVF outbreaks in the United States. PMID:27662585

Biologically Informed Individual-Based Network Model for Rift Valley Fever in the US and Evaluation of Mitigation Strategies.

PubMed

Scoglio, Caterina M; Bosca, Claudio; Riad, Mahbubul H; Sahneh, Faryad D; Britch, Seth C; Cohnstaedt, Lee W; Linthicum, Kenneth J

Rift Valley fever (RVF) is a zoonotic disease endemic in sub-Saharan Africa with periodic outbreaks in human and animal populations. Mosquitoes are the primary disease vectors; however, Rift Valley fever virus (RVFV) can also spread by direct contact with infected tissues. The transmission cycle is complex, involving humans, livestock, and multiple species of mosquitoes. The epidemiology of RVFV in endemic areas is strongly affected by climatic conditions and environmental variables. In this research, we adapt and use a network-based modeling framework to simulate the transmission of RVFV among hypothetical cattle operations in Kansas, US. Our model considers geo-located livestock populations at the individual level while incorporating the role of mosquito populations and the environment at a coarse resolution. Extensive simulations show the flexibility of our modeling framework when applied to specific scenarios to quantitatively evaluate the efficacy of mosquito control and livestock movement regulations in reducing the extent and intensity of RVF outbreaks in the United States.

The first imported case of Rift Valley fever in China reveals a genetic reassortment of different viral lineages.

PubMed

Liu, Jingyuan; Sun, Yulan; Shi, Weifeng; Tan, Shuguang; Pan, Yang; Cui, Shujuan; Zhang, Qingchao; Dou, Xiangfeng; Lv, Yanning; Li, Xinyu; Li, Xitai; Chen, Lijuan; Quan, Chuansong; Wang, Qianli; Zhao, Yingze; Lv, Qiang; Hua, Wenhao; Zeng, Hui; Chen, Zhihai; Xiong, Haofeng; Jiang, Chengyu; Pang, Xinghuo; Zhang, Fujie; Liang, Mifang; Wu, Guizhen; Gao, George F; Liu, William J; Li, Ang; Wang, Quanyi

2017-01-18

We report the first imported case of Rift Valley fever (RVF) in China. The patient returned from Angola, a non-epidemic country, with an infection of a new reassortant from different lineages of Rift Valley fever viruses (RVFVs). The patient developed multiorgan dysfunction and gradually recovered with continuous renal replacement therapy and a short regimen of methylprednisolone treatment. The disordered cytokines and chemokines in the plasma of the patient revealed hypercytokinemia, but the levels of protective cytokines were low upon admission and fluctuated as the disease improved. Whole-genome sequencing and phylogenetic analysis revealed that the imported strain was a reassortant comprising the L and M genes from lineage E and the S gene from lineage A. This case highlights that RVFV had undergone genetic reassortment, which could potentially alter its biological properties, cause large outbreaks and pose a serious threat to global public health as well as the livestock breeding industry.

Preliminary hydrogeologic assessment near the boundary of the Antelope Valley and El Mirage Valley groundwater basins, California

USGS Publications Warehouse

Stamos, Christina L.; Christensen, Allen H.; Langenheim, Victoria

2017-07-19

The increasing demands on groundwater for water supply in desert areas in California and the western United States have resulted in the need to better understand groundwater sources, availability, and sustainability. This is true for a 650-square-mile area that encompasses the Antelope Valley, El Mirage Valley, and Upper Mojave River Valley groundwater basins, about 50 miles northeast of Los Angeles, California, in the western part of the Mojave Desert. These basins have been adjudicated to ensure that groundwater rights are allocated according to legal judgments. In an effort to assess if the boundary between the Antelope Valley and El Mirage Valley groundwater basins could be better defined, the U.S. Geological Survey began a cooperative study in 2014 with the Mojave Water Agency to better understand the hydrogeology in the area and investigate potential controls on groundwater flow and availability, including basement topography.Recharge is sporadic and primarily from small ephemeral washes and streams that originate in the San Gabriel Mountains to the south; estimates range from about 400 to 1,940 acre-feet per year. Lateral underflow from adjacent basins has been considered minor in previous studies; underflow from the Antelope Valley to the El Mirage Valley groundwater basin has been estimated to be between 100 and 1,900 acre-feet per year. Groundwater discharge is primarily from pumping, mostly by municipal supply wells. Between October 2013 and September 2014, the municipal pumpage in the Antelope Valley and El Mirage Valley groundwater basins was reported to be about 800 and 2,080 acre-feet, respectively.This study was motivated by the results from a previously completed regional gravity study, which suggested a northeast-trending subsurface basement ridge and saddle approximately 3.5 miles west of the boundary between the Antelope Valley and El Mirage Valley groundwater basins that might influence groundwater flow. To better define potential basement

