The M Segment of the 2009 Pandemic Influenza Virus Confers Increased Neuraminidase Activity, Filamentous Morphology, and Efficient Contact Transmissibility to A/Puerto Rico/8/1934-Based Reassortant Viruses

被引:82
作者
Campbell, Patricia J. [2 ]
Danzy, Shamika [1 ]
Kyriakis, Constantinos S. [1 ]
Deymier, Martin J. [3 ]
Lowen, Anice C. [1 ]
Steel, John [1 ]
机构
[1] Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA
[2] Emory Univ, Microbiol & Mol Genet Grad Program, Atlanta, GA 30322 USA
[3] Emory Univ, Yerkes Natl Primate Res Ctr, Emory Vaccine Ctr, Atlanta, GA 30322 USA
关键词
RESPIRATORY DROPLET TRANSMISSION; A VIRUS; SWINE-INFLUENZA; RECEPTOR-BINDING; MATRIX PROTEIN; GUINEA-PIG; IN-VIVO; FUNCTIONAL BALANCE; ANTIGENIC DRIFT; ION-CHANNEL;
D O I
10.1128/JVI.03607-13
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
The 2009 H1N1 lineage represented the first detection of a novel, highly transmissible influenza A virus genotype: six gene segments originated from the North American triple-reassortant swine lineage, and two segments, NA and M, derived from the Eurasian avian-like swine lineage. As neither parental lineage transmits efficiently between humans, the adaptations and mechanisms underlying the pandemic spread of the swine-origin 2009 strain are not clear. To help identify determinants of transmission, we used reverse genetics to introduce gene segments of an early pandemic isolate, A/Netherlands/602/2009 [H1N1] (NL602), into the background of A/Puerto Rico/8/1934 [H1N1] (PR8) and evaluated the resultant viruses in a guinea pig transmission model. Whereas the NL602 virus spread efficiently, the PR8 virus did not transmit. Swapping of the HA, NA, and M segments of NL602 into the PR8 background yielded a virus with indistinguishable contact transmissibility to the wild-type pandemic strain. Consistent with earlier reports, the pandemic M segment alone accounted for much of the improvement in transmission. To aid in understanding how the M segment might affect transmission, we evaluated neuraminidase activity and virion morphology of reassortant viruses. Transmission was found to correlate with higher neuraminidase activity and a more filamentous morphology. Importantly, we found that introduction of the pandemic M segment alone resulted in an increase in the neuraminidase activity of two pairs of otherwise isogenic PR8-based viruses. Thus, our data demonstrate the surprising result that functions encoded by the influenza A virus M segment impact neuraminidase activity and, perhaps through this mechanism, have a potent effect on transmissibility.
引用
收藏
页码:3802 / 3814
页数:13
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