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

ABSTRACT 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 markets showed no disease signs. At this time, H9N2 influenza viruses were cocirculating in the markets. We investigated the role of H9N2 influenza viruses in protecting chickens from lethal H5N1 influenza virus infections. Sera from chickens infected with an H9N2 influenza virus did not cross-react with an H5N1 influenza virus in neutralization or hemagglutination inhibition assays. Most chickens primed with an H9N2 influenza virus 3 to 70 days earlier survived the lethal challenge of an H5N1 influenza virus, but infected birds shed H5N1 influenza virus in their feces. Adoptive transfer of T lymphocytes or CD8+ T cells from inbred chickens (B2/B2) infected with an H9N2 influenza virus to naive inbred chickens (B2/B2) protected them from lethal H5N1 influenza virus. In vitro cytotoxicity assays showed that T lymphocytes or CD8+ T cells from chickens infected with an H9N2 influenza virus recognized target cells infected with either an H5N1 or H9N2 influenza virus in a dose-dependent manner. Our findings indicate that cross-reactive cellular immunity induced by H9N2 influenza viruses protected chickens from lethal infection with H5N1 influenza viruses in the Hong Kong markets in 1997 but permitted virus shedding in the feces. Our findings are the first to suggest that cross-reactive cellular immunity can change the outcome of avian influenza virus infection in birds in live markets and create a situation for the perpetuation of H5N1 influenza viruses.

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Host DNA released by NETosis in neutrophils exposed to seasonal H1N1 and highly pathogenic H5N1 influenza viruses

10.21203/rs.2.24164/v1 ◽

2020 ◽

Author(s):

Louisa L.Y. Chan ◽

John M. Nicholls ◽

J.S. Malik Peiris ◽

Yu Lung Lau ◽

Michael C.W. Chan ◽

...

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

H1n1 Virus ◽

Influenza Virus Infection ◽

Alveolar Epithelium ◽

Influenza Viruses ◽

H5n1 Influenza Virus ◽

H5n1 Influenza ◽

Influenza H1n1

Abstract Background Neutrophil (Nϕ) is of the most abundant number in human immune system. During acute influenza virus infection, Nϕs are already active in the early phase of inflammation-a time in which clinical biopsy or autopsy material is not readily available. However, the role of Nϕ in virus infection is not well understood. Here, we studied the role of Nϕ in host defense during influenza A virus infection, specifically assessing if it contributes to the differential pathogenesis in H5N1 disease. Methods Nϕs were freshly isolated from healthy volunteers and subjected to direct influenza H1N1 and H5N1 virus infection in vitro . The ability of the naïve Nϕs to infiltrate from the basolateral to the apical phase of the influenza virus infected alveolar epithelium was assessed. The viral replication, innate immune responses and Neutrophil extracellular trap (NET) formation of Nϕs upon influenza virus infection were evaluated. Results Our results demonstrated that influenza virus infected alveolar epithelium allowed more Nϕs transmigration. Significantly more Nϕs migrated across the H5N1 influenza virus infected the epithelium than the counterpart infected by the seasonal influenza H1N1 virus infected. Nϕs were equally susceptible to H5N1 and H1N1 virus infection with similar viral gene transcription. Productive replication was observed in H5N1 infected Nϕs. Both H5N1 and H1N1 infected Nϕs induced cytokines and chemokines including TNF-α, IFN-β, CXCL10, MIP-1α and IL-8. This inferred a more intense inflammatory response posed by H5N1 than H1N1 virus. Strikingly, NADPH oxidase-independent NET formation was observed in H1N1 infected Nϕs at 6 hpi while no NET formation was observed upon H5N1 infection. Conclusion Our data is the first to demonstrate that NET formation is abrogated in H5N1 influenza virus infection. Its contribution to the differential severity of H5N1 disease requires further investigation.

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Antibodies and CD4+ T-cells mediate cross-protection against H5N1 influenza virus infection in mice after vaccination with a low pathogenic H5N2 strain

Vaccine ◽

10.1016/j.vaccine.2008.09.051 ◽

2008 ◽

Vol 26 (52) ◽

pp. 6965-6974 ◽

Cited By ~ 26

Author(s):

Karoline Droebner ◽

Emanuel Haasbach ◽

Cordula Fuchs ◽

Andreas O. Weinzierl ◽

Stefan Stevanovic ◽

...

