Robert G. Webster

Isolation of Highly Pathogenic Avian Influenza H5N1 Virus from Saker Falcons (Falco cherrug) in the Middle East (2009)

Henju Marjuki, Ulrich Wernery, Hui-Ling Yen, John Franks, Patrick Seiler, David Walker, ...

There is accumulating evidence that birds of prey are susceptible to fatal infection with highly pathogenic avian influenza (HPAI) virus. We studied the antigenic, molecular, phylogenetic, and...

Influenza virus RNA in the lung and lymphoid tissue of immunologically intact and CD4-depleted mice (2008)

Maryna C. Eichelberger, Maoliang Wang, T William Allan, Robert G. Webster, Peter C. Doherty

The distribution and clearance of viral RNA (vRNA) and mRNA has been analysed for the acute and recovery stages of the pneumonia induced by intranasal infection of C57BL/6J mice with H3N2 influenza A...

CK2beta gene silencing increases cell susceptibility to influenza A virus infection resulting in accelerated virus entry and higher viral protein content (2008)

Marjuki, Henju, Scholtissek, Christoph, Yen, Hui-Ling, Webster, Robert G

Abstract Background Influenza A virus (IVA) exploits diverse cellular gene products to support its replication in the host. The significance of the regulatory (β) subunit of casein kinase 2 (CK2β)...

Higher polymerase activity of a human influenza virus enhances activation of the hemagglutinin-induced Raf/MEK/ERK signal cascade (2007)

Marjuki, Henju, Yen, Hui-Ling, Franks, John, Webster, Robert G, Pleschka, Stephan, Hoffmann, Erich

Abstract Influenza viruses replicate within the nucleus of infected cells. Viral genomic RNA, three polymerase subunits (PB2, PB1, and PA), and the nucleoprotein (NP) form ribonucleoprotein complexes...

Influenza in Migratory Birds and Evidence of Limited Intercontinental Virus Exchange (2007)

Scott Krauss, Caroline A. Obert, John Franks, David Walker, Kelly Jones, Patrick Seiler, ...

Migratory waterfowl of the world are the natural reservoirs of influenza viruses of all known subtypes. However, it is unknown whether these waterfowl perpetuate highly pathogenic (HP) H5 and H7...

Y.: H5N1 outbreaks and enzootic influenza (2006)

Robert G. Webster, Malik Peiris, Honglin Chen, Yi Guan

Ongoing outbreaks of H5N1 avian influenza in migratory waterfowl, domestic poultry, and humans in Asia during the summer of 2005 present a continuing, protean pandemic threat. We review the zoonotic...

Molecular Basis for the Generation in Pigs of Influenza A Viruses with Pandemic Potential (1998)

Ito, Toshihiro, Kelm, Sørge, Baum, Linda G., Krauss, Scott, Castrucci, Maria R., ...

Genetic and biologic observations suggest that pigs may serve as "mixing vessels" for the generation of human-avian influenza A virus reassortants, similar to those responsible for the 1957 and 1968...

Molecular Basis for the Generation in Pigs of Influenza A Viruses with Pandemic Potential (1998)

Ito, Toshihiro, Kelm, Sørge, Baum, Linda G., Krauss, Scott, Castrucci, Maria R., ...

Genetic and biologic observations suggest that pigs may serve as "mixing vessels" for the generation of human-avian influenza A virus reassortants, similar to those responsible for the 1957 and 1968...

DNA immunization for influenza virus: studies using hemagglutinin- and nucleoprotein-expressing DNAs (1997)

Robinson, Harriet L., Boyle, Christine Margaret, Feltquate, David Marc, Morin, Merribeth J., Santoro, Joseph C., Webster, Robert G.

DNA-based immunizations have been used to analyze the ability of DNA-expressed hemagglutinin (HA) and nucleoprotein (NP) to protect BALB/c mice against a homologous influenza virus, A/PR/8/34 (H1N1),...

Different T helper cell types and antibody isotypes generated by saline and gene gun DNA immunization (1997)

Feltquate, David Marc, Heaney, Shaun, Webster, Robert G., Robinson, Harriet L.

Several routes and methods of DNA immunization have been shown to generate Ab, Th cells, and CTL responses. However, few studies have directly compared the immune responses generated by different...

Role of different lymphoid tissues in the initiation and maintenance of DNA-raised antibody responses to the influenza virus H1 glycoprotein (1996)

Boyle, Christine Margaret, Morin, Merribeth J., Webster, Robert G., Robinson, Harriet L.

Antibody responses in mice immunized by a single gene gun inoculation of plasmid expressing the influenza virus H1 hemagglutinin and in mice immunized by a sublethal H1 influenza virus infection have...

Subtype cross-reactive, infection-enhancing antibody responses to influenza A viruses (1994)

Tamura, Manabu, Webster, Robert G., Ennis, Francis A.

Antibody-dependent enhancement of the uptake of influenza A virus by Fc receptor-bearing cells was analyzed by using virus strains of the three human influenza A virus subtypes, A/PR/8/34 (H1N1),...

DNA vaccines: protective immunizations by parenteral, mucosal, and gene-gun inoculations (1993)

Fynan, Ellen F., Webster, Robert G., Fuller, D H, Haynes, Joel R., Santoro, Joseph C., Robinson, Harriet L.

Plasmid DNAs expressing influenza virus hemagglutinin glycoproteins have been tested for their ability to raise protective immunity against lethal influenza challenges of the same subtype. In trials...

Interspecies Transmission and Reassortment of Influenza A Viruses in Pigs and Turkeys in the United States (1992)

Wright, Stephen M., Kawaoka, Yoshihiro, Sharp, Gerold B., Senne, Dennis A., Webster, Robert G.

Genetic reassortrnent between influenza A viruses in humans and in animals and birds has been implicated in the appearance of new pandemics of human influenza. To determine whether such reassortment...

Molecular characterization of H9N2 influenza viruses: Were they the donors of the “internal” genes of H5N1 viruses in Hong Kong?

Guan, Yi, Shortridge, Kennedy F., Krauss, Scott, Webster, Robert G.

The origin of the H5N1 influenza viruses that killed six of eighteen infected humans in 1997 and were highly pathogenic in chickens has not been resolved. These H5N1 viruses transmitted directly to...

