Dataset Information

Continued circulation in China of highly pathogenic avian influenza viruses encoding the hemagglutinin gene associated with the 1997 H5N1 outbreak in poultry and humans.

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 beta 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.

SUBMITTER: Cauthen AN

PROVIDER: S-EPMC112169 | biostudies-literature | 2000 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Continued circulation in China of highly pathogenic avian influenza viruses encoding the hemagglutinin gene associated with the 1997 H5N1 outbreak in poultry and humans.

Cauthen A N AN Swayne D E DE Schultz-Cherry S S Perdue M L ML Suarez D L DL

Journal of virology 20000701 14

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 collective ...[more]

PMID: 10864673

Similar Datasets

Project description:The genesis of novel influenza viruses through reassortment poses a continuing risk to public health. This is of particular concern in Bangladesh, where highly pathogenic avian influenza viruses of the A(H5N1) subtype are endemic and cocirculate with other influenza viruses. Active surveillance of avian influenza viruses in Bangladeshi live poultry markets detected three A(H5) genotypes, designated H5N1-R1, H5N1-R2, and H5N2-R3, that arose from reassortment of A(H5N1) clade 2.3.2.1a viruses. The H5N1-R1 and H5N1-R2 viruses contained HA, NA, and M genes from the A(H5N1) clade 2.3.2.1a viruses and PB2, PB1, PA, NP, and NS genes from other Eurasian influenza viruses. H5N2-R3 viruses contained the HA gene from circulating A(H5N1) clade 2.3.2.1a viruses, NA and M genes from concurrently circulating A(H9N2) influenza viruses, and PB2, PB1, PA, NP, and NS genes from other Eurasian influenza viruses. Representative viruses of all three genotypes and a parental clade 2.3.2.1a strain (H5N1-R0) infected and replicated in mice without prior adaptation; the H5N2-R3 virus replicated to the highest titers in the lung. All viruses efficiently infected and killed chickens. All viruses replicated in inoculated ferrets, but no airborne transmission was detected, and only H5N2-R3 showed limited direct-contact transmission. Our findings demonstrate that although the A(H5N1) viruses circulating in Bangladesh have the capacity to infect and replicate in mammals, they show very limited capacity for transmission. However, reassortment does generate viruses of distinct phenotypes.IMPORTANCE Highly pathogenic avian influenza A(H5N1) viruses have circulated continuously in Bangladesh since 2007, and active surveillance has detected viral evolution driven by mutation and reassortment. Recently, three genetically distinct A(H5N1) reassortant viruses were detected in live poultry markets in Bangladesh. Currently, we cannot assign pandemic risk by only sequencing viruses; it must be conducted empirically. We found that the H5Nx highly pathogenic avian influenza viruses exhibited high virulence in mice and chickens, and one virus had limited capacity to transmit between ferrets, a property considered consistent with a higher zoonotic risk.

Project description:BackgroundOngoing outbreaks of H5N1 highly pathogenic avian influenza (HPAI) viruses and the emergence of the genetic-related hemagglutinin (HA) gene of reassortant H5Nx viruses currently circulating in wild birds and poultries pose a great global public health concern. In this study, we comprehensively analyzed the genetic evolution of Thai H5N1 HA and neuraminidase (NA) genes between 2003 and 2010. The H5N1 Thailand virus clade 2.3.4 was also genetically compared to the currently circulating clade 2.3.4.4 of H5Nx viruses.MethodsFull-length nucleotide sequences of 178 HA and 143 NA genes of H5N1 viruses circulating between 2003 and 2010 were phylogenetically analyzed using maximum likelihood (ML) phylogenetic construction. Bayesian phylogenetic trees were reconstructed using BEAST analysis with a Bayesian Markov chain Monte Carlo (MCMC) approach. The maximum clade credibility (MCC) tree was determined, and the time of the most recent common ancestor (tMRCA) was estimated. The H5N1 HA nucleotide sequences of clade 2.3.4 Thailand viruses were phylogenetically analyzed using ML phylogenetic tree construction and analyzed for nucleotide similarities with various subtypes of reassortant H5Nx HA clade 2.3.4.4.ResultsML phylogenetic analysis revealed two distinct HA clades, clade 1 and clade 2.3.4, and two distinct NA groups within the corresponding H5 clade 1 viruses. Bayesian phylogenetic reconstruction for molecular clock suggested that the Thai H5N1 HA and NA emerged in 2001.87 (95% HPD: 2001.34-2002.49) and 2002.38 (95% HPD: 2001.99-2002.82), respectively, suggesting that the virus existed before it was first reported in 2004. The Thai H5N1 HA clade 2.3.4 was grouped into corresponding clades 2.3.4, 2.3.4.1, 2.3.4.2, and 2.3.4.3, and shared nucleotide similarities to reassortant H5Nx clade 2.3.4.4 ranged from 92.4-96.8%. Phylogenetic analysis revealed monophyletic H5Nx clade 2.3.4.4 evolved from H5N1 clade 2.3.4.ConclusionH5N1 viruses existed, and were presumably introduced and circulated in avian species in Thailand, before they were officially reported in 2004. HA and NA genes continuously evolved during circulation between 2004 and 2010. This study provides a better understanding of genetic evolution with respect to molecular epidemiology. Monitoring and surveillance of emerging variants/reassortants should be continued.

Dataset Information

Continued circulation in China of highly pathogenic avian influenza viruses encoding the hemagglutinin gene associated with the 1997 H5N1 outbreak in poultry and humans.

Publications

Continued circulation in China of highly pathogenic avian influenza viruses encoding the hemagglutinin gene associated with the 1997 H5N1 outbreak in poultry and humans.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets