Evolution of the M gene of the influenza A virus in different host species: large-scale sequence analysis.
Evolution of the M gene of the influenza A virus in different host species: large-scale sequence analysis.
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DOI：
10.1186/1743-422x-6-67
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发表时间：
2009-05-29
期刊：
影响因子：
4.8
通讯作者：
Oshitani H
中科院分区：
文献类型：
--
作者：
Furuse Y;Suzuki A;Kamigaki T;Oshitani H
甲型流感病毒不仅感染人类，还感染其他物种，包括禽类和猪。如果一种新型甲型流感亚型获得了在人与人之间有效传播的能力，它可能会引发下一次大流行。因此，有必要了解甲型流感病毒在不同宿主中的进化过程，以便更好地了解大流行病毒的出现。该病毒具有分段的RNA基因组，第7段M基因编码2种蛋白质。 M1是基质蛋白，M2是膜蛋白。 M基因可能参与决定宿主向性。此外，针对M1或M2蛋白以提供跨亚型保护的新型疫苗也正在开发中。我们进行本研究是为了通过分析不同物种中 M 基因的序列来研究 M 基因的进化。系统发育树揭示了物种间宿主特异性谱系和进化速率的不同。 M2 的选择压力强于M1。人流感对 M1 的选择压力强于禽流感和 M2。逐位点分析确定 M1 中的一个位点（氨基酸位置 219）在人类中被阳性选择。 M1 中的 115 和 121 位（人类和禽类之间的共有氨基酸不同）在两个宿主中都处于负选择之下。至于M2，在人类中有10个位点处于正选择状态。七个位点位于细胞外域。这可能是由于宿主的免疫压力所致。已知跨膜结构域中正选择的一个位点（位置27）与耐药性相关。并且，两个位点（位置 57 和 89）位于细胞质结构域中。这些站点涉及多种功能。甲型流感病毒的M基因是独立进化的，不同宿主对M1和M2的选择压力不同。我们发现了可能与宿主向性和免疫反应有关的潜在重要位点。这些位点可能对于不同宿主的进化过程和宿主适应很重要。
Influenza A virus infects not only humans, but also other species including avian and swine. If a novel influenza A subtype acquires the ability to spread between humans efficiently, it could cause the next pandemic. Therefore it is necessary to understand the evolutionary processes of influenza A viruses in various hosts in order to gain better knowledge about the emergence of pandemic virus. The virus has segmented RNA genome and 7th segment, M gene, encodes 2 proteins. M1 is a matrix protein and M2 is a membrane protein. The M gene may be involved in determining host tropism. Besides, novel vaccines targeting M1 or M2 protein to confer cross subtype protection have been under development. We conducted the present study to investigate the evolution of the M gene by analyzing its sequence in different species. Phylogenetic tree revealed host-specific lineages and evolution rates were different among species. Selective pressure on M2 was stronger than that on M1. Selective pressure on M1 for human influenza was stronger than that for avian influenza, as well as M2. Site-by-site analyses identified one site (amino acid position 219) in M1 as positively selected in human. Positions 115 and 121 in M1, at which consensus amino acids were different between human and avian, were under negative selection in both hosts. As to M2, 10 sites were under positive selection in human. Seven sites locate in extracellular domain. That might be due to host's immune pressure. One site (position 27) positively selected in transmembrane domain is known to be associated with drug resistance. And, two sites (positions 57 and 89) locate in cytoplasmic domain. The sites are involved in several functions. The M gene of influenza A virus has evolved independently, under different selective pressure on M1 and M2 among different hosts. We found potentially important sites that may be related to host tropism and immune responses. These sites may be important for evolutional process in different hosts and host adaptation.