A DNA transfection system for generation of influenza A virus from eight plasmids

Hoffmann, Erich, Neumann, Gabriele, Kawaoka, Yoshihiro, Hobom, Gerd, Webster, Robert G.

We have developed an eight-plasmid DNA transfection system for the rescue of infectious influenza A virus from cloned cDNA. In this plasmid-based expression system, viral cDNA is inserted between the...

Efficacy of Zanamivir against Avian Influenza A Viruses That Possess Genes Encoding H5N1 Internal Proteins and Are Pathogenic in Mammals

Leneva, Irina A., Goloubeva, Olga, Fenton, Robert J., Tisdale, Margaret, Webster, Robert G.

In 1997, an avian H5N1 influenza virus, A/Hong Kong/156/97 (A/HK/156/97), caused six deaths in Hong Kong, and in 1999, an avian H9N2 influenza virus infected two children in Hong Kong. These viruses...

Comparison of Efficacies of RWJ-270201, Zanamivir, and Oseltamivir against H5N1, H9N2, and Other Avian Influenza Viruses

Govorkova, Elena A., Leneva, Irina A., Goloubeva, Olga G., Bush, Karen, Webster, Robert G.

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 of NA activity and...

Comparison of the Activities of Zanamivir, Oseltamivir, and RWJ-270201 against Clinical Isolates of Influenza Virus and Neuraminidase Inhibitor-Resistant Variants

Gubareva, Larisa V., Webster, Robert G., Hayden, Frederick G.

RWJ-270201 is a novel cyclopentane inhibitor of influenza A and B virus neuraminidases (NAs). We compared the ability of RWJ-270201 to inhibit NA activity of clinical influenza isolates and viruses...

Protection against a Lethal Avian Influenza A Virus in a Mammalian System

Riberdy, Janice M., Flynn, Kirsten J., Stech, Juergen, Webster, Robert G., Altman, John D., Doherty, Peter C.

The question of how best to protect the human population against a potential influenza pandemic has been raised by the recent outbreak caused by an avian H5N1 virus in Hong Kong. The likely strategy...

Rapid Evolution of H5N1 Influenza Viruses in Chickens in Hong Kong

Zhou, Nan Nan, Shortridge, Kennedy F., Claas, Eric C. J., Krauss, Scott L., Webster, Robert G.

The H5N1 avian influenza virus that killed 6 of 18 persons infected in Hong Kong in 1997 was transmitted directly from poultry to humans. Viral isolates from this outbreak may provide molecular clues...

Reassortment and Insertion-Deletion Are Strategies for the Evolution of Influenza B Viruses in Nature

McCullers, Jonathan A., Wang, George C., He, Shiqin, Webster, Robert G.

The evolution of influenza B viruses is poorly understood. Reassortment of influenza B viruses in nature as a means of genetic variation has not been considered to be a major contributor to their...

DNA Vaccine Encoding Hemagglutinin Provides Protective Immunity against H5N1 Influenza Virus Infection in Mice

Kodihalli, Shantha, Goto, Hideo, Kobasa, Darwyn L., Krauss, Scott, Kawaoka, Yoshihiro, Webster, Robert G.

In Hong Kong in 1997, a highly lethal H5N1 avian influenza virus was apparently transmitted directly from chickens to humans with no intermediate mammalian host and caused 18 confirmed infections and...

Molecular Basis for the Generation in Pigs of Influenza A Viruses with Pandemic Potential

Ito, Toshihiro, Kelm, Sørge, Baum, Linda G., Krauss, Scott, Castrucci, Maria R., ...

Genetic and biologic observations suggest that pigs may serve as “mixing vessels” for the generation of human-avian influenza A virus reassortants, similar to those responsible for the 1957 and...

Characterization of the Influenza A Virus Gene Pool in Avian Species in Southern China: Was H6N1 a Derivative or a Precursor of H5N1?

Hoffmann, Erich, Stech, Juergen, Leneva, Irina, Krauss, Scott, Scholtissek, Christoph, Chin, Po San, ...

In 1997, an H5N1 influenza virus outbreak occurred in chickens in Hong Kong, and the virus was transmitted directly to humans. Because there is limited information about the avian influenza virus...

Genetic Reassortment of Avian, Swine, and Human Influenza A Viruses in American Pigs

Zhou, Nan Nan, Senne, Dennis A., Landgraf, John S., Swenson, Sabrina L., Erickson, Gene, Rossow, Kurt, ...

In late summer through early winter of 1998, there were several outbreaks of respiratory disease in the swine herds of North Carolina, Texas, Minnesota, and Iowa. Four viral isolates from outbreaks...

Characterization of a Porcine Lung Epithelial Cell Line Suitable for Influenza Virus Studies

Seo, Sang Heui, Goloubeva, Olga, Webby, Richard, Webster, Robert G.

We established a porcine lung epithelial cell line designated St. Jude porcine lung cells (SJPL) and demonstrated that all tested influenza A and B viruses replicated in this cell line. The...

Cross-Reactive, Cell-Mediated Immunity and Protection of Chickens from Lethal H5N1 Influenza Virus Infection in Hong Kong Poultry Markets

Seo, Sang Heui, Webster, Robert G.

In 1997, avian H5N1 influenza virus transmitted from chickens to humans resulted in 18 confirmed infections. Despite harboring lethal H5N1 influenza viruses, most chickens in the Hong Kong poultry...

Evolution of Swine H3N2 Influenza Viruses in the United States

Webby, Richard J., Swenson, Sabrina L., Krauss, Scott L., Gerrish, Philip J., Goyal, Sagar M., Webster, Robert G.

During 1998, severe outbreaks of influenza were observed in four swine herds in the United States. This event was unique because the causative agents, H3N2 influenza viruses, are infrequently...

Rescue of influenza B virus from eight plasmids

Hoffmann, Erich, Mahmood, Kutubuddin, Yang, Chin-Fen, Webster, Robert G., Greenberg, Harry B., Kemble, George

Influenza B virus causes a significant amount of morbidity and mortality, yet the systems to produce high yield inactivated vaccines for these viruses have lagged behind the development of those for...

Characterization of H5N1 Influenza Viruses That Continue To Circulate in Geese in Southeastern China

Webster, Robert G., Guan, Yi, Peiris, Malik, Walker, David, Krauss, Scott, Zhou, Nan Nan, ...

