A comparative analysis of host responses to avian influenza infection in ducks and chickens highlights a role for the interferon-induced transmembrane proteins in viral resistance.
A comparative analysis of host responses to avian influenza infection in ducks and chickens highlights a role for the interferon-induced transmembrane proteins in viral resistance.
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DOI：
10.1186/s12864-015-1778-8
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发表时间：
2015-08-04
期刊：
影响因子：
4.4
通讯作者：
Burt DW
中科院分区：
文献类型：
--
作者：
Smith J;Smith N;Yu L;Paton IR;Gutowska MW;Forrest HL;Danner AF;Seiler JP;Digard P;Webster RG;Burt DW
鸡只易感染有限数量的甲型流感病毒，是人类流感大流行的潜在来源。特别地，H5和H7血凝素亚型可以在鸡科家禽中从低致病性菌株进化到高致病性菌株。另一方面，鸭子是这些病毒的天然宿主，能够抵御大多数禽流感病毒株。对感染高致病性（H5 N1）和低致病性（H5 N2）流感病毒的鸟类的肺和回肠组织样本进行转录组测序，使我们能够比较这两个物种对这些感染的早期宿主反应。鸡（但不是鸭）缺乏病毒ssRNA的细胞内受体RIG-I和重要的RIG-I结合蛋白RNF 135的基因。这些基因含量的差异部分解释了鸡和鸭对低致病性和高致病性禽流感病毒的宿主反应差异。我们揭示了非常不同的模式的干扰素诱导的跨膜蛋白（IFITM）基因家族的成员在鸭和鸡的表达。在鸭子中，IFITM 1、2和3在对高致病性禽流感的反应中强烈上调，而在鸡中几乎没有观察到反应。基因表达谱的聚类表明IFITM 1和2具有抗病毒反应，IFITM 3可能通过细胞膜融合抑制禽流感病毒。我们还表明，通过分子系统发育分析，禽IFITM 1和IFITM 3基因已受到情节和普遍的积极选择在特定的密码子。特别是，禽IFITM 1在已知限制流感病毒感染的位点显示出鸭谱系中的正选择的证据。总之，这些结果支持了一个模型，其中IFITM 123蛋白家族和RIG-I在鸭对高致病性和低致病性禽流感病毒株的耐受性中与鸡相比都起着至关重要的作用。本文的在线版本（doi：10.1186/s12864-015-1778-8）包含补充材料，可供授权用户使用。
Chickens are susceptible to infection with a limited number of Influenza A viruses and are a potential source of a human influenza pandemic. In particular, H5 and H7 haemagglutinin subtypes can evolve from low to highly pathogenic strains in gallinaceous poultry. Ducks on the other hand are a natural reservoir for these viruses and are able to withstand most avian influenza strains. Transcriptomic sequencing of lung and ileum tissue samples from birds infected with high (H5N1) and low (H5N2) pathogenic influenza viruses has allowed us to compare the early host response to these infections in both these species. Chickens (but not ducks) lack the intracellular receptor for viral ssRNA, RIG-I and the gene for an important RIG-I binding protein, RNF135. These differences in gene content partly explain the differences in host responses to low pathogenic and highly pathogenic avian influenza virus in chicken and ducks. We reveal very different patterns of expression of members of the interferon-induced transmembrane protein (IFITM) gene family in ducks and chickens. In ducks, IFITM1, 2 and 3 are strongly up regulated in response to highly pathogenic avian influenza, where little response is seen in chickens. Clustering of gene expression profiles suggests IFITM1 and 2 have an anti-viral response and IFITM3 may restrict avian influenza virus through cell membrane fusion. We also show, through molecular phylogenetic analyses, that avian IFITM1 and IFITM3 genes have been subject to both episodic and pervasive positive selection at specific codons. In particular, avian IFITM1 showed evidence of positive selection in the duck lineage at sites known to restrict influenza virus infection. Taken together these results support a model where the IFITM123 protein family and RIG-I all play a crucial role in the tolerance of ducks to highly pathogenic and low pathogenic strains of avian influenza viruses when compared to the chicken. The online version of this article (doi:10.1186/s12864-015-1778-8) contains supplementary material, which is available to authorized users.