Serosurveillance of infectious agents in equines of the Central Valley of Costa Rica.

PubMed

Jiménez, D; Romero-Zuñiga, J J; Dolz, G

2014-01-01

Blood samples from 181 equines from the Central Valley of Costa Rica were collected in the year 2012 to determine the presence of antibodies against selected infectious agents in horses and to determine the risk factors associated with these agents. The presence of antibodies against Equine Infectious Anemia Virus (EIAV), Equine Herpes Virus 1 and 4 (EHV-1 and EHV-4), West Nile Virus (WNV), Influenza A Virus (IAV), Equine Viral Arteritis Virus (EVAV), Babesia caballi, Theileria equi, Neospora caninum and Chlamydia abortus was determined using commercial assays, and risk factors associated with seropositivity to the different infectious agents was established. The most seroprevalent agent detected was EHV-4 (96.7%), followed by WNV (44.2%), and IAV (41.8%). Horses >3 years, used for work or sports, and with access to pastures, had significantly increased probability to be seropositive to WNV, whereas horses used for breeding and recreational purposes, being stabled, and without access to pastures, had significantly greater probability to be seropositive to IAV. Seroprevalence to B. caballi (19.9%) was lower than to T. equi (38.1%). For B. caballi, access to pastures was determined as a risk factor, whereas being older than 3 years was established as a risk factor for T. equi. Low seroprevalences were determined for EHV-1 (5.0%), EVAV (5.0%), C. abortus (4.8%), and N. caninum (4.4%). Mares having history of abortion were more likely to be seropositive to EHV-1, whereas horses >3 years, used for work and sports, and mares having multiple parturitions, were more likely to be seropositive to N. caninum. None of the horses were seropositive to EIAV. Earlier, only diseases caused by EIAV, WNV and piroplasmosis were reported in Costa Rica. The present study however, determined the presence of carriers for EHV-1, EHV-4, and EIAV.

Serosurveillance of infectious agents in equines of the Central Valley of Costa Rica

PubMed Central

Jiménez, D.; Romero-Zuñiga, J.J.; Dolz, G.

2014-01-01

Blood samples from 181 equines from the Central Valley of Costa Rica were collected in the year 2012 to determine the presence of antibodies against selected infectious agents in horses and to determine the risk factors associated with these agents. The presence of antibodies against Equine Infectious Anemia Virus (EIAV), Equine Herpes Virus 1 and 4 (EHV-1 and EHV-4), West Nile Virus (WNV), Influenza A Virus (IAV), Equine Viral Arteritis Virus (EVAV), Babesia caballi, Theileria equi, Neospora caninum and Chlamydia abortus was determined using commercial assays, and risk factors associated with seropositivity to the different infectious agents was established. The most seroprevalent agent detected was EHV-4 (96.7%), followed by WNV (44.2%), and IAV (41.8%). Horses >3 years, used for work or sports, and with access to pastures, had significantly increased probability to be seropositive to WNV, whereas horses used for breeding and recreational purposes, being stabled, and without access to pastures, had significantly greater probability to be seropositive to IAV. Seroprevalence to B. caballi (19.9%) was lower than to T. equi (38.1%). For B. caballi, access to pastures was determined as a risk factor, whereas being older than 3 years was established as a risk factor for T. equi. Low seroprevalences were determined for EHV-1 (5.0%), EVAV (5.0%), C. abortus (4.8%), and N. caninum (4.4%). Mares having history of abortion were more likely to be seropositive to EHV-1, whereas horses >3 years, used for work and sports, and mares having multiple parturitions, were more likely to be seropositive to N. caninum. None of the horses were seropositive to EIAV. Earlier, only diseases caused by EIAV, WNV and piroplasmosis were reported in Costa Rica. The present study however, determined the presence of carriers for EHV-1, EHV-4, and EIAV. PMID:26623349

