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Vesicular stomatitis (VS) is a viral disease of horses, cattle and swine caused by vesiculoviruses (VSV) of the Rhabdoviridae family. The disease is a zoonosis. VS is endemic in the Western Hemisphere, where its incidence is confi...
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Vesicular stomatitis (VS) is a viral disease of horses, cattle and swine caused by vesiculoviruses (VSV) of the Rhabdoviridae family. The disease is a zoonosis. VS is endemic in the Western Hemisphere, where its incidence is confined to the warmer regions of North America, as well as Central and South America with tropical climate. The article presents the most important issues concerning the historical background and current status of the disease and its etiological agent. The impact of climatic and ecological conditions on the emergence of new outbreaks and virus strain evolution is discussed, as well as the role of insects in the epidemiology of infections and limited possibilities of specific prevention. The importance of VS virus as a vaccine and oncolytic vector and prospects for its use in the prevention of human infectious diseases and cancer therapy are also highlighted.
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We have used vesicular stomatitis virus (VSV) to determine the cost of antiserum resistance during escape from a polyclonal immune response. Replication of VSV in the presence of polyclonal antiserum resulted in the selection of a...
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We have used vesicular stomatitis virus (VSV) to determine the cost of antiserum resistance during escape from a polyclonal immune response. Replication of VSV in the presence of polyclonal antiserum resulted in the selection of antibody-escape mutants, as shown by increased fitness in the presence of antiserum and by increased resistance to neutralization. However, resistance came at a cost of overall fitness loss in the BHK-21 host cells. Sequencing of the surface G glycoprotein showed that two to four mutations were fixed in each population, most of which mapped in the A1 and A2 antigenic sites. Selected resistant populations were passaged as large populations in BHK-21 cells under constant conditions, which would normally lead to fitness increases. Nevertheless, many of the populations showed little or no sign of recovery, although the resistant phenotype was maintained. These results suggest that while antiserum resistance can develop, it may come at a cost in fitness and further limitations in the adaptability of the populations.
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The nucleoprotein (N) of vesicular stomatitis virus (VSV) plays a central role in transcription and replication by encapsidating genome RNA to form a nucleocapsid as the template for the RNA synthesis. Using minigenome system we e...
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The nucleoprotein (N) of vesicular stomatitis virus (VSV) plays a central role in transcription and replication by encapsidating genome RNA to form a nucleocapsid as the template for the RNA synthesis. Using minigenome system we evaluated the roles of 21 amino acids of the N-terminal arm of N in forming functional N RNA templates and found that three triple-amino-acid substitutions (TVK4-6A3, RII7-9A3, and VIV13-15A3) and one single-amino-acid substitution (R7A) resulted in RNA synthesis loss. But all the mutants maintain the ability to oligomerize N, interact with P, and encapsidate viral RNA for template formation. Further analysis showed that the nucleocapsid formed by these mutants failed to protect RNA from nuclease digestion. Then, we found that only recombinant viruses containing R7A could be recovered. Our results show that the several amino acids within the N-terminal arm of N contribute to the template function beyond its role in RNA encapsidation and viral growth. (C) 2015 Elsevier Inc. All rights reserved.
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Enterovirus 71 (EV71) belonging to the Picornaviridae family is considered the most frequently detected causative agent in hand-foot-and-mouth disease (HFMD) and is a serious threat to public health in the Asia-Pacific region. The...
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Enterovirus 71 (EV71) belonging to the Picornaviridae family is considered the most frequently detected causative agent in hand-foot-and-mouth disease (HFMD) and is a serious threat to public health in the Asia-Pacific region. There are currently no approved vaccines or effective drugs for EV71. In this study, using recombinant vesicular stomatitis virus (rVSV) expressing viral VP1 protein (mVP1) of EV71 as a control, we generated two types of rVSVs that can form EV71 virus-like particles (VLPs). First, we co-infected two rVSVs singly expressing P1 (mP1) and 3CD (m3CD) of EV71. Second, we inserted P1 and 3CD into one VSV backbone to generate an rVSV expressing P1 and 3CD together (mP1-3CD). When P1 and 3CD were expressed in the cells either co-infected with mP1 and m3CD (mP1/m3CD) or infected with mP1-3CD, P1 was cleaved by 3CD and produced VP1, VP3, and VP0 to form VLP5. Furthermore, mice immunized with mP1/m3CD or mP1-3CD showed higher humoral and cellular immunity responses than mice immunized with mVP1. Finally, the rVSVs expressing the EV71 proteins were evaluated in mice to determine their potential to protect against a lethal EV71 virus challenge, and among all the rVSVs, the mP1-3CD was shown to be the most promising vaccine candidate for EV71 protection. (C) 2016 Elsevier Ltd. All rights reserved.
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Self-propagating, infectious, virus-like particles are generated in animal cell lines transfected with a Semliki Forest virus RNA replicon encoding a single viral structural protein, the vesicular stomatitis virus (VSV) glycoprote...
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Self-propagating, infectious, virus-like particles are generated in animal cell lines transfected with a Semliki Forest virus RNA replicon encoding a single viral structural protein, the vesicular stomatitis virus (VSV) glycoprotein. We show here that the
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The RNaselll enzyme Dicer is required for mature microRNA production. Although extensive investigation has been carried out to determine the role of Dicer/miRNAs in the immune system, their function in mature CD8~+ T cells has not...
