Tang Julian W, Ngai Karry L K, Lam Wai Y, Chan Paul K S
Department of Microbiology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong Special Administrative Region, China.
PLoS One. 2008 Jul 23;3(7):e2768. doi: 10.1371/journal.pone.0002768.
The underlying basis for the seasonality of influenza A viruses is still uncertain. Phylogenetic studies investigated this phenomenon but have lacked sequences from more subtropical and tropical regions, particularly from Southeast Asia.
METHODOLOGY/PRINCIPAL FINDINGS: 281 complete hemagglutinin (HA) and neuraminidase (NA) sequences were obtained from influenza A(H3N2) viruses, collected over 10 years (1997-2006) from Hong Kong. These dated sequences were analyzed with influenza A(H3N2) vaccine strain sequences (Syd/5/97, Mos/10/99, Fuj/411/02, Cal/7/04) and 315 other publicly available dated sequences from elsewhere, worldwide. In addition, the NA sequence alignment was inspected for the presence of any naturally occurring, known, neuraminidase inhibitor (NAI) resistance-associated amino acid mutations (R292K and E119V). Before 2001, the Hong Kong HA and NA sequences clustered more closely with the older vaccine sequences (Syd/5/97, Mos/10/99) than did sequences from elsewhere. After 2001, this trend reversed with significant clusters containing HA and NA sequences from different locations, isolated at different times, suggesting that viral migration may account for much of the influenza A(H3N2) seasonality during this 10-year period. However, at least one example from Hong Kong was found suggesting that in some years, influenza A(H3N2) viruses may persist in the same location, perhaps continuing to circulate, sub-clinically, at low levels between seasons, to re-emerge in the influenza season the following year, relatively unchanged. None of these Hong Kong influenza A(H3N2) NA sequences contained any of the known NAI-resistance associated mutations.
CONCLUSIONS/SIGNIFICANCE: The seasonality of influenza A(H3N2) may be largely due to global migration, with similar viruses appearing in different countries at different times. However, occasionally, some viruses may remain within a single location and continue to circulate within that population, to re-emerge during the next influenza season, with relatively little genetic change. Naturally occurring NAI resistance mutations were absent or, at least, very rare in this population.
甲型流感病毒季节性变化的潜在基础仍不明确。系统发育研究对这一现象进行了调查，但缺乏来自更多亚热带和热带地区，特别是东南亚地区的序列。
方法/主要发现：从1997年至2006年的10年间收集自香港的甲型流感病毒（H3N2）中获得了281条完整的血凝素（HA）和神经氨酸酶（NA）序列。将这些有时间标记的序列与甲型流感病毒（H3N2）疫苗株序列（悉尼/5/97、莫斯科/10/99、富士/411/02、加利福尼亚/7/04）以及全球其他地方公开可得的315条有时间标记的序列进行分析。此外，检查NA序列比对中是否存在任何自然发生的、已知的与神经氨酸酶抑制剂（NAI）耐药相关的氨基酸突变（R292K和E119V）。2001年之前，香港的HA和NA序列比其他地方的序列与更早的疫苗序列（悉尼/5/97、莫斯科/10/99）聚类更紧密。2001年之后，这种趋势发生逆转，出现了包含来自不同地点、在不同时间分离的HA和NA序列的显著聚类，这表明病毒迁移可能是这10年期间甲型流感病毒（H3N2）季节性变化的主要原因。然而，发现至少有一个来自香港的例子表明，在某些年份，甲型流感病毒（H3N2）可能在同一地点持续存在，可能在季节间以低水平在亚临床状态下继续传播，次年在流感季节再次出现，相对没有变化。这些香港甲型流感病毒（H3N2）的NA序列均未包含任何已知的与NAI耐药相关的突变。
结论/意义：甲型流感病毒（H3N2）的季节性变化可能主要归因于全球迁移，类似的病毒在不同时间出现在不同国家。然而，偶尔有些病毒可能会留在单一地点并在该人群中继续传播，在下一个流感季节再次出现，基因变化相对较小。在这一人群中不存在自然发生的NAI耐药突变，或者至少非常罕见。