Control of Exciton Valley Coherence in Transition Metal Dichalcogenide Monolayers

NASA Astrophysics Data System (ADS)

Wang, Gang

Current research on Transition Metal Dichalcogenide (TMD) Monolayers is stimulated by their strong light-matter interaction and the possibility to use the valley index in addition to spin as an information carrier. The direct gap interband transitions in TMD monolayers are governed by chiral optical selection rules. Determined by laser helicity, optical transitions in either the K+ or K- valley in momentum space are induced. Very recently the optical generation of valley polarization and valley coherence (coherent superposition of valley states) have been reported. In this work we go a step further by discussing the coherent manipulation of valley states. Linearly polarized laser excitation prepares a coherent superposition of valley states. We demonstrate the control of the exciton valley coherence in monolayer WSe2 by tuning the applied magnetic field perpendicular to the monolayer plane. The induced valley Zeeman splitting between K+ and K- results in a change of the oscillation frequency of the superposition of the valley states, which corresponds to a rotation of the exciton valley pseudo-spin. We show rotation of this coherent superposition of valley states by angles as large as 30 degrees in applied fields up to 9T and discuss valley coherence in other TMD monolayer materials. This exciton valley coherence control on ps time scale could be an important step towards complete control of qubits based on the valley degree of freedom. In collaboration with X. Marie, T. Amand, C. Robert, F. Cadiz, P. Renucci, B. Urbaszek (Université de Toulouse, INSA-CNRS-UPS, LPCNO, France), B. L. Liu (Institute of Physics, Chinese Academy of Sciences, China) and we acknowledge ERC Grant No. 306719.

Geology and water resources of Owens Valley, California

USGS Publications Warehouse

Hollett, Kenneth J.; Danskin, Wesley R.; McCaffrey, William F.; Walti, Caryl L.

1991-01-01

Owens Valley, a long, narrow valley located along the east flank of the Sierra Nevada in east-central California, is the main source of water for the city of Los Angeles. The city diverts most of the surface water in the valley into the Owens River-Los Angeles Aqueduct system, which transports the water more than 200 miles south to areas of distribution and use. Additionally, ground water is pumped or flows from wells to supplement the surface-water diversions to the river-aqueduct system. Pumpage from wells needed to supplement water export has increased since 1970, when a second aqueduct was put into service, and local concerns have been expressed that the increased pumpage may have had a detrimental effect on the environment and the indigenous alkaline scrub and meadow plant communities in the valley. The scrub and meadow communities depend on soil moisture derived from precipitation and the unconfined part of a multilayered aquifer system. This report, which describes the hydrogeology of the aquifer system and the water resources of the valley, is one in a series designed to (1) evaluate the effects that groundwater pumping has on scrub and meadow communities and (2) appraise alternative strategies to mitigate any adverse effects caused by, pumping. Two principal topographic features are the surface expression of the geologic framework--the high, prominent mountains on the east and west sides of the valley and the long, narrow intermountain valley floor. The mountains are composed of sedimentary, granitic, and metamorphic rocks, mantled in part by volcanic rocks as well as by glacial, talus, and fluvial deposits. The valley floor is underlain by valley fill that consists of unconsolidated to moderately consolidated alluvial fan, transition-zone, glacial and talus, and fluvial and lacustrine deposits. The valley fill also includes interlayered recent volcanic flows and pyroclastic rocks. The bedrock surface beneath the valley fill is a narrow, steep-sided graben

Geohydrology of the Unconsolidated Valley-Fill Aquifer in the Meads Creek Valley, Schuyler and Steuben Counties, New York

USGS Publications Warehouse

Miller, Todd S.; Bugliosi, Edward F.; Reddy, James E.