The H5N1 influenza virus, which killed humans and poultry in 1997, was a reassortant that possibly arose in one type of domestic poultry present in the live-poultry markets of Hong Kong. Given that...

Tumor Necrosis Factor Alpha Exerts Powerful Anti-Influenza Virus Effects in Lung Epithelial Cells

Seo, Sang Heui, Webster, Robert G.

Previous studies have associated influenza virus-induced expression of inflammatory cytokines, including tumor necrosis factor alpha (TNF-α), with influenza pathogenesis in the human respiratory...

Cooperation between the Hemagglutinin of Avian Viruses and the Matrix Protein of Human Influenza A Viruses

Scholtissek, Christoph, Stech, Jürgen, Krauss, Scott, Webster, Robert G.

To analyze the compatibility of avian influenza A virus hemagglutinins (HAs) and human influenza A virus matrix (M) proteins M1 and M2, we doubly infected Madin-Darby canine kidney cells with...

Protective Cross-Reactive Cellular Immunity to Lethal A/Goose/Guangdong/1/96-Like H5N1 Influenza Virus Is Correlated with the Proportion of Pulmonary CD8+ T Cells Expressing Gamma Interferon

Seo, Sang Heui, Peiris, Malik, Webster, Robert G.

A/Goose/Guangdong/1/96-like H5N1 influenza viruses now circulating in southeastern China differ genetically from the H5N1 viruses transmitted to humans in 1997 but were their precursors. Here we show...

Neurovirulence in Mice of H5N1 Influenza Virus Genotypes Isolated from Hong Kong Poultry in 2001

Lipatov, Aleksandr S., Krauss, Scott, Guan, Yi, Peiris, Malik, Rehg, Jerold E., Perez, Daniel R., ...

We studied the pathogenicity of five different genotypes (A to E) of highly pathogenic avian H5N1 viruses, which contained HA genes similar to those of the H5N1 virus A/goose/Guangdong/1/96 and five...

Role of Quail in the Interspecies Transmission of H9 Influenza A Viruses: Molecular Changes on HA That Correspond to Adaptation from Ducks to Chickens

Perez, Daniel R., Lim, Wilina, Seiler, Jon P., Yi, Guan, Peiris, Malik, Shortridge, Kennedy F., ...

H9 influenza viruses have become endemic in land-based domestic poultry in Asia and have sporadically crossed to pigs and humans. To understand the molecular determinants of their adaptation to...

Pathogenic and Antigenic Properties of Phylogenetically Distinct Reassortant H3N2 Swine Influenza Viruses Cocirculating in the United States

Richt, Jürgen A., Lager, Kelly M., Janke, Bruce H., Woods, Roger D., Webster, Robert G., Webby, Richard J.

Swine influenza is an acute respiratory disease caused by type A influenza viruses. Before 1998, swine influenza virus isolates in the United States were mainly of the classical H1N1 lineage. Since...

Protection and compensation in the influenza virus-specific CD8+ T cell response

Webby, Richard J., Andreansky, Samita, Stambas, John, Rehg, Jerold E., Webster, Robert G., Doherty, Peter C., ...

Influenza virus-specific CD8+ T cells generally recognize peptides derived from conserved, internal proteins that are not subject to antibody-mediated selection pressure. Prior exposure to any one...

Structural Differences among Hemagglutinins of Influenza A Virus Subtypes Are Reflected in Their Antigenic Architecture: Analysis of H9 Escape Mutants

Kaverin, Nikolai V., Rudneva, Irina A., Ilyushina, Natalia A., Lipatov, Aleksandr S., Krauss, Scott, Webster, Robert G.

We used a panel of monoclonal antibodies to H9 hemagglutinin to select 18 escape mutants of mouse-adapted influenza A/Swine/Hong Kong/9/98 (H9N2) virus. Cross-reactions of the mutants with the...

Virulence of Avian Influenza A Viruses for Squirrel Monkeys

Murphy, Brian R., Hinshaw, Virginia S., Sly, D. Lewis, London, William T., Hosier, Nanette T., Wood, Frank T., ...

Ten serologically distinct avian influenza A viruses were administered to squirrel monkeys and hamsters to compare their replication and virulence with those of human influenza A virus,...

Failure to Detect Hemagglutination-Inhibiting Antibodies with Intact Avian Influenza Virions

Lu, Bao-Lan, Webster, Robert G., Hinshaw, Virginia S.

Avian influenza viruses replicate in a variety of mammals and birds, yet hemagglutination inhibition tests show that postinfection sera from these animals (e.g., ferrets and ducks) have insignificant...

Generation of High-Yielding Influenza A Viruses in African Green Monkey Kidney (Vero) Cells by Reverse Genetics

Ozaki, Hiroichi, Govorkova, Elena A., Li, Chenghong, Xiong, Xiaoping, Webster, Robert G., Webby, Richard J.

Influenza A viruses are the cause of annual epidemics of human disease with occasional outbreaks of pandemic proportions. The zoonotic nature of the disease and the vast viral reservoirs in the...

Reemerging H5N1 Influenza Viruses in Hong Kong in 2002 Are Highly Pathogenic to Ducks

Sturm-Ramirez, Katharine M., Ellis, Trevor, Bousfield, Barry, Bissett, Lucy, Dyrting, Kitman, Rehg, Jerold E., ...

Waterfowl are the natural reservoir of all influenza A viruses, which are usually nonpathogenic in wild aquatic birds. However, in late 2002, outbreaks of highly pathogenic H5N1 influenza virus...

Matrix Gene of Influenza A Viruses Isolated from Wild Aquatic Birds: Ecology and Emergence of Influenza A Viruses

Widjaja, Linda, Krauss, Scott L., Webby, Richard J., Xie, Tao, Webster, Robert G.

Wild aquatic birds are the primary reservoir of influenza A viruses, but little is known about the viruses' gene pool in wild birds. Therefore, we investigated the ecology and emergence of influenza...

Molecular Determinants within the Surface Proteins Involved in the Pathogenicity of H5N1 Influenza Viruses in Chickens

Hulse, Diane J., Webster, Robert G., Russell, Rupert J., Perez, Daniel R.

