Pathobiology of A/Chicken/Hong Kong/220/97 (H5N1) Avian Influenza Virus in Seven Gallinaceous Species

Direct bird-to-human transmission, with the production of severe respiratory disease and human mortality, is unique to the Hong Kong-origin H5N1 highly pathogenic avian influenza (HPAI) virus, which was originally isolated from a disease outbreak in chickens. The pathobiology of the A/chicken/Hong Kong/ 220/97 (H5N1) (HK/220) HPAI virus was investigated in chickens, turkeys, Japanese and Bobwhite quail, guinea fowl, pheasants, and partridges, where it produced 75-100% mortality within 10 days. Depression, mucoid diarrhea, and neurologic dysfunction were common clinical manifestations of disease. Grossly, the most severe and consistent lesions included splenomegaly, pulmonary edema and congestion, and hemorrhages in enteric lymphoid areas, on serosal surfaces, and in skeletal muscle. Histologic lesions were observed in multiple organs and were characterized by exudation, hemorrhage, necrosis, inflammation, or a combination of these features. The lung, heart, brain, spleen, and adrenal glands were the most consistently affected, and viral antigen was most often detected by immunohistochemistry in the parenchyma of these organs. The pathogenesis of infection with the HK/220 HPAI virus in these species was twofold. Early mortality occurring at 1-2 days postinoculation (DPI) corresponded to severe pulmonary edema and congestion and virus localization within the vascular endothelium. Mortality occurring after 2 DPI was related to systemic biochemical imbalance, multiorgan failure, or a combination of these factors. The pathobiologic features were analogous to those experimentally induced with other HPAI viruses in domestic poultry.

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Continued Circulation in China of Highly Pathogenic Avian Influenza Viruses Encoding the Hemagglutinin Gene Associated with the 1997 H5N1 Outbreak in Poultry and Humans

Journal of Virology ◽

10.1128/jvi.74.14.6592-6599.2000 ◽

2000 ◽

Vol 74 (14) ◽

pp. 6592-6599 ◽

Cited By ~ 123

Author(s):

Angela N. Cauthen ◽

David E. Swayne ◽

Stacey Schultz-Cherry ◽

Michael L. Perdue ◽

David L. Suarez

Keyword(s):

Influenza Virus ◽

Hong Kong ◽

Avian Influenza ◽

Avian Influenza Virus ◽

Clinical Signs ◽

Influenza Viruses ◽

Highly Pathogenic ◽

H5n1 Avian Influenza Virus ◽

H5n1 Avian Influenza ◽

Viral Isolates

ABSTRACT Since the outbreak in humans of an H5N1 avian influenza virus in Hong Kong in 1997, poultry entering the live-bird markets of Hong Kong have been closely monitored for infection with avian influenza. In March 1999, this monitoring system detected geese that were serologically positive for H5N1 avian influenza virus, but the birds were marketed before they could be sampled for virus. However, viral isolates were obtained by swabbing the cages that housed the geese. These samples, known collectively as A/Environment/Hong Kong/437/99 (A/Env/HK/437/99), contained four viral isolates, which were compared to the 1997 H5N1 Hong Kong isolates. Analysis of A/Env/HK/437/99 viruses revealed that the four isolates are nearly identical genetically and are most closely related to A/Goose/Guangdong/1/96. These isolates and the 1997 H5N1 Hong Kong viruses encode common hemagglutinin (H5) genes that have identical hemagglutinin cleavage sites. Thus, the pathogenicity of the A/Env/HK/437/99 viruses was compared in chickens and in mice to evaluate the potential for disease outbreaks in poultry and humans. The A/Env/HK/437/99 isolates were highly pathogenic in chickens but caused a longer mean death time and had altered cell tropism compared to A/Hong Kong/156/97 (A/HK/156/97). Like A/HK/156/97, the A/Env/HK/437/99 viruses replicated in mice and remained localized to the respiratory tract. However, the A/Env/HK/437/99 isolates caused only mild pathological lesions in these tissues and no clinical signs of disease or death. As a measure of the immune response to these viruses, transforming growth factor β levels were determined in the serum of infected mice and showed elevated levels for the A/Env/HK/437/99 viruses compared to the A/HK/156/97 viruses. This study is the first to characterize the A/Env/HK/437/99 viruses in both avian and mammalian species, evaluating the H5 gene from the 1997 Hong Kong H5N1 isolates in a different genetic background. Our findings reveal that at least one of the avian influenza virus genes encoded by the 1997 H5N1 Hong Kong viruses continues to circulate in mainland China and that this gene is important for pathogenesis in chickens but is not the sole determinant of pathogenicity in mice. There is evidence that H9N2 viruses, which have internal genes in common with the 1997 H5N1 Hong Kong isolates, are still circulating in Hong Kong and China as well, providing a heterogeneous gene pool for viral reassortment. The implications of these findings for the potential for human disease are discussed.

