Dataset Information

Genetics, Receptor Binding, Replication, and Mammalian Transmission of H4 Avian Influenza Viruses Isolated from Live Poultry Markets in China.

ABSTRACT: Unlabelled: H4 avian influenza virus (AIV) is one of the most prevalent influenza virus subtypes in the world. However, whether H4 AIVs pose a threat to public health remains largely unclear. Here, we analyzed the phylogenetic relationships, receptor binding properties, replication, and transmissibility in mammals of H4 AIVs isolated from live poultry markets in China between 2009 and 2012. Genomic sequence analysis of 36 representative H4 viruses revealed 32 different genotypes, indicating that these viruses are undergoing complex and frequent reassortment events. All 32 viruses tested could replicate in the respiratory organs of infected mice without prior adaptation. Receptor binding analysis demonstrated that the H4 AIVs bound to ?-2,6-linked glycans, although they retained the binding preference for ?-2,3-linked glycans. When we tested the direct-contact transmission of 10 H4 viruses in guinea pigs, we found that three viruses did not transmit to any of the contact animals, one virus transmitted to one of three contact animals, and six viruses transmitted to all three contact animals. When we further tested the respiratory droplet transmissibility of four of the viruses that transmitted efficiently via direct contact, we found that three of them could transmit to one or two of the five exposed animals. Our study demonstrates that the current circulating H4 AIVs can infect, replicate in, and transmit to mammalian hosts, thereby posing a potential threat to human health. These findings emphasize the continual need for enhanced surveillance of H4 AIVs.

Importance: Numerous surveillance studies have documented the wide distribution of H4 AIVs throughout the world, yet the biological properties of H4 viruses have not been well studied. In this study, we found that multiple genotypes of H4 viruses are cocirculating in the live poultry markets of China and that H4 viruses can replicate in mice, possess human-type receptor binding specificity, and transmit between guinea pigs via direct contact. Strikingly, some H4 strains also can transmit via respiratory droplet, albeit with limited efficiency. These results clearly show the potential threat posed by H4 viruses to public health.

SUBMITTER: Liang L

PROVIDER: S-EPMC4719592 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Publications

Genetics, Receptor Binding, Replication, and Mammalian Transmission of H4 Avian Influenza Viruses Isolated from Live Poultry Markets in China.

Liang Libin L Deng Guohua G Shi Jianzhong J Wang Shuai S Zhang Qianyi Q Kong Huihui H Gu Chunyang C Guan Yuntao Y Suzuki Yasuo Y Li Yanbing Y Jiang Yongping Y Tian Guobin G Liu Liling L Li Chengjun C Chen Hualan H

Journal of virology 20151118 3

<h4>Unlabelled</h4>H4 avian influenza virus (AIV) is one of the most prevalent influenza virus subtypes in the world. However, whether H4 AIVs pose a threat to public health remains largely unclear. Here, we analyzed the phylogenetic relationships, receptor binding properties, replication, and transmissibility in mammals of H4 AIVs isolated from live poultry markets in China between 2009 and 2012. Genomic sequence analysis of 36 representative H4 viruses revealed 32 different genotypes, indicati ...[more]

PMID: 26581996

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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:BackgroundTransmission of the novel avian influenza A H7N9 virus seems to be predominantly between poultry and people. In the major Chinese cities of Shanghai, Hangzhou, Huzhou, and Nanjing--where most human cases of infection have occurred--live poultry markets (LPMs) were closed in April, 2013, soon after the initial outbreak, as a precautionary public health measure. Our objective was to quantify the effect of LPM closure in these cities on poultry-to-person transmission of avian influenza A H7N9 virus.MethodsWe obtained information about every laboratory-confirmed human case of avian influenza A H7N9 virus infection reported in the four cities by June 7, 2013, from a database built by the Chinese Center for Disease Control and Prevention. We used data for age, sex, location, residence type (rural or urban area), and dates of illness onset. We obtained information about LPMs from official sources. We constructed a statistical model to explain the patterns in incidence of cases reported in each city on the basis of the assumption of a constant force of infection before LPM closure, and a different constant force of infection after closure. We fitted the model with Markov chain Monte Carlo methods.Findings85 human cases of avian influenza A H7N9 virus infection were reported in Shanghai, Hangzhou, Huzhou, and Nanjing by June 7, 2013, of which 60 were included in our main analysis. Closure of LPMs reduced the mean daily number of infections by 99% (95% credibility interval 93-100%) in Shanghai, by 99% (92-100%) in Hangzhou, by 97% (68-100%) in Huzhou, and by 97% (81-100%) in Nanjing. Because LPMs were the predominant source of exposure to avian influenza A H7N9 virus for confirmed cases in these cities, we estimated that the mean incubation period was 3·3 days (1·4-5·7).InterpretationLPM closures were effective in the control of human risk of avian influenza A H7N9 virus infection in the spring of 2013. In the short term, LPM closure should be rapidly implemented in areas where the virus is identified in live poultry or people. In the long term, evidence-based discussions and deliberations about the role of market rest days and central slaughtering of all live poultry should be renewed.FundingMinistry of Science and Technology, China; Research Fund for the Control of Infectious Disease; Hong Kong University Grants Committee; China-US Collaborative Program on Emerging and Re-emerging Infectious Diseases; Harvard Center for Communicable Disease Dynamics; and the US National Institutes of Health.

Dataset Information

Genetics, Receptor Binding, Replication, and Mammalian Transmission of H4 Avian Influenza Viruses Isolated from Live Poultry Markets in China.

Publications

Genetics, Receptor Binding, Replication, and Mammalian Transmission of H4 Avian Influenza Viruses Isolated from Live Poultry Markets in China.

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