Although it is established that the cleavage site and glycosylation patterns in the hemagglutinin (HA) play important roles in determining the pathogenicity of H5 avian influenza viruses, some...

Neuraminidase Inhibitor-Rimantadine Combinations Exert Additive and Synergistic Anti-Influenza Virus Effects in MDCK Cells

Govorkova, Elena A., Fang, Hong-Bin, Tan, Ming, Webster, Robert G.

There is insufficient information about combination therapy with approved anti-influenza agents. We tested combinations that paired a neuraminidase (NA) inhibitor (zanamivir, oseltamivir carboxylate,...

Lethality to Ferrets of H5N1 Influenza Viruses Isolated from Humans and Poultry in 2004

Govorkova, Elena A., Rehg, Jerold E., Krauss, Scott, Yen, Hui-Ling, Guan, Yi, Peiris, Malik, ...

The 2004 outbreaks of H5N1 influenza viruses in Vietnam and Thailand were highly lethal to humans and to poultry; therefore, newly emerging avian influenza A viruses pose a continued threat, not only...

Studies of H5N1 Influenza Virus Infection of Pigs by Using Viruses Isolated in Vietnam and Thailand in 2004

Choi, Young Ki, Nguyen, Tien Dzung, Ozaki, Hiroichi, Webby, Richard J., Puthavathana, Pilaipan, Buranathal, Chantanee, ...

To determine whether avian H5N1 influenza viruses associated with human infections in Vietnam had transmitted to pigs, we investigated serologic evidence of exposure to H5N1 influenza virus in...

Role of specific hemagglutinin amino acids in the immunogenicity and protection of H5N1 influenza virus vaccines

Hoffmann, Erich, Lipatov, Aleksandr S., Webby, Richard J., Govorkova, Elena A., Webster, Robert G.

If H5N1 influenza viruses become transmissible among humans, vaccination will offer the most effective option to limit their spread. Two human vaccine candidates recently generated by reverse...

Molecular Basis of Replication of Duck H5N1 Influenza Viruses in a Mammalian Mouse Model

Li, Zejun, Chen, Hualan, Jiao, Peirong, Deng, Guohua, Tian, Guobin, Li, Yanbing, ...

We recently analyzed a series of H5N1 viruses isolated from healthy ducks in southern China since 1999 and found that these viruses had progressively acquired the ability to replicate and cause...

Neuraminidase Inhibitor-Resistant Influenza Viruses May Differ Substantially in Fitness and Transmissibility

Yen, Hui-Ling, Herlocher, Louise M., Hoffmann, Erich, Matrosovich, Mikhail N., Monto, Arnold S., Webster, Robert G., ...

Mutations of the conserved residues of influenza virus neuraminidase (NA) that are associated with NA inhibitor (NAI) resistance decrease the sialidase activity and/or stability of the NA, thus...

Human Infection with an Avian H9N2 Influenza A Virus in Hong Kong in 2003

Butt, K. M., Smith, Gavin J. D., Chen, Honglin, Zhang, L. J., Leung, Y. H. Connie, Xu, K. M., ...

Avian H9N2 influenza A virus has caused repeated human infections in Asia since 1998. Here we report that an H9N2 influenza virus infected a 5-year-old child in Hong Kong in 2003. To identify the...

Comparison of the Replication of Influenza A Viruses in Chinese Ring-Necked Pheasants and Chukar Partridges

Humberd, Jennifer, Guan, Yi, Webster, Robert G.

We investigated the replication and transmission of avian influenza A viruses in two species thought to be intermediate hosts in the spread of influenza A viruses in live poultry markets: Chinese...

Detection of Influenza Viruses Resistant to Neuraminidase Inhibitors in Global Surveillance during the First 3 Years of Their Use

Monto, Arnold S., McKimm-Breschkin, Jennifer L., Macken, Catherine, Hampson, Alan W., Hay, Alan, Klimov, Alexander, ...

Emergence of influenza viruses with reduced susceptibility to neuraminidase inhibitors (NAIs) develops at a low level following drug treatment, and person-to-person transmission of resistant virus...

Molecular characterization of H9N2 influenza viruses: Were they the donors of the “internal” genes of H5N1 viruses in Hong Kong?

Guan, Yi, Shortridge, Kennedy F., Krauss, Scott, Webster, Robert G.

The origin of the H5N1 influenza viruses that killed six of eighteen infected humans in 1997 and were highly pathogenic in chickens has not been resolved. These H5N1 viruses transmitted directly to...

A DNA transfection system for generation of influenza A virus from eight plasmids

Hoffmann, Erich, Neumann, Gabriele, Kawaoka, Yoshihiro, Hobom, Gerd, Webster, Robert G.

We have developed an eight-plasmid DNA transfection system for the rescue of infectious influenza A virus from cloned cDNA. In this plasmid-based expression system, viral cDNA is inserted between the...

Efficacy of Zanamivir against Avian Influenza A Viruses That Possess Genes Encoding H5N1 Internal Proteins and Are Pathogenic in Mammals

Leneva, Irina A., Goloubeva, Olga, Fenton, Robert J., Tisdale, Margaret, Webster, Robert G.

In 1997, an avian H5N1 influenza virus, A/Hong Kong/156/97 (A/HK/156/97), caused six deaths in Hong Kong, and in 1999, an avian H9N2 influenza virus infected two children in Hong Kong. These viruses...

Comparison of Efficacies of RWJ-270201, Zanamivir, and Oseltamivir against H5N1, H9N2, and Other Avian Influenza Viruses

Govorkova, Elena A., Leneva, Irina A., Goloubeva, Olga G., Bush, Karen, Webster, Robert G.

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 of NA activity and...

Comparison of the Activities of Zanamivir, Oseltamivir, and RWJ-270201 against Clinical Isolates of Influenza Virus and Neuraminidase Inhibitor-Resistant Variants

Gubareva, Larisa V., Webster, Robert G., Hayden, Frederick G.

RWJ-270201 is a novel cyclopentane inhibitor of influenza A and B virus neuraminidases (NAs). We compared the ability of RWJ-270201 to inhibit NA activity of clinical influenza isolates and viruses...

Protection against a Lethal Avian Influenza A Virus in a Mammalian System

Riberdy, Janice M., Flynn, Kirsten J., Stech, Juergen, Webster, Robert G., Altman, John D., Doherty, Peter C.

The question of how best to protect the human population against a potential influenza pandemic has been raised by the recent outbreak caused by an avian H5N1 virus in Hong Kong. The likely strategy...

Rapid Evolution of H5N1 Influenza Viruses in Chickens in Hong Kong

Zhou, Nan Nan, Shortridge, Kennedy F., Claas, Eric C. J., Krauss, Scott L., Webster, Robert G.

The H5N1 avian influenza virus that killed 6 of 18 persons infected in Hong Kong in 1997 was transmitted directly from poultry to humans. Viral isolates from this outbreak may provide molecular clues...

Reassortment and Insertion-Deletion Are Strategies for the Evolution of Influenza B Viruses in Nature

McCullers, Jonathan A., Wang, George C., He, Shiqin, Webster, Robert G.

The evolution of influenza B viruses is poorly understood. Reassortment of influenza B viruses in nature as a means of genetic variation has not been considered to be a major contributor to their...

DNA Vaccine Encoding Hemagglutinin Provides Protective Immunity against H5N1 Influenza Virus Infection in Mice

Kodihalli, Shantha, Goto, Hideo, Kobasa, Darwyn L., Krauss, Scott, Kawaoka, Yoshihiro, Webster, Robert G.

In Hong Kong in 1997, a highly lethal H5N1 avian influenza virus was apparently transmitted directly from chickens to humans with no intermediate mammalian host and caused 18 confirmed infections and...

Molecular Basis for the Generation in Pigs of Influenza A Viruses with Pandemic Potential

Ito, Toshihiro, Kelm, Sørge, Baum, Linda G., Krauss, Scott, Castrucci, Maria R., ...

Genetic and biologic observations suggest that pigs may serve as “mixing vessels” for the generation of human-avian influenza A virus reassortants, similar to those responsible for the 1957 and...

Characterization of the Influenza A Virus Gene Pool in Avian Species in Southern China: Was H6N1 a Derivative or a Precursor of H5N1?

Hoffmann, Erich, Stech, Juergen, Leneva, Irina, Krauss, Scott, Scholtissek, Christoph, Chin, Po San, ...

In 1997, an H5N1 influenza virus outbreak occurred in chickens in Hong Kong, and the virus was transmitted directly to humans. Because there is limited information about the avian influenza virus...

Genetic Reassortment of Avian, Swine, and Human Influenza A Viruses in American Pigs

Zhou, Nan Nan, Senne, Dennis A., Landgraf, John S., Swenson, Sabrina L., Erickson, Gene, Rossow, Kurt, ...

In late summer through early winter of 1998, there were several outbreaks of respiratory disease in the swine herds of North Carolina, Texas, Minnesota, and Iowa. Four viral isolates from outbreaks...

Characterization of a Porcine Lung Epithelial Cell Line Suitable for Influenza Virus Studies

Seo, Sang Heui, Goloubeva, Olga, Webby, Richard, Webster, Robert G.

We established a porcine lung epithelial cell line designated St. Jude porcine lung cells (SJPL) and demonstrated that all tested influenza A and B viruses replicated in this cell line. The...

Cross-Reactive, Cell-Mediated Immunity and Protection of Chickens from Lethal H5N1 Influenza Virus Infection in Hong Kong Poultry Markets

Seo, Sang Heui, Webster, Robert G.

In 1997, avian H5N1 influenza virus transmitted from chickens to humans resulted in 18 confirmed infections. Despite harboring lethal H5N1 influenza viruses, most chickens in the Hong Kong poultry...

Evolution of Swine H3N2 Influenza Viruses in the United States

Webby, Richard J., Swenson, Sabrina L., Krauss, Scott L., Gerrish, Philip J., Goyal, Sagar M., Webster, Robert G.

During 1998, severe outbreaks of influenza were observed in four swine herds in the United States. This event was unique because the causative agents, H3N2 influenza viruses, are infrequently...

Rescue of influenza B virus from eight plasmids

Hoffmann, Erich, Mahmood, Kutubuddin, Yang, Chin-Fen, Webster, Robert G., Greenberg, Harry B., Kemble, George

Influenza B virus causes a significant amount of morbidity and mortality, yet the systems to produce high yield inactivated vaccines for these viruses have lagged behind the development of those for...

Characterization of H5N1 Influenza Viruses That Continue To Circulate in Geese in Southeastern China

Webster, Robert G., Guan, Yi, Peiris, Malik, Walker, David, Krauss, Scott, Zhou, Nan Nan, ...

The H5N1 influenza virus, which killed humans and poultry in 1997, was a reassortant that possibly arose in one type of domestic poultry present in the live-poultry markets of Hong Kong. Given that...

Tumor Necrosis Factor Alpha Exerts Powerful Anti-Influenza Virus Effects in Lung Epithelial Cells

Seo, Sang Heui, Webster, Robert G.

Previous studies have associated influenza virus-induced expression of inflammatory cytokines, including tumor necrosis factor alpha (TNF-α), with influenza pathogenesis in the human respiratory...

Cooperation between the Hemagglutinin of Avian Viruses and the Matrix Protein of Human Influenza A Viruses

Scholtissek, Christoph, Stech, Jürgen, Krauss, Scott, Webster, Robert G.

To analyze the compatibility of avian influenza A virus hemagglutinins (HAs) and human influenza A virus matrix (M) proteins M1 and M2, we doubly infected Madin-Darby canine kidney cells with...

Protective Cross-Reactive Cellular Immunity to Lethal A/Goose/Guangdong/1/96-Like H5N1 Influenza Virus Is Correlated with the Proportion of Pulmonary CD8+ T Cells Expressing Gamma Interferon

Seo, Sang Heui, Peiris, Malik, Webster, Robert G.

A/Goose/Guangdong/1/96-like H5N1 influenza viruses now circulating in southeastern China differ genetically from the H5N1 viruses transmitted to humans in 1997 but were their precursors. Here we show...

Neurovirulence in Mice of H5N1 Influenza Virus Genotypes Isolated from Hong Kong Poultry in 2001

Lipatov, Aleksandr S., Krauss, Scott, Guan, Yi, Peiris, Malik, Rehg, Jerold E., Perez, Daniel R., ...