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Retraction notice to “Modified Newcastle disease virus vectors expressing the H5 hemagglutinin induce enhanced protection against highly pathogenic H5N1 avian influenza virus in chickens” [Vaccine 32(35) (2014) 4428–4435]

Vaccine ◽

10.1016/j.vaccine.2020.12.068 ◽

2021 ◽

Vol 39 (4) ◽

pp. 775

Author(s):

Shin-Hee Kim ◽

Anandan Paldurai ◽

Sa Xiao ◽

Peter L. Collins ◽

Siba K. Samal

Keyword(s):

Influenza Virus ◽

Avian Influenza ◽

Newcastle Disease Virus ◽

Avian Influenza Virus ◽

Newcastle Disease ◽

Highly Pathogenic ◽

H5n1 Avian Influenza Virus ◽

H5n1 Avian Influenza ◽

Retraction Notice ◽

Pathogenic H5n1

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PA-X-associated early alleviation of the acute lung injury contributes to the attenuation of a highly pathogenic H5N1 avian influenza virus in mice

Medical Microbiology and Immunology ◽

10.1007/s00430-016-0461-2 ◽

2016 ◽

Vol 205 (4) ◽

pp. 381-395 ◽

Cited By ~ 16

Author(s):

Jiao Hu ◽

Yiqun Mo ◽

Zhao Gao ◽

Xiaoquan Wang ◽

Min Gu ◽

...

Keyword(s):

Influenza Virus ◽

Acute Lung Injury ◽

Lung Injury ◽

Avian Influenza ◽

Avian Influenza Virus ◽

Highly Pathogenic ◽

H5n1 Avian Influenza Virus ◽

H5n1 Avian Influenza ◽

Pathogenic H5n1

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Analysis of the crow lung transcriptome in response to infection with highly pathogenic H5N1 avian influenza virus

Gene ◽

10.1016/j.gene.2015.01.016 ◽

2015 ◽

Vol 559 (1) ◽

pp. 77-85 ◽

Cited By ~ 16

Author(s):

Periyasamy Vijayakumar ◽

Anamika Mishra ◽

Pradip B. Ranaware ◽

Atul P. Kolte ◽

Diwakar D. Kulkarni ◽

...

Keyword(s):

Influenza Virus ◽

Avian Influenza ◽

Avian Influenza Virus ◽

Highly Pathogenic ◽

H5n1 Avian Influenza Virus ◽

H5n1 Avian Influenza ◽

Pathogenic H5n1

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An inactivated H5N2 vaccine reduces transmission of highly pathogenic H5N1 avian influenza virus among native chickens

Vaccine ◽

10.1016/j.vaccine.2009.02.085 ◽

2009 ◽

Vol 27 (21) ◽

pp. 2864-2869 ◽

Cited By ~ 28

Author(s):

O.N. Poetri ◽

A. Bouma ◽

Sri Murtini ◽

I. Claassen ◽

G. Koch ◽

...

Keyword(s):

Influenza Virus ◽

Avian Influenza ◽

Avian Influenza Virus ◽

Highly Pathogenic ◽

H5n1 Avian Influenza Virus ◽

H5n1 Avian Influenza ◽

Native Chickens ◽

Pathogenic H5n1

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Highly Pathogenic H5N1 Avian Influenza Virus Induces Extracellular Ca2+ Influx, Leading to Apoptosis in Avian Cells

Journal of Virology ◽

10.1128/jvi.01923-09 ◽

2010 ◽

Vol 84 (6) ◽

pp. 3068-3078 ◽

Cited By ~ 37

Author(s):

Mayo Ueda ◽

Tomo Daidoji ◽

Anariwa Du ◽

Cheng-Song Yang ◽

Madiha S. Ibrahim ◽

...

Keyword(s):

Influenza Virus ◽

Avian Influenza ◽

Avian Influenza Virus ◽

Influenza A Virus ◽

Influenza A ◽

Highly Pathogenic ◽

H5n1 Avian Influenza Virus ◽

H5n1 Avian Influenza ◽

Infected Cells ◽

Pathogenic H5n1

ABSTRACT In this study, we show that the highly pathogenic H5N1 avian influenza virus (AIV) (A/crow/Kyoto/53/04 and A/chicken/Egypt/CL6/07) induced apoptosis in duck embryonic fibroblasts (DEF). In contrast, apoptosis was reduced among cells infected with low-pathogenic AIVs (A/duck/HK/342/78 [H5N2], A/duck/HK/820/80 [H5N3], A/wigeon/Osaka/1/01 [H7N7], and A/turkey/Wisconsin/1/66 [H9N2]). Thus, we investigated the molecular mechanisms of apoptosis induced by H5N1-AIV infection. Caspase-dependent and -independent pathways contributed to the cytopathic effects. We further showed that, in the induction of apoptosis, the hemagglutinin of H5N1-AIV played a major role and its cleavage sequence was not critical. We also observed outer membrane permeabilization and loss of the transmembrane potential of the mitochondria of infected DEF, indicating that mitochondrial dysfunction was caused by the H5N1-AIV infection. We then analyzed Ca2+ dynamics in the infected cells and demonstrated an increase in the concentration of Ca2+ in the cytosol ([Ca2+]i) and mitochondria ([Ca2+]m) after H5N1-AIV infection. Regardless, gene expression important for regulating Ca2+ efflux from the endoplasmic reticulum did not significantly change after H5N1-AIV infection. These results suggest that extracellular Ca2+ may enter H5N1-AIV-infected cells. Indeed, EGTA, which chelates extracellular free Ca2+, significantly reduced the [Ca2+]i, [Ca2+]m, and apoptosis induced by H5N1-AIV infection. In conclusion, we identified a novel mechanism for influenza A virus-mediated cell death, which involved the acceleration of extracellular Ca2+ influx, leading to mitochondrial dysfunction and apoptosis. These findings may be useful for understanding the pathogenesis of H5N1-AIV in avian species as well as the impact of Ca2+ homeostasis on influenza A virus infection.

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