A5067937189- Influenza Virus Research Studies
- Respiratory viral infections research
- Animal Disease Management and Epidemiology
- Immune Response and Inflammation
- Viral gastroenteritis research and epidemiology
- Viral Infections and Vectors
- Receptor Mechanisms and Signaling
- interferon and immune responses
- RNA and protein synthesis mechanisms
- Protein Structure and Dynamics
- Virology and Viral Diseases
- Viral Infections and Immunology Research
- Animal Virus Infections Studies
- Viral Infections and Outbreaks Research
- Monoclonal and Polyclonal Antibodies Research
- Pneumonia and Respiratory Infections
- X-ray Diffraction in Crystallography
- Travel-related health issues
- Virus-based gene therapy research
- SARS-CoV-2 and COVID-19 Research
- Crystallization and Solubility Studies
- Immune Cell Function and Interaction
- Hepatitis C virus research
- Neuroendocrine regulation and behavior
- COVID-19 epidemiological studies
St. Jude Children's Research Hospital
2016-2025
D.I. Ivanovsky Institute of Virology Russian Academy of Medical Sciences
1997-2007
University of Tennessee at Knoxville
2006-2007
Office of Infectious Diseases
2006
Shantou University
2006
Shantou University Medical College
2006
University of Hong Kong
2006
National Institute Of Hygiene And Epidemiology
2006
Ministry of Agriculture and Rural Development
2005-2006
National Institute of Veterinary Research
2005-2006
Wild waterfowl, including ducks, are natural hosts of influenza A viruses. These viruses rarely caused disease in ducks until 2002, when some H5N1 strains became highly pathogenic. Here we show that these reverting to nonpathogenicity ducks. Ducks experimentally infected with isolated between 2003 and 2004 shed virus for an extended time (up 17 days), during which variant low pathogenicity were selected. results suggest the duck has become “Trojan horse” Asian The unaffected by infection...
Wild waterfowl are the natural reservoir of all influenza A viruses, and these viruses usually nonpathogenic in birds. However, since late 2002, H5N1 outbreaks Asia have resulted mortality among recreational parks, domestic flocks, wild migratory The evolutionary stasis between virus its host may been disrupted, prompting us to ask whether resistant disease they can still act as a for viruses. To better understand biology ducks attempt answer this question, we inoculated juvenile mallards...
ABSTRACT Several novel anti-influenza compounds are in various phases of clinical development. One these, T-705 (favipiravir), has a mechanism action that is not fully understood but suggested to target influenza virus RNA-dependent RNA polymerase. We investigated the activity against A (H1N1) viruses by applying selective drug pressure over multiple sequential passages MDCK cells. found treatment did select specific mutations potential proteins, including PB1, PB2, PA, and NP. Phenotypic...
H5N1 influenza viruses transmitted from poultry to humans in Asia cause high mortality and pose a pandemic threat. Viral genes important for cell tropism replication efficiency must be identified elucidate target virulence factors. We applied reverse genetics generate reassortants combining of lethal A/Vietnam/1203/04 (VN1203), fatal human case isolate, nonlethal A/chicken/Vietnam/C58/04 (CH58) tested their pathogenicity ferrets mice. The viruses' hemagglutinins have six amino acids...
Highly pathogenic avian influenza A(H5N1) viruses of clade 2.3.4.4b underwent an explosive geographic expansion in 2021 among wild birds and domestic poultry across Asia, Europe, Africa. By the end 2021, were detected North America, signifying further intercontinental spread. Here we show that western movement was quickly followed by reassortment with circulating resulting acquisition different combinations ribonucleoprotein genes. These reassortant are genotypically phenotypically diverse,...
Abstract Since late 2021, highly pathogenic avian influenza (HPAI) viruses of A/goose/Guangdong/1/1996 (H5N1) lineage have caused widespread mortality in wild birds and poultry the United States. Concomitant with spread HPAI are increasing numbers mammalian infections, including captive mesocarnivores carnivores central nervous system involvement. Here we report HPAI, A(H5N1) clade 2.3.4.4b, a common bottlenose dolphin ( Tursiops truncatus ) from Florida, Pathological findings include...
ABSTRACT The 2004 outbreaks of H5N1 influenza viruses in Vietnam and Thailand were highly lethal to humans poultry; therefore, newly emerging avian A pose a continued threat, not only species but also humans. We studied the pathogenicity four human nine H5N1/04 ferrets (an excellent model for studies). All isolates fatal intranasally inoculated ferrets. isolate A/Vietnam/1203/04 (H5N1) was most pathogenic isolate; severity disease associated with broad tissue tropism high virus titers...