We studied the pathogenicity of five different genotypes (A to E) of highly pathogenic avian H5N1 viruses, which contained HA genes similar to those of the H5N1 virus A/goose/Guangdong/1/96 and five...

Role of Quail in the Interspecies Transmission of H9 Influenza A Viruses: Molecular Changes on HA That Correspond to Adaptation from Ducks to Chickens

Perez, Daniel R., Lim, Wilina, Seiler, Jon P., Yi, Guan, Peiris, Malik, Shortridge, Kennedy F., ...

H9 influenza viruses have become endemic in land-based domestic poultry in Asia and have sporadically crossed to pigs and humans. To understand the molecular determinants of their adaptation to...

Pathogenic and Antigenic Properties of Phylogenetically Distinct Reassortant H3N2 Swine Influenza Viruses Cocirculating in the United States

Richt, Jürgen A., Lager, Kelly M., Janke, Bruce H., Woods, Roger D., Webster, Robert G., Webby, Richard J.

Swine influenza is an acute respiratory disease caused by type A influenza viruses. Before 1998, swine influenza virus isolates in the United States were mainly of the classical H1N1 lineage. Since...

Protection and compensation in the influenza virus-specific CD8+ T cell response

Webby, Richard J., Andreansky, Samita, Stambas, John, Rehg, Jerold E., Webster, Robert G., Doherty, Peter C., ...

Influenza virus-specific CD8+ T cells generally recognize peptides derived from conserved, internal proteins that are not subject to antibody-mediated selection pressure. Prior exposure to any one...

Structural Differences among Hemagglutinins of Influenza A Virus Subtypes Are Reflected in Their Antigenic Architecture: Analysis of H9 Escape Mutants

Kaverin, Nikolai V., Rudneva, Irina A., Ilyushina, Natalia A., Lipatov, Aleksandr S., Krauss, Scott, Webster, Robert G.

We used a panel of monoclonal antibodies to H9 hemagglutinin to select 18 escape mutants of mouse-adapted influenza A/Swine/Hong Kong/9/98 (H9N2) virus. Cross-reactions of the mutants with the...

Virulence of Avian Influenza A Viruses for Squirrel Monkeys

Murphy, Brian R., Hinshaw, Virginia S., Sly, D. Lewis, London, William T., Hosier, Nanette T., Wood, Frank T., ...

Ten serologically distinct avian influenza A viruses were administered to squirrel monkeys and hamsters to compare their replication and virulence with those of human influenza A virus,...

Failure to Detect Hemagglutination-Inhibiting Antibodies with Intact Avian Influenza Virions

Lu, Bao-Lan, Webster, Robert G., Hinshaw, Virginia S.

Avian influenza viruses replicate in a variety of mammals and birds, yet hemagglutination inhibition tests show that postinfection sera from these animals (e.g., ferrets and ducks) have insignificant...

Generation of High-Yielding Influenza A Viruses in African Green Monkey Kidney (Vero) Cells by Reverse Genetics

Ozaki, Hiroichi, Govorkova, Elena A., Li, Chenghong, Xiong, Xiaoping, Webster, Robert G., Webby, Richard J.

Influenza A viruses are the cause of annual epidemics of human disease with occasional outbreaks of pandemic proportions. The zoonotic nature of the disease and the vast viral reservoirs in the...

Reemerging H5N1 Influenza Viruses in Hong Kong in 2002 Are Highly Pathogenic to Ducks

Sturm-Ramirez, Katharine M., Ellis, Trevor, Bousfield, Barry, Bissett, Lucy, Dyrting, Kitman, Rehg, Jerold E., ...

Waterfowl are the natural reservoir of all influenza A viruses, which are usually nonpathogenic in wild aquatic birds. However, in late 2002, outbreaks of highly pathogenic H5N1 influenza virus...

Matrix Gene of Influenza A Viruses Isolated from Wild Aquatic Birds: Ecology and Emergence of Influenza A Viruses

Widjaja, Linda, Krauss, Scott L., Webby, Richard J., Xie, Tao, Webster, Robert G.

Wild aquatic birds are the primary reservoir of influenza A viruses, but little is known about the viruses' gene pool in wild birds. Therefore, we investigated the ecology and emergence of influenza...

Molecular Determinants within the Surface Proteins Involved in the Pathogenicity of H5N1 Influenza Viruses in Chickens

Hulse, Diane J., Webster, Robert G., Russell, Rupert J., Perez, Daniel R.

Although it is established that the cleavage site and glycosylation patterns in the hemagglutinin (HA) play important roles in determining the pathogenicity of H5 avian influenza viruses, some...

Neuraminidase Inhibitor-Rimantadine Combinations Exert Additive and Synergistic Anti-Influenza Virus Effects in MDCK Cells

Govorkova, Elena A., Fang, Hong-Bin, Tan, Ming, Webster, Robert G.

There is insufficient information about combination therapy with approved anti-influenza agents. We tested combinations that paired a neuraminidase (NA) inhibitor (zanamivir, oseltamivir carboxylate,...

Lethality to Ferrets of H5N1 Influenza Viruses Isolated from Humans and Poultry in 2004

Govorkova, Elena A., Rehg, Jerold E., Krauss, Scott, Yen, Hui-Ling, Guan, Yi, Peiris, Malik, ...

The 2004 outbreaks of H5N1 influenza viruses in Vietnam and Thailand were highly lethal to humans and to poultry; therefore, newly emerging avian influenza A viruses pose a continued threat, not only...

Studies of H5N1 Influenza Virus Infection of Pigs by Using Viruses Isolated in Vietnam and Thailand in 2004

Choi, Young Ki, Nguyen, Tien Dzung, Ozaki, Hiroichi, Webby, Richard J., Puthavathana, Pilaipan, Buranathal, Chantanee, ...

To determine whether avian H5N1 influenza viruses associated with human infections in Vietnam had transmitted to pigs, we investigated serologic evidence of exposure to H5N1 influenza virus in...

Role of specific hemagglutinin amino acids in the immunogenicity and protection of H5N1 influenza virus vaccines

Hoffmann, Erich, Lipatov, Aleksandr S., Webby, Richard J., Govorkova, Elena A., Webster, Robert G.

