Mapping the interaction sites of Influenza A viruses and human complement Factor H
Mapping the interaction sites of Influenza A viruses and human complement Factor H
复制标题
绘制甲型流感病毒与人类补体 H 因子的相互作用位点图谱
DOI：
10.1101/2023.09.15.557969
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Rabeeah I
中科院分区：
文献类型：
--
作者：
Rabeeah I
补体系统是抵抗微生物感染的先天免疫机制。它涉及通过经典途径、凝集素途径和替代途径激活的效应分子级联。因此，许多病原体结合或并入其结构宿主补体途径的负调节物作为逃避机制。因子H（FH）是补体旁路途径的负调节剂，其保护宿主的“自身”细胞免受非特异性补体攻击。包括人甲型流感病毒（IAV）在内的病毒已显示与FH结合。在这里，我们表明，IAV的人和禽源可以直接结合到人FH和相互作用是通过IAV表面糖蛋白血凝素（HA）介导的。HA结合到FH结构、补体控制蛋白模块、CCP 5-7和CCP 15-20上的常见病原体结合足迹。FH与H1和H3的结合表明，相互作用与两种HA的受体结合位点重叠，但H3 HA的足迹比H1 HA更广泛。HA - FH相互作用阻碍了H1N1和H3 N2 IAV毒株的初始进入，但其对病毒在人肺细胞中的多拷贝复制的影响具有毒株特异性。FH预孵育可显著抑制H3 N2病毒与细胞的结合，而对人H1N1或禽H9 N2和H5 N3 IAV株的复制率和子代病毒释放没有改变。我们已经绘制了IAV和FH之间的相互作用，其对病毒或宿主的意义尚待阐明。
The complement system is an innate immune mechanism against microbial infection. It involves a cascade of effector molecules that is activated via classical, lectin and alternative pathways. Consequently, many pathogens bind to or incorporate in their structures host negative regulators of the complement pathways as an evasion mechanism. Factor H (FH) is a negative regulator of the complement alternative pathway that protects “self” cells of the host from non-specific complement attack. Viruses including human influenza A viruses (IAVs) have been shown to bind to FH. Here we show that IAVs of both human and avian origin can bind directly to human FH and the interaction is mediated via the IAV surface glycoprotein haemagglutinin (HA). HA bound to common pathogen binding footprints on the FH structure, complement control protein modules, CCP 5-7 and CCP 15-20. The FH binding to H1 and H3 showed that the interaction overlapped with the receptor binding site of both HAs but the footprint was more extensive for the H3 HA than the H1 HA. The HA - FH interaction impeded the initial entry of H1N1 and H3N2 IAV strains but its impact on viral multicycle replication in human