A5040289752- Influenza Virus Research Studies
- interferon and immune responses
- Immune Response and Inflammation
- Respiratory viral infections research
- Animal Disease Management and Epidemiology
- Viral Infections and Vectors
- Mosquito-borne diseases and control
- Viral gastroenteritis research and epidemiology
- HIV Research and Treatment
- RNA modifications and cancer
- Systemic Lupus Erythematosus Research
- Monoclonal and Polyclonal Antibodies Research
- Immunotherapy and Immune Responses
- Cytokine Signaling Pathways and Interactions
- Renal Diseases and Glomerulopathies
- Chronic Lymphocytic Leukemia Research
- RNA Research and Splicing
- T-cell and B-cell Immunology
- Travel-related health issues
- Respiratory Support and Mechanisms
- RNA and protein synthesis mechanisms
- Herpesvirus Infections and Treatments
- Immune Cell Function and Interaction
- Diabetes and associated disorders
Takeda (United States)
2020
Visterra (United States)
2015-2019
Washington University in St. Louis
2008-2016
Centers for Disease Control and Prevention
2006-2013
National Center for Immunization and Respiratory Diseases
2007-2013
Emory University
2006-2009
National Influenza Center
2005-2006
The spread of highly pathogenic avian influenza H5N1 viruses across Asia in 2003 and 2004 devastated domestic poultry populations resulted the largest most lethal virus outbreak humans to date. To better understand potential isolated during this epizootic event cause disease mammals, we used mouse ferret models evaluate relative virulence selected representing multiple genetic geographical groups compared them earlier strains from humans. Four five human isolates tested were for both mice...
ABSTRACT Highly pathogenic avian H5N1 influenza viruses are now widespread in poultry Asia and have recently spread to some African European countries. Interspecies transmission of these humans poses a major threat public health. To better understand the basis pathogenesis viruses, we investigated role proinflammatory cytokines transgenic mice deficient interleukin-6 (IL-6), macrophage inflammatory protein 1 alpha (MIP-1α), IL-1 receptor (IL-1R), or tumor necrosis factor (TNFR1) by use two A...
Influenza viruses are negative-sense, single-stranded, enveloped RNA belonging to the family Orthomyxoviridae. Three types exist, influenza A, B, and C. All infect humans, but only A B major human pathogens. type divided into subtypes based on genetic antigenic differences in two surface spike proteins, hemagglutinin (HA) neuraminidase (NA). The appropriate cell lines be used for isolation of or depend clinical information host origin. MDCK cells preferred line from specimens.
Mice carrying a wild-type Mx1 gene (Mx1+/+) differ from standard laboratory mice (Mx1-/-) in being highly resistant to infection with common strains of influenza A virus. We report that also protects against the pandemic human 1918 virus and lethal H5N1 strain Vietnam. Resistance Mx1+/+ but not Mx1-/- was enhanced if animals were treated single dose exogenous alpha interferon before infection. Thus, interferon-induced resistance factor represents key component murine innate immune system...
Prior studies have shown that 2′-O methyltransferase activity of flaviviruses, coronaviruses, and poxviruses promotes viral evasion Ifit1, an interferon-stimulated innate immune effector protein. Viruses lacking exhibited attenuation in primary macrophages was rescued cells Ifit1 gene expression. Here, we examined the role restricting pathogenesis vivo wild type WNV (WNV-WT) a mutant NS5 (WNV-E218A) methylation 5′ RNA cap. While deletion had marginal effects on WNV-WT pathogenesis, WNV-E218A...
Sterile alpha and HEAT/Armadillo motif (SARM) is a highly conserved Toll/interleukin-1 receptor (TIR)-containing adaptor protein that believed to negatively regulate signaling of the pathogen recognition receptors Toll-like 3 (TLR3) TLR4. To test its physiological function in context microbial infection, we generated SARM(-/-) mice evaluated impact this deficiency on pathogenesis West Nile virus (WNV), neurotropic flavivirus requires TLR restrict infection. Although SARM was preferentially...
