title: Characterization of an artificial swine-origin influenza virus with the same gene combination as H1N1/2009 virus: a genesis clue of pandemic strain.
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.
authors.affiliation: Key Laboratory of Zoonosis of Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors.forename: Xueli
authors.initials: X
authors.lastname: Zhao
authors.forename: Yipeng
authors.initials: Y
authors.lastname: Sun
authors.forename: Juan
authors.initials: J
authors.lastname: Pu
authors.forename: Lihong
authors.initials: L
authors.lastname: Fan
authors.forename: Weimin
authors.initials: W
authors.lastname: Shi
authors.forename: Yanxin
authors.initials: Y
authors.lastname: Hu
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.forename: Qi
authors.initials: Q
authors.lastname: Xu
authors.forename: Jingjing
authors.initials: J
authors.lastname: Wang
authors.forename: Dongjun
authors.initials: D
authors.lastname: Hou
authors.forename: Guangpeng
authors.initials: G
authors.lastname: Ma
authors.forename: Jinhua
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D005260:Female; D005814:Genes, Viral / Q000235:genetics*; D006168:Guinea Pigs; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000235:genetics; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics* / Q000472:pathogenicity; D057221:Influenza A Virus, H1N2 Subtype / Q000235:genetics; D007251:Influenza, Human / Q000453:epidemiology* / Q000473:pathology / Q000635:transmission / Q000821:virology*; D051379:Mice; D058873:Pandemics; D016865:Reassortant Viruses / Q000235:genetics* / Q000472:pathogenicity; D059386:Reverse Genetics; D013552:Swine; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000235:genetics
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; C108309:NS protein, influenza virus; D017361:Viral Nonstructural Proteins