2008-01-01

The Meads Creek valley encompasses 70 square miles of predominantly forested uplands in the upper Susquehanna River drainage basin. The valley, which was listed as a Priority Waterbody by the New York State Department of Environmental Conservation in 2004, is prone to periodic flooding, mostly in its downstream end, where development is occurring most rapidly. Hydraulic characteristics of the unconsolidated valley-fill aquifer were evaluated, and seepage rates in losing and gaining tributaries were calculated or estimated, in an effort to delineate the aquifer geometry and identify the factors that contribute to flooding. Results indicated that (1) Meads Creek gained about 61 cubic feet of flow per second (about 6.0 cubic feet per second per mile of stream channel) from ground-water discharge and inflow from tributaries in its 10.2-mile reach between the northernmost and southernmost measurement sites; (2) major tributaries in the northern part of the valley are not significant sources of recharge to the aquifer; and (3) major tributaries in the central and southern part of the valley provide recharge to the aquifer. The ground-water portion of streamflow in Meads Creek (excluding tributary inflow) was 11.3 cubic feet per second (ft3/s) in the central part of the valley and 17.2 ft3/s in the southern part - a total of 28.5 ft3/s. Ground-water levels were measured in 29 wells finished in unconfined deposits for construction of a potentiometric-surface map to depict directions of ground-water flow within the valley. In general, ground water flows from the edges of the valley toward Meads Creek and ultimately discharges to it. The horizontal hydraulic gradient for the entire 12-mile-long aquifer averages about 30 feet per mile, whereas the gradient in the southern fourth of the valley averages about half that - about 17 feet per mile. A water budget for the aquifer indicated that 28 percent of recharge was derived from precipitation that falls on the aquifer, 32

Mosquito-borne viruses circulating in Kinshasa, Democratic Republic of the Congo.

PubMed

Mbanzulu, Kennedy Makola; Wumba, Roger; Mukendi, Jean-Pierre Kambala; Zanga, Josué Kikana; Shija, Fortunate; Bobanga, Thierry Lengu; Aloni, Michel Ntetani; Misinzo, Gerald

2017-04-01

Diseases caused by mosquito-borne viruses are among the most important emerging diseases that threaten human and animal health, particularly in Africa. However, little attention has been paid to these diseases in the Democratic Republic of the Congo (DRC). The present cross-sectional study was undertaken between March and May 2014 to investigate the presence of mosquito-borne viruses in mosquitoes collected from five municipalities of Kinshasa, DRC. Mosquitoes were collected using BG-Sentinel traps and battery-powered aspirators. Female mosquitoes were pooled according to their genera and sampling locations, preserved in RNAlater, and later screened for viruses using reverse transcription PCR (RT-PCR) assays. A total of 2922 mosquitoes were collected and 29 pools of female mosquitoes, containing approximately 30 mosquitoes each, were tested. Twelve of the 29 (41.4%) mosquito pools were found to be infected with at least one arbovirus, with eight (27.5%) pools positive for Alphavirus, nine (31%) for Flavivirus, and five (17.2%) for Bunyaviridae. Chikungunya, o'nyong'nyong, and Rift valley fever viruses were detected. The present study shows that mosquitoes in Kinshasa carry mosquito-borne viruses that may have serious public health implications. Further investigations on the presence of mosquito-borne viruses in the human and livestock populations of Kinshasa and DRC are recommended. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Observation of valley-selective microwave transport in photonic crystals

NASA Astrophysics Data System (ADS)

Ye, Liping; Yang, Yuting; Hong Hang, Zhi; Qiu, Chunyin; Liu, Zhengyou

2017-12-01

Recently, the discrete valley degree of freedom has attracted extensive attention in condensed matter physics. Here, we present an experimental observation of the intriguing valley transport for microwaves in photonic crystals, including the bulk valley transport and the valley-projected edge modes along the interface separating different photonic insulating phases. For both cases, valley-selective excitations are realized by a point-like chiral source located at proper locations inside the samples. Our results are promising for exploring unprecedented routes to manipulate microwaves.