Type I interferon (IFN) signaling coordinates an early antiviral program in infected and uninfected cells by inducing IFN-stimulated genes (ISGs) that modulate viral entry, replication, assembly. However, the specific functions vivo of most ISGs remain unknown. Here, we examined contribution ISG viperin to control West Nile virus (WNV) genetically deficient mice. While modest increases levels WNV replication were observed for primary viperin(-/-) macrophages dendritic cells, no appreciable...
Periodic outbreaks of highly pathogenic avian H5N1 influenza viruses and the current H1N1 pandemic highlight need for a more detailed understanding virus pathogenesis. To investigate host transcriptional response induced by viruses, we used functional-genomics approach to compare gene expression profiles in lungs from 129S6/SvEv mice infected with either fully reconstructed 1918 (1918) or Vietnam/1203/04 (VN/1203). Although reached similar titers lung caused lethal infections, mean time...
Interferon regulatory factors (IRF)-3 and IRF-7 are master transcriptional that regulate type I IFN gene (IFN-α/β) induction innate immune defenses after virus infection. Prior studies in mice with single deletions of the IRF-3 or genes showed increased vulnerability to West Nile (WNV) Whereas cells lacking reduced IFN-α levels WNV infection, those had relatively normal IFN-b production. Here, we generated IRF-3−/−× IRF-7−/− double knockout (DKO) mice, analyzed pathogenesis, responses,...
Increasing resistance to currently available influenza antivirals highlights the need develop alternate approaches for prevention and/or treatment of influenza. DAS181 (Fludase), a novel sialidase fusion protein that enzymatically removes sialic acids on respiratory epithelium, exhibits potent antiviral activity against A and B viruses. Here, we use mouse model evaluate efficacy highly pathogenic avian H5N1 virus. When used treat mice daily beginning 1 day before infection with...
Type I interferons (IFN-α/β) control viral infection by triggering the expression of genes that restrict transcription, translation, replication, and assembly. Many viruses induce IFN responses after recognition cytoplasmic or endosomal RNA sensors (RIG-I-like helicases [RLR] Toll-like receptors [TLR]), which signal through cognate adaptor signaling molecules IPS-1, TRIF, MyD88. Recent studies have demonstrated IPS-1-dependent induction IFN-α/β downstream RLR restricts West Nile virus (WNV)...
Highly pathogenic avian influenza viruses of the H5N1 subtype continue to cross species barrier infect humans and cause severe disease. It has been suggested that an exaggerated immune response contributes pathogenesis virus infection in mammals. In particular, infections are associated with a high expression proinflammatory cytokines, including interleukin-1 (IL-1) tumor necrosis factor alpha (TNF-α).We investigated compounding affects both cytokines on outcome disease by using triple...
Widespread distribution of highly pathogenic avian H5N1 influenza viruses in domesticated and wild birds continues to pose a threat public health, as interspecies transmission virus has resulted increasing numbers human disease cases. Although the mechanism(s) not been fully elucidated, it suggested that ability evade host innate responses, such type I interferon response, may contribute virulence these mammals. We investigated role interferons (alpha/beta [IFN-alpha/beta]) might play...
ABSTRACT Although highly pathogenic avian influenza H5N1 viruses have yet to acquire the ability transmit efficiently among humans, increasing genetic diversity these and continued outbreaks in species underscore need for more effective measures control prevention of human virus infection. Additional small animal models with which therapeutic approaches against virulent can be evaluated are needed. In this study, we used guinea pig model evaluate relative virulence selected A viruses. We...
Significance Emerging influenza subtypes, such as the recently identified H7N9 strains, are of considerable public health concern. Although vaccines an important countermeasure, tend to be subtype- and strain-specific, that they may not widely available in event human adaptation spread unanticipated strain or subtype. Additionally, strains have demonstrated ability develop resistance existing antivirals, including oseltamivir. As such, there is a need for novel interventions can treat and/or...
Seasonal influenza is a major public health concern in vulnerable populations. Here we investigated the safety, tolerability, and pharmacokinetics of broadly neutralizing monoclonal antibody (VIS410) against Influenza A Phase 1 clinical trial. Based on these results preclinical data, implemented mathematical modeling approach to investigate whether VIS410 could be used prophylactically lessen burden seasonal epidemic protect at-risk groups from associated complications.Using single-ascending...