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PLoS ONE. Characterization of an Artificial Swine-Origin Influenza Virus with the Same Gene Combination as H1N1/2009 Virus: A Genesis Clue of Pandemic Strain
[Source: PLoS ONE, full text: (LINK). Abstract, edited.]
Characterization of an Artificial Swine-Origin Influenza Virus with the Same Gene Combination as H1N1/2009 Virus: A Genesis Clue of Pandemic Strain
Xueli Zhao<SUP>1</SUP><SUP>#</SUP>, Yipeng Sun<SUP>1</SUP><SUP>#</SUP>, Juan Pu<SUP>1</SUP>, Lihong Fan<SUP>1</SUP>, Weimin Shi<SUP>1</SUP>, Yanxin Hu<SUP>1</SUP>, Jun Yang<SUP>1</SUP>, Qi Xu<SUP>1</SUP>, Jingjing Wang<SUP>1</SUP>, Dongjun Hou<SUP>1</SUP>, Guangpeng Ma<SUP>2</SUP><SUP>*</SUP>, Jinhua Liu<SUP>1</SUP><SUP>,</SUP><SUP>3</SUP><SUP>*</SUP>
1 Key Laboratory of Zoonosis of Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, China, 2 China Rural Technology Development Center, Beijing, China, 3 The Shandong Animal Disease Control Center, Jinan, Shandong, China
Abstract
Pandemic H1N1/2009 influenza virus, derived from a reassortment of avian, human, and swine influenza viruses, possesses a unique gene segment combination that had not been detected previously in animal and human populations. Whether such a gene combination could result in the pathogenicity and transmission as H1N1/2009 virus remains unclear. In the present study, we used reverse genetics to construct a reassortant virus (rH1N1) with the same gene combination as H1N1/2009 virus (NA and M genes from a Eurasian avian-like H1N1 swine virus and another six genes from a North American triple-reassortant H1N2 swine virus). Characterization of rH1N1 in mice showed that this virus had higher replicability and pathogenicity than those of the seasonal human H1N1 and Eurasian avian-like swine H1N1 viruses, but was similar to the H1N1/2009 and triple-reassortant H1N2 viruses. Experiments performed on guinea pigs showed that rH1N1 was not transmissible, whereas pandemic H1N1/2009 displayed efficient transmissibility. To further determine which gene segment played a key role in transmissibility, we constructed a series of reassortants derived from rH1N1 and H1N1/2009 viruses. Direct contact transmission studies demonstrated that the HA and NS genes contributed to the transmission of H1N1/2009 virus. Second, the HA gene of H1N1/2009 virus, when combined with the H1N1/2009 NA gene, conferred efficient contact transmission among guinea pigs. The present results reveal that not only gene segment reassortment but also amino acid mutation were needed for the generation of the pandemic influenza virus.
Citation: Zhao X, Sun Y, Pu J, Fan L, Shi W, et al. (2011) Characterization of an Artificial Swine-Origin Influenza Virus with the Same Gene Combination as H1N1/2009 Virus: A Genesis Clue of Pandemic Strain. PLoS ONE 6(7): e22091. doi:10.1371/journal.pone.0022091
Editor: Todd Davis, Centers for Disease Control and Prevention, United States of America
Received: March 30, 2011; Accepted: June 14, 2011; Published: July 25, 2011
Copyright: ? 2011 Zhao et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This work was supported by the National Basic Research Program (973 Program) (No. 2011CB504702), the National Natural Science Foundation of China, the National Key Technologies R&D Program (2010BAD04B01), and the Program for Cheung Kong Scholars and Innovative Research Teams in Chinese Universities (No. IRT0866). The corresponding author was funded by Taishan Scholar Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
* E-mail: ljh@cau.edu.cn (JL); maguangpeng1977@163.com (GM)
# These authors contributed equally to this work.
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Xueli Zhao<SUP>1</SUP><SUP>#</SUP>, Yipeng Sun<SUP>1</SUP><SUP>#</SUP>, Juan Pu<SUP>1</SUP>, Lihong Fan<SUP>1</SUP>, Weimin Shi<SUP>1</SUP>, Yanxin Hu<SUP>1</SUP>, Jun Yang<SUP>1</SUP>, Qi Xu<SUP>1</SUP>, Jingjing Wang<SUP>1</SUP>, Dongjun Hou<SUP>1</SUP>, Guangpeng Ma<SUP>2</SUP><SUP>*</SUP>, Jinhua Liu<SUP>1</SUP><SUP>,</SUP><SUP>3</SUP><SUP>*</SUP>
1 Key Laboratory of Zoonosis of Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, China, 2 China Rural Technology Development Center, Beijing, China, 3 The Shandong Animal Disease Control Center, Jinan, Shandong, China
Abstract
Pandemic H1N1/2009 influenza virus, derived from a reassortment of avian, human, and swine influenza viruses, possesses a unique gene segment combination that had not been detected previously in animal and human populations. Whether such a gene combination could result in the pathogenicity and transmission as H1N1/2009 virus remains unclear. In the present study, we used reverse genetics to construct a reassortant virus (rH1N1) with the same gene combination as H1N1/2009 virus (NA and M genes from a Eurasian avian-like H1N1 swine virus and another six genes from a North American triple-reassortant H1N2 swine virus). Characterization of rH1N1 in mice showed that this virus had higher replicability and pathogenicity than those of the seasonal human H1N1 and Eurasian avian-like swine H1N1 viruses, but was similar to the H1N1/2009 and triple-reassortant H1N2 viruses. Experiments performed on guinea pigs showed that rH1N1 was not transmissible, whereas pandemic H1N1/2009 displayed efficient transmissibility. To further determine which gene segment played a key role in transmissibility, we constructed a series of reassortants derived from rH1N1 and H1N1/2009 viruses. Direct contact transmission studies demonstrated that the HA and NS genes contributed to the transmission of H1N1/2009 virus. Second, the HA gene of H1N1/2009 virus, when combined with the H1N1/2009 NA gene, conferred efficient contact transmission among guinea pigs. The present results reveal that not only gene segment reassortment but also amino acid mutation were needed for the generation of the pandemic influenza virus.
Citation: Zhao X, Sun Y, Pu J, Fan L, Shi W, et al. (2011) Characterization of an Artificial Swine-Origin Influenza Virus with the Same Gene Combination as H1N1/2009 Virus: A Genesis Clue of Pandemic Strain. PLoS ONE 6(7): e22091. doi:10.1371/journal.pone.0022091
Editor: Todd Davis, Centers for Disease Control and Prevention, United States of America
Received: March 30, 2011; Accepted: June 14, 2011; Published: July 25, 2011
Copyright: ? 2011 Zhao et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This work was supported by the National Basic Research Program (973 Program) (No. 2011CB504702), the National Natural Science Foundation of China, the National Key Technologies R&D Program (2010BAD04B01), and the Program for Cheung Kong Scholars and Innovative Research Teams in Chinese Universities (No. IRT0866). The corresponding author was funded by Taishan Scholar Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
* E-mail: ljh@cau.edu.cn (JL); maguangpeng1977@163.com (GM)
# These authors contributed equally to this work.
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