Keyword(s):

T Cells ◽

Influenza Virus ◽

Virus Infection ◽

Cd4 T Cells ◽

Influenza Virus Infection ◽

Cross Protection ◽

H5n1 Influenza Virus ◽

H5n1 Influenza

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

Antiviral Research ◽

10.1016/j.antiviral.2007.01.020 ◽

2007 ◽

Vol 74 (3) ◽

pp. A31-A32 ◽

Cited By ~ 2

Author(s):

N ILYUSHINA ◽

R WEBSTER ◽

E GOVORKOVA

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Combination Therapy ◽

Influenza Virus Infection ◽

H5n1 Influenza Virus ◽

Highly Pathogenic ◽

H5n1 Influenza ◽

Pathogenic H5n1

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Kinetic Characterization of PB1-F2-Mediated Immunopathology during Highly Pathogenic Avian H5N1 Influenza Virus Infection

PLoS ONE ◽

10.1371/journal.pone.0057894 ◽

2013 ◽

Vol 8 (3) ◽

pp. e57894 ◽

Cited By ~ 21

Author(s):

Olivier Leymarie ◽

Grégory Jouvion ◽

Pierre-Louis Hervé ◽

Christophe Chevalier ◽

Valérie Lorin ◽

...

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Influenza Virus Infection ◽

Kinetic Characterization ◽

H5n1 Influenza Virus ◽

Highly Pathogenic ◽

H5n1 Influenza ◽

Avian H5n1 Influenza Virus

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Nanobodies With In Vitro Neutralizing Activity Protect Mice Against H5N1 Influenza Virus Infection

The Journal of Infectious Diseases ◽

10.1093/infdis/jiq168 ◽

2011 ◽

Vol 203 (8) ◽

pp. 1063-1072 ◽

Cited By ~ 48

Author(s):

Lorena Itatí Ibañez ◽

Marina De Filette ◽

Anna Hultberg ◽

Theo Verrips ◽

Nigel Temperton ◽

...

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Influenza Virus Infection ◽

H5n1 Influenza Virus ◽

Neutralizing Activity ◽

H5n1 Influenza

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Viral Replication Rate Regulates Clinical Outcome and CD8 T Cell Responses during Highly Pathogenic H5N1 Influenza Virus Infection in Mice

PLoS Pathogens ◽

10.1371/journal.ppat.1001139 ◽

2010 ◽

Vol 6 (10) ◽

pp. e1001139 ◽

Cited By ~ 45

Author(s):

Yasuko Hatta ◽

Karen Hershberger ◽

Kyoko Shinya ◽

Sean C. Proll ◽

Richard R. Dubielzig ◽

...

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Influenza Virus Infection ◽

Cd8 T Cell ◽

H5n1 Influenza Virus ◽

Replication Rate ◽

Highly Pathogenic ◽

Cell Responses ◽

H5n1 Influenza ◽

Pathogenic H5n1

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

Journal of Virology ◽

10.1128/jvi.78.9.4892-4901.2004 ◽

2004 ◽

Vol 78 (9) ◽

pp. 4892-4901 ◽

Cited By ~ 271

Author(s):

Katharine M. Sturm-Ramirez ◽

Trevor Ellis ◽

Barry Bousfield ◽

Lucy Bissett ◽

Kitman Dyrting ◽

...

Keyword(s):

Influenza Virus ◽

Hong Kong ◽

Influenza A ◽

Influenza Virus Infection ◽

Influenza Viruses ◽

Neurological Dysfunction ◽

Aquatic Birds ◽

Antigenic Analysis ◽

Highly Pathogenic ◽

H5n1 Influenza

ABSTRACT 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 caused deaths among wild migratory birds and resident waterfowl, including ducks, in two Hong Kong parks. In February 2003, an avian H5N1 virus closely related to one of these viruses was isolated from two humans with acute respiratory distress, one of whom died. Antigenic analysis of the new avian isolates showed a reactivity pattern different from that of H5N1 viruses isolated in 1997 and 2001. This finding suggests that significant antigenic variation has recently occurred among H5N1 viruses. We inoculated mallards with antigenically different H5N1 influenza viruses isolated between 1997 and 2003. The new 2002 avian isolates caused systemic infection in the ducks, with high virus titers and pathology in multiple organs, particularly the brain. Ducks developed acute disease, including severe neurological dysfunction and death. Virus was also isolated at high titers from the birds' drinking water and from contact birds, demonstrating efficient transmission. In contrast, H5N1 isolates from 1997 and 2001 were not consistently transmitted efficiently among ducks and did not cause significant disease. Despite a high level of genomic homology, the human isolate showed striking biological differences from its avian homologue in a duck model. This is the first reported case of lethal influenza virus infection in wild aquatic birds since 1961.

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