title: The homologous tripartite viral RNA polymerase of A/swine/Korea/CT1204/2009(H1N2) influenza virus synergistically drives efficient replication and promotes respiratory droplet transmission in ferrets.
abstract: We previously reported that influenza A/swine/Korea/1204/2009(H1N2) virus was virulent and transmissible in ferrets in which the respiratory-droplet-transmissible virus (CT-Sw/1204) had acquired simultaneous hemagglutinin (HAD225G) and neuraminidase (NAS315N) mutations. Incorporating these mutations into the nonpathogenic A/swine/Korea/1130/2009(H1N2, Sw/1130) virus consequently altered pathogenicity and growth in animal models but could not establish efficient transmission or noticeable disease. We therefore exploited various reassortants of these two viruses to better understand and identify other viral factors responsible for pathogenicity, transmissibility, or both. We found that possession of the CT-Sw/1204 tripartite viral polymerase enhanced replicative ability and pathogenicity in mice more significantly than did expression of individual polymerase subunit proteins. In ferrets, homologous expression of viral RNA polymerase complex genes in the context of the mutant Sw/1130 carrying the HA225G and NA315N modifications induced optimal replication in the upper nasal and lower respiratory tracts and also promoted efficient aerosol transmission to respiratory droplet contact ferrets. These data show that the synergistic function of the tripartite polymerase gene complex of CT-Sw/1204 is critically important for virulence and transmission independent of the surface glycoproteins. Sequence comparison results reveal putative differences that are likely to be responsible for variation in disease. Our findings may help elucidate previously undefined viral factors that could expand the host range and disease severity induced by triple-reassortant swine viruses, including the A(H1N1)pdm09 virus, and therefore further justify the ongoing development of novel antiviral drugs targeting the viral polymerase complex subunits.
authors.affiliation: Department of Microbiology, College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, Republic of Korea.
authors.forename: Philippe Noriel Q
authors.initials: PN
authors.lastname: Pascua
authors.forename: Min-Suk
authors.initials: MS
authors.lastname: Song
authors.forename: Hyeok-Il
authors.initials: HI
authors.lastname: Kwon
authors.forename: Gyo-Jin
authors.initials: GJ
authors.lastname: Lim
authors.forename: Eun-Ha
authors.initials: EH
authors.lastname: Kim
authors.forename: Su-Jin
authors.initials: SJ
authors.lastname: Park
authors.forename: Ok-Jun
authors.initials: OJ
authors.lastname: Lee
authors.forename: Chul-Joong
authors.initials: CJ
authors.lastname: Kim
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Webby
authors.forename: Robert G
authors.initials: RG
authors.lastname: Webster
authors.forename: Young-Ki
authors.initials: YK
authors.lastname: Choi
mesh_terms: D000818:Animals; D001980:Bronchi / Q000166:cytology / Q000378:metabolism / Q000821:virology; D002478:Cells, Cultured; D012321:DNA-Directed RNA Polymerases / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005289:Ferrets; D016679:Genome, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000378:metabolism; D057221:Influenza A Virus, H1N2 Subtype / Q000201:enzymology / Q000254:growth & development / Q000472:pathogenicity*; D007668:Kidney / Q000166:cytology / Q000378:metabolism / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009439:Neuraminidase / Q000378:metabolism; D009976:Orthomyxoviridae Infections / Q000201:enzymology / Q000635:transmission* / Q000821:virology; D012137:Respiratory System / Q000473:pathology / Q000821:virology*; D013552:Swine; D014779:Virus Replication
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D012321:DNA-Directed RNA Polymerases; D009439:Neuraminidase