tetano
Editor, Senior Moderator
J Virol. 2013 Jul 17. [Epub ahead of print]
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.
Pascua PN, Song MS, Kwon HI, Lim GJ, Kim EH, Park SJ, Lee OJ, Kim CJ, Webby RJ, Webster RG, Choi YK.
Source
Department of Microbiology, College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju 361-763, Republic of Korea.
Abstract
We previously reported that 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 HAD225G and NAS315N mutations. Incorporating these mutations into the non-pathogenic A/swine/Korea/1130/2009(H1N2, Sw/1130) virus consequently altered pathogenicity and growth in animal models but could not establish efficient transmission or remarkable 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 individual expression of 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.
PMID:
23864624
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23864624
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.
Pascua PN, Song MS, Kwon HI, Lim GJ, Kim EH, Park SJ, Lee OJ, Kim CJ, Webby RJ, Webster RG, Choi YK.
Source
Department of Microbiology, College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju 361-763, Republic of Korea.
Abstract
We previously reported that 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 HAD225G and NAS315N mutations. Incorporating these mutations into the non-pathogenic A/swine/Korea/1130/2009(H1N2, Sw/1130) virus consequently altered pathogenicity and growth in animal models but could not establish efficient transmission or remarkable 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 individual expression of 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.
PMID:
23864624
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23864624