If H5N1 influenza viruses become transmissible among humans, vaccination will offer the most effective option to limit their spread. Two human vaccine candidates recently generated by reverse...

Molecular Basis of Replication of Duck H5N1 Influenza Viruses in a Mammalian Mouse Model

Li, Zejun, Chen, Hualan, Jiao, Peirong, Deng, Guohua, Tian, Guobin, Li, Yanbing, ...

We recently analyzed a series of H5N1 viruses isolated from healthy ducks in southern China since 1999 and found that these viruses had progressively acquired the ability to replicate and cause...

Neuraminidase Inhibitor-Resistant Influenza Viruses May Differ Substantially in Fitness and Transmissibility

Yen, Hui-Ling, Herlocher, Louise M., Hoffmann, Erich, Matrosovich, Mikhail N., Monto, Arnold S., Webster, Robert G., ...

Mutations of the conserved residues of influenza virus neuraminidase (NA) that are associated with NA inhibitor (NAI) resistance decrease the sialidase activity and/or stability of the NA, thus...

Human Infection with an Avian H9N2 Influenza A Virus in Hong Kong in 2003

Butt, K. M., Smith, Gavin J. D., Chen, Honglin, Zhang, L. J., Leung, Y. H. Connie, Xu, K. M., ...

Avian H9N2 influenza A virus has caused repeated human infections in Asia since 1998. Here we report that an H9N2 influenza virus infected a 5-year-old child in Hong Kong in 2003. To identify the...

Comparison of the Replication of Influenza A Viruses in Chinese Ring-Necked Pheasants and Chukar Partridges

Humberd, Jennifer, Guan, Yi, Webster, Robert G.

We investigated the replication and transmission of avian influenza A viruses in two species thought to be intermediate hosts in the spread of influenza A viruses in live poultry markets: Chinese...

Detection of Influenza Viruses Resistant to Neuraminidase Inhibitors in Global Surveillance during the First 3 Years of Their Use

Monto, Arnold S., McKimm-Breschkin, Jennifer L., Macken, Catherine, Hampson, Alan W., Hay, Alan, Klimov, Alexander, ...

Emergence of influenza viruses with reduced susceptibility to neuraminidase inhibitors (NAIs) develops at a low level following drug treatment, and person-to-person transmission of resistant virus...

Importance of Neuraminidase Active-Site Residues to the Neuraminidase Inhibitor Resistance of Influenza Viruses

Yen, Hui-Ling, Hoffmann, Erich, Taylor, Garry, Scholtissek, Christoph, Monto, Arnold S., Webster, Robert G., ...

Neuraminidase inhibitors (NAIs) are antivirals designed to target conserved residues at the neuraminidase (NA) enzyme active site in influenza A and B viruses. The conserved residues that interact...

Efficacy of Oseltamivir Therapy in Ferrets Inoculated with Different Clades of H5N1 Influenza Virus▿

Govorkova, Elena A., Ilyushina, Natalia A., Boltz, David A., Douglas, Alan, Yilmaz, Neziha, Webster, Robert G.

Highly pathogenic H5N1 influenza viruses have infected an increasing number of humans in Asia, with high mortality rates and the emergence of multiple distinguishable clades. It is not known whether...

Emergence of Influenza A Virus Variants after Prolonged Shedding from Pheasants▿

Humberd, Jennifer, Boyd, Kelli, Webster, Robert G.

We previously demonstrated the susceptibility of pheasants to infection with influenza A viruses of 15 hemagglutinin (HA) subtypes: 13/23 viruses tested were isolated for ≥14 days, all in the...

Inefficient Transmission of H5N1 Influenza Viruses in a Ferret Contact Model▿

Yen, Hui-Ling, Lipatov, Aleksandr S., Ilyushina, Natalia A., Govorkova, Elena A., Franks, John, Yilmaz, Neziha, ...

The abilities to infect and transmit efficiently among humans are essential for a novel influenza A virus to cause a pandemic. To evaluate the pandemic potential of widely disseminated H5N1 influenza...

Influenza in Migratory Birds and Evidence of Limited Intercontinental Virus Exchange

Krauss, Scott, Obert, Caroline A, Franks, John, Walker, David, Jones, Kelly, Seiler, Patrick, ...

Migratory waterfowl of the world are the natural reservoirs of influenza viruses of all known subtypes. However, it is unknown whether these waterfowl perpetuate highly pathogenic (HP) H5 and H7...

Inhibition of the cytokine response does not protect against lethal H5N1 influenza infection

Salomon, Rachelle, Hoffmann, Erich, Webster, Robert G.

Because proinflammatory cytokines are markedly elevated during H5N1 influenza virus infection, the “cytokine storm” is hypothesized to be the main cause of mortality. Here, we demonstrate that...

Persistent Host Markers in Pandemic and H5N1 Influenza Viruses▿

Finkelstein, David B., Mukatira, Suraj, Mehta, Perdeep K., Obenauer, John C., Su, Xiaoping, Webster, Robert G., ...

Avian influenza viruses have adapted to human hosts, causing pandemics in humans. The key host-specific amino acid mutations required for an avian influenza virus to function in humans are unknown....

The polymerase complex genes contribute to the high virulence of the human H5N1 influenza virus isolate A/Vietnam/1203/04

Salomon, Rachelle, Franks, John, Govorkova, Elena A., Ilyushina, Natalia A., Yen, Hui-Ling, Hulse-Post, Diane J., ...

H5N1 influenza viruses transmitted from poultry to humans in Asia cause high mortality and pose a pandemic threat. Viral genes important for cell tropism and replication efficiency must be identified...

Higher polymerase activity of a human influenza virus enhances activation of the hemagglutinin-induced Raf/MEK/ERK signal cascade

Marjuki, Henju, Yen, Hui-Ling, Franks, John, Webster, Robert G, Pleschka, Stephan, Hoffmann, Erich

Influenza viruses replicate within the nucleus of infected cells. Viral genomic RNA, three polymerase subunits (PB2, PB1, and PA), and the nucleoprotein (NP) form ribonucleoprotein complexes (RNPs)...

Neuraminidase Inhibitor-Resistant Recombinant A/Vietnam/1203/04 (H5N1) Influenza Viruses Retain Their Replication Efficiency and Pathogenicity In Vitro and In Vivo▿

Yen, Hui-Ling, Ilyushina, Natalia A., Salomon, Rachelle, Hoffmann, Erich, Webster, Robert G., Govorkova, Elena A.