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The RNaselll enzyme Dicer is required for mature microRNA production. Although extensive investigation has been carried out to determine the role of Dicer/miRNAs in the immune system, their function in mature CD8~+ T cells has not been examined. We deleted Dicer in mature polyclonal and TCR transgenic CD8~+ T cells using either tat-cre or the distal Ick promoter, which drives cre expression after the stage of positive selection. Following anti-genic challenge by a pathogen infection in vivo, Dicer-deleted CD8~+ T cells failed to accumulate at the usual peak of the response. Surprisingly however, we found that deletion of Dicer in mature CD8~+ T cells allowed them to respond more rapidly than control cells to TCR stimuli in vitro. In response to anti-CD3 plus anti-CD28 stimulation, Dicer-deleted T cells up-regulated CD69 faster and entered the first mitosis earlier than control T cells. In addition, activated Dicer~(-/-) cells failed to rapidly down-regulate CD69 when removed from the TCR stimulus. As a probable consequence of this sustained CD69 expression, Dicer~(-/-) T cells showed defective migration out of the central lymphoid organs in vivo. We identify miR-1307301, which are dramatically up-regulated following T-cell activation, as able to down-regulate CD69 expression via binding to a conserved site in the 3'UTR of CD69 mRNA. Thus, cellular functions dependent on Dicer expression are not required for the early steps in CD8~+ T-cell activation, but are essential for their survival and accumulation.
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Chikungunya virus (CHIKV) and Zika virus (ZIKV) have recently expanded their range in the world and caused serious and widespread outbreaks of near pandemic proportions. There are no licensed vaccines that protect against these co...
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Chikungunya virus (CHIKV) and Zika virus (ZIKV) have recently expanded their range in the world and caused serious and widespread outbreaks of near pandemic proportions. There are no licensed vaccines that protect against these co-circulating viruses that are transmitted by invasive mosquito vectors. We report here on the development of a single-dose, bivalent experimental vaccine for CHIKV and ZIKV. This vaccine is based on a chimeric vesicular stomatitis virus (VSV) that expresses the CHIKV envelope polyprotein (E3-E2-6K-E1) in place of the VSV glycoprotein (G) and also expresses the membrane-envelope (ME) glycoproteins of ZIKV. This vaccine induced neutralizing antibody responses to both CHIKV and ZIKV in wild-type mice and in interferon receptor-deficient A129 mice, animal models for CHIKV and ZIKV infection. A single vaccination of A129 mice with the vector protected these mice against infection with both CHIKV and ZIKV. Our single-dose vaccine could provide durable, low-cost protection against both CHIKV and ZIKV for people traveling to or living in areas where both viruses are circulating, which include most tropical regions in the world. (C) 2018 Elsevier Ltd. All rights reserved.
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From September 2014 to April 2015, 6 persons who had occupational exposures to Zaire ebolavirus in West Africa received investigational agent rVSV-ZEBOV or TKM-100802 for postexposure prophylaxis and were monitored in the United S...
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From September 2014 to April 2015, 6 persons who had occupational exposures to Zaire ebolavirus in West Africa received investigational agent rVSV-ZEBOV or TKM-100802 for postexposure prophylaxis and were monitored in the United States. All patients experienced self-limited symptoms after postexposure prophylaxis; none developed Ebola virus disease.
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Selected mutant strains of vesicular stomatitis virus (VSV) are described that are unable to combat endogenous IFN-beta signaling within infected normal cells and as a result are dramatically more selective for productive growth i...
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Selected mutant strains of vesicular stomatitis virus (VSV) are described that are unable to combat endogenous IFN-beta signaling within infected normal cells and as a result are dramatically more selective for productive growth in tumor cells having a defective antiviral response. The VSV mutants may have the potential to be used clinically as a systemic oncolytic agent for the treatment of distal and metastatic cancers.
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Decline in CD4 T cell immune responses is associated with aging. Although a number of immunological defects have been identified in elderly mice (>18 months old), a key early-onset immune defect at middle age could be a driver or ...
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Decline in CD4 T cell immune responses is associated with aging. Although a number of immunological defects have been identified in elderly mice (>18 months old), a key early-onset immune defect at middle age could be a driver or contributor to defective CD4 T cell responses. Our studies demonstrate that age-related alterations in DC subsets within the priming environment of middle-aged mice (12 months old) correlate with and can directly contribute to decreases in antigen-specific CD4 T cell Th1 differentiation, which measured by T-bet and IFN-γ expression, was decreased significantly in T cells following VSV infection or s.c. immunization with a protein antigen in the context of immune stimulation via OX40. The deficient Th1 phenotype, observed following protein antigen challenge, was found to be the result of an age-related decrease in an inflammatory DC subset (CD11b+ Gr-1/Ly6C+) in the dLN that corresponded with T cell dysfunction. In the virus model, we observed significant changes in two DC subsets: mDCs and pDCs. Thus, different, early age-related changes in the DC profile in the priming environment can significantly contribute to impaired Th1 differentiation, depending on the type of immunological challenge.
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