California's Central Valley Groundwater Study: A Powerful New Tool to Assess Water Resources in California's Central Valley

USGS Publications Warehouse

Faunt, Claudia C.; Hanson, Randall T.; Belitz, Kenneth; Rogers, Laurel

2009-01-01

Competition for water resources is growing throughout California, particularly in the Central Valley. Since 1980, the Central Valley's population has nearly doubled to 3.8 million people. It is expected to increase to 6 million by 2020. Statewide population growth, anticipated reductions in Colorado River water deliveries, drought, and the ecological crisis in the Sacramento-San Joaquin Delta have created an intense demand for water. Tools and information can be used to help manage the Central Valley aquifer system, an important State and national resource.

Experimental West Nile Virus Infection in Rabbits: An Alternative Model for Studying Induction of Disease and Virus Control

PubMed Central

Suen, Willy W.; Uddin, Muhammad J.; Wang, Wenqi; Brown, Vienna; Adney, Danielle R.; Broad, Nicole; Prow, Natalie A.; Bowen, Richard A.; Hall, Roy A.; Bielefeldt-Ohmann, Helle

2015-01-01

The economic impact of non-lethal human and equine West Nile virus (WNV) disease is substantial, since it is the most common presentation of the infection. Experimental infection with virulent WNV strains in the mouse and hamster models frequently results in severe neural infection and moderate to high mortality, both of which are not representative features of most human and equine infections. We have established a rabbit model for investigating pathogenesis and immune response of non-lethal WNV infection. Two species of rabbits, New Zealand White (Oryctolagus cuniculus) and North American cottontail (Sylvilagus sp.), were experimentally infected with virulent WNV and Murray Valley encephalitis virus strains. Infected rabbits exhibited a consistently resistant phenotype, with evidence of low viremia, minimal-absent neural infection, mild-moderate neuropathology, and the lack of mortality, even though productive virus replication occurred in the draining lymph node. The kinetics of anti-WNV neutralizing antibody response was comparable to that commonly seen in infected horses and humans. This may be explained by the early IFNα/β and/or γ response evident in the draining popliteal lymph node. Given this similarity to the human and equine disease, immunocompetent rabbits are, therefore, a valuable animal model for investigating various aspects of non-lethal WNV infections. PMID:26184326

27 CFR 9.90 - Willamette Valley.

Code of Federal Regulations, 2010 CFR

2010-04-01

...) “Roseburg,” Location Diagram NL 10-2, 1958 (revised 1970). (c) Boundaries. The Willamette Valley... valleys of Little River, Mosby Creek, Sharps Creek and Lost Creek to the intersection of R1W/R1E and State...

Valley photonic crystals for control of spin and topology

NASA Astrophysics Data System (ADS)

Dong, Jian-Wen; Chen, Xiao-Dong; Zhu, Hanyu; Wang, Yuan; Zhang, Xiang

2017-03-01

Photonic crystals offer unprecedented opportunity for light manipulation and applications in optical communication and sensing. Exploration of topology in photonic crystals and metamaterials with non-zero gauge field has inspired a number of intriguing optical phenomena such as one-way transport and Weyl points. Recently, a new degree of freedom, valley, has been demonstrated in two-dimensional materials. Here, we propose a concept of valley photonic crystals with electromagnetic duality symmetry but broken inversion symmetry. We observe photonic valley Hall effect originating from valley-dependent spin-split bulk bands, even in topologically trivial photonic crystals. Valley-spin locking behaviour results in selective net spin flow inside bulk valley photonic crystals. We also show the independent control of valley and topology in a single system that has been long pursued in electronic systems, resulting in topologically-protected flat edge states. Valley photonic crystals not only offer a route towards the observation of non-trivial states, but also open the way for device applications in integrated photonics and information processing using spin-dependent transportation.