Variations in the hemagglutinin of the 2009 H1N1 pandemic virus: potential for strains with altered virulence phenotype?
Variations in the hemagglutinin of the 2009 H1N1 pandemic virus: potential for strains with altered virulence phenotype?
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DOI：
10.1371/journal.ppat.1001145
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发表时间：
2010-10-14
期刊：
影响因子：
6.7
通讯作者：
Perez DR
中科院分区：
文献类型：
--
作者：
Ye J;Sorrell EM;Cai Y;Shao H;Xu K;Pena L;Hickman D;Song H;Angel M;Medina RA;Manicassamy B;Garcia-Sastre A;Perez DR
A novel, swine-origin influenza H1N1 virus (H1N1pdm) caused the first pandemic of the 21st century. This pandemic, although efficient in transmission, is mild in virulence. This atypical mild pandemic season has raised concerns regarding the potential of this virus to acquire additional virulence markers either through further adaptation or possibly by immune pressure in the human host. Using the mouse model we generated, within a single round of infection with A/California/04/09/H1N1 (Ca/04), a virus lethal in mice—herein referred to as mouse-adapted Ca/04 (ma-Ca/04). Five amino acid substitutions were found in the genome of ma-Ca/04: 3 in HA (D131E, S186P and A198E), 1 in PA (E298K) and 1 in NP (D101G). Reverse genetics analyses of these mutations indicate that all five mutations from ma-Ca/04 contributed to the lethal phenotype; however, the D131E and S186P mutations—which are also found in the 1918 and seasonal H1N1 viruses—in HA alone were sufficient to confer virulence of Ca/04 in mice. HI assays against H1N1pdm demonstrate that the D131E and S186P mutations caused minor antigenic changes and, likely, affected receptor binding. The rapid selection of ma-Ca/04 in mice suggests that a virus containing this constellation of amino acids might have already been present in Ca/04, likely as minor quasispecies. The 19th century experienced three major influenza pandemics: the Spanish flu of 1918 (H1N1), the Asian flu of 1957 (H2N2) and the Hong Kong flu of 1968 (H3N2). These pandemics were introduced into the human population through the accumulation of avian and human influenza genes (genetic reassortment), creating with each pandemic a novel influenza virus, one that the human population had not been exposed to. These pandemics were associated with high morbidity and mortality; the 1918 pandemic was responsible for an estimated 40 million deaths. In April 2009, a novel, swine-origin influenza H1N1 virus (H1N1pdm) caused the first influenza pandemic of the 21st century. This pandemic was a result of genetic reassortment between not only human and avian influenza genes, but also swine influenza genes. This H1N1 pandemic, although efficient in human-to-human transmission, differed greatly from the previous pandemics in its mild virulence. This atypical mild pandemic season has raised concerns regarding the potential of this virus to become more virulent. Using a mouse model, we were able to demonstrate that this pandemic strain is amenable to mutations that lead to a more virulent virus.
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影响因子：
2.3
作者：
Lyon, Jane B.;Remigio, Cheryl;Deline, Carol
通讯作者：
Deline, Carol
影响因子：
3.7
作者：
Igarashi M;Ito K;Yoshida R;Tomabechi D;Kida H;Takada A
通讯作者：
Takada A
DOI：
10.1136/bmj.b5213
发表时间：
2009-12-10
期刊：
BMJ (Clinical research ed.)
影响因子：
--
作者：
Donaldson LJ;Rutter PD;Ellis BM;Greaves FE;Mytton OT;Pebody RG;Yardley IE
通讯作者：
Yardley IE
影响因子：
56.9
作者：
Gamblin, SJ;Haire, LF;Skehel, JJ
通讯作者：
Skehel, JJ
影响因子：
1.6
作者：
Al Hajjar S;McIntosh K
通讯作者：
McIntosh K