Mutations of the conserved residues influenza virus neuraminidase (NA) that are associated with NA inhibitor (NAI) resistance decrease sialidase activity and/or stability NA, thus compromising viral fitness. In fact, clinically derived NAI-resistant variants different mutations have shown transmissibilities in ferrets (M. L. Herlocher, R. Truscon, S. Elias, H. Yen, N. A. Roberts, E. Ohmit, and Monto, J. Infect. Dis. 190:1627-1630, 2004). Molecular characterization mutant viruses a...
ABSTRACT The orally administered neuraminidase (NA) inhibitor RWJ-270201 was tested in parallel with zanamivir and oseltamivir against a panel of avian influenza viruses for inhibition NA activity replication tissue culture. agents were then protection mice lethal H5N1 H9N2 virus infection. In vitro, highly effective all nine subtypes. by (50% inhibitory concentration, 0.9 to 4.3 nM) superior that carboxylate. inhibited the both Eurasian American lineages MDCK cells 0.5 11.8 μM). Mice given...
ABSTRACT The H5N1 influenza virus, which killed humans and poultry in 1997, was a reassortant that possibly arose one type of domestic present the live-poultry markets Hong Kong. Given all precursors H5N1/97 are still circulating southern China, reassortment event generated could be repeated. Because A/goose/Guangdong/1/96-like (H5N1; Go/Gd) viruses proposed donors hemagglutinin gene we investigated continued circulation, host range, transmissibility Go/Gd-like poultry. caused weight loss...
ABSTRACT Neuraminidase inhibitors (NAIs) are antivirals designed to target conserved residues at the neuraminidase (NA) enzyme active site in influenza A and B viruses. The that interact with NAIs under selective pressure, but only a few have been linked resistance. In A/Wuhan/359/95 (H3N2) recombinant virus background, we characterized seven charged, NA (R118, R371, E227, R152, R224, E276, D151) directly not reported confer resistance NAIs. These were replaced amino acids possess side...
We mapped the hemagglutinin (HA) antigenic epitopes of a highly pathogenic H5N1 influenza virus on three-dimensional HA structure by characterizing escape mutants recombinant containing A/Vietnam/1203/04 (H5N1) deltaHA and neuraminidase genes in genetic background A/Puerto Rico/8/34 (H1N1) virus. The were selected with panel eight anti-HA monoclonal antibodies (MAbs), seven to one A/Chicken/Pennsylvania/8125/83 (H5N2) virus, mutants' sequenced. amino acid changes suggested three MAb groups:...
Control of highly pathogenic avian H5N1 influenza viruses is a major public-health concern. Antiviral drugs could be the only option early in pandemic.METHODS. BALB/c mice were given oseltamivir (0.1, 1, or 10 mg/kg/day) twice daily by oral gavage; first dose was 4 h before inoculation with A/Vietnam/1203/04 (VN1203/04) virus. Five- and 8-day regimens evaluated.RESULTS. Oseltamivir produced dose-dependent antiviral effect against VN1203/04 vivo (P<.01). The 5-day regimen at mg/kg/day...
Effective antiviral drugs are essential for early control of an influenza pandemic. It is therefore crucial to evaluate the possible threat posed by neuraminidase (NA) inhibitor-resistant viruses with pandemic potential. Four NA mutations (E119G, H274Y, R292K, and N294S) that have been reported confer resistance inhibitors were each introduced into recombinant A/Vietnam/1203/04 (VN1203) H5N1 virus. For comparison, same A/Puerto Rico/8/34 (PR8) H1N1 The E119G R292K significantly compromised...
ABSTRACT Highly pathogenic H5N1 influenza viruses have infected an increasing number of humans in Asia, with high mortality rates and the emergence multiple distinguishable clades. It is not known whether antiviral drugs that are effective against contemporary human will be systemically replicating viruses, such as these pathogens. Therefore, we evaluated use neuraminidase (NA) inhibitor oseltamivir for early postexposure prophylaxis treatment ferrets exposed to representatives two clades...
The abilities to infect and transmit efficiently among humans are essential for a novel influenza A virus cause pandemic. To evaluate the pandemic potential of widely disseminated H5N1 viruses, ferret contact model using experimental groups comprised one inoculated two ferrets was used study transmissibility four human viruses isolated from 2003 2006. effects viral pathogenicity receptor binding specificity (affinity synthetic sialosaccharides with alpha2,3 or alpha2,6 linkages) on were...
While the molecular mechanism of membrane fusion by influenza virus hemagglutinin (HA) protein has been studied extensively in vitro, role acid-dependent HA activation replication, pathogenesis, and transmission vivo not characterized. To investigate biological significance pH protein, we compared properties four recombinant viruses with altered acid stability to those wild-type A/chicken/Vietnam/C58/04 (H5N1) vitro mallards. Membrane was activated at 5.9. Wild-type had a calculated...