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 influenza...

Epitope Mapping of the Hemagglutinin Molecule of a Highly Pathogenic H5N1 Influenza Virus by Using Monoclonal Antibodies▿

Kaverin, Nikolai V., Rudneva, Irina A., Govorkova, Elena A., Timofeeva, Tatyana A., Shilov, Aleksandr A., Kochergin-Nikitsky, Konstantin S., ...

We mapped the hemagglutinin (HA) antigenic epitopes of a highly pathogenic H5N1 influenza virus on the three-dimensional HA structure by characterizing escape mutants of a recombinant virus...

Human-Like Receptor Specificity Does Not Affect the Neuraminidase-Inhibitor Susceptibility of H5N1 Influenza Viruses

Ilyushina, Natalia A., Govorkova, Elena A., Gray, Thomas E., Bovin, Nicolai V., Webster, Robert G.

If highly pathogenic H5N1 influenza viruses acquire affinity for human rather than avian respiratory epithelium, will their susceptibility to neuraminidase (NA) inhibitors (the likely first line of...

Antigenic Profile of Avian H5N1 Viruses in Asia from 2002 to 2007▿

Wu, Wai Lan, Chen, Yixin, Wang, Pui, Song, Wenjun, Lau, Siu-Ying, Rayner, Jane M., ...

Antigenic profiles of post-2002 H5N1 viruses representing major genetic clades and various geographic sources were investigated using a panel of 17 monoclonal antibodies raised from five H5N1...

Oseltamivir-Ribavirin Combination Therapy for Highly Pathogenic H5N1 Influenza Virus Infection in Mice▿

Ilyushina, Natalia A., Hay, Alan, Yilmaz, Neziha, Boon, Adrianus C. M., Webster, Robert G., Govorkova, Elena A.

We studied the effects of a neuraminidase inhibitor (oseltamivir) and an inhibitor of influenza virus polymerases (ribavirin) against two highly pathogenic H5N1 influenza viruses. In vitro,...

Pathogenicity and Vaccine Efficacy of Different Clades of Asian H5N1 Avian Influenza A Viruses in Domestic Ducks ▿

Kim, Jeong-Ki, Seiler, Patrick, Forrest, Heather L., Khalenkov, Alexey M., Franks, John, Kumar, Mahesh, ...

Waterfowl represent the natural reservoir of all subtypes of influenza A viruses, including H5N1. Ducks are especially considered major contributors to the spread of H5N1 influenza A viruses because...

A new avian influenza virus from feral birds in the USSR: Recombination in nature?

Webster, Robert G., Isachenko, Valentina A., Carter, Martha

Six avian influenza A viruses isolated in the USSR were characterized antigenically by using specific antisera to the isolated surface subunits of the known reference strains. Three of the viruses,...

Immunological interrelationships of Hong Kong, Asian and Equi-2 influenza viruses in man*

Marine, William M., Workman, Wilton M., Webster, Robert G.

Sera from an elderly population drawn prior to the 1968 Hong Kong influenza epidemic were found to have a high prevalence of Hong Kong antibody, indicating the circulation of a Hong Kong-like virus...

What Is the Optimal Therapy for Patients with H5N1 Influenza?

White, Nicholas J., Webster, Robert G., Govorkova, Elena A., Uyeki, Timothy M.

Nicholas White discusses optimal dosing of oseltamivir, Robert Webster and Elena Govorkova discuss combination antiviral therapy, and Timothy Uyeki discusses clinical care of patients with H5N1.

Changes in H5N1 influenza virus hemagglutinin receptor binding domain affect systemic spread

Yen, Hui-Ling, Aldridge, Jerry R., Boon, Adrianus C. M., Ilyushina, Natalia A., Salomon, Rachelle, Hulse-Post, Diane J., ...

The HA of influenza virus is a receptor-binding and fusion protein that is required to initiate infection. The HA receptor-binding domain determines the species of sialyl receptors recognized by...

Dating the emergence of pandemic influenza viruses

Smith, Gavin J. D., Bahl, Justin, Vijaykrishna, Dhanasekaran, Zhang, Jinxia, Poon, Leo L. M., Chen, Honglin, ...

Pandemic influenza viruses cause significant mortality in humans. In the 20th century, 3 influenza viruses caused major pandemics: the 1918 H1N1 virus, the 1957 H2N2 virus, and the 1968 H3N2 virus....

Influenza (H5N1) Viruses in Poultry, Russian Federation, 2005–2006

Lipatov, Aleksandr S., Evseenko, Vasily A., Yen, Hui-Ling, Zaykovskaya, Anna V., Durimanov, Alexander G., Zolotykh, Sergey I., ...

Migrating waterfowl may be the primary source of influenza (H5N1) in western Siberia and the European part of the Russian Federation.

TNF/iNOS-producing dendritic cells are the necessary evil of lethal influenza virus infection

Aldridge, Jerry R., Moseley, Carson E., Boltz, David A., Negovetich, Nicholas J., Reynolds, Cory, Franks, John, ...

Respiratory infection with highly pathogenic influenza A viruses is characterized by the exuberant production of cytokines and chemokines and the enhanced recruitment of innate inflammatory cells....

Amino Acid Residues in the Fusion Peptide Pocket Regulate the pH of Activation of the H5N1 Influenza Virus Hemagglutinin Protein▿

Reed, Mark L., Yen, Hui-Ling, DuBois, Rebecca M., Bridges, Olga A., Salomon, Rachelle, Webster, Robert G., ...

The receptor specificity and cleavability of the hemagglutinin (HA) protein have been shown to regulate influenza A virus transmissibility and pathogenicity, but little is known about how its pH of...

Isolation and Genetic Characterization of H5N2 Influenza Viruses from Pigs in Korea ▿

Lee, Jun Han, Pascua, Philippe Noriel Q., Song, Min-Suk, Baek, Yun Hee, Kim, Chul-Joong, Choi, Hwan-Woon, ...

Due to dual susceptibility to both human and avian influenza A viruses, pigs are believed to be effective intermediate hosts for the spread and production of new viruses with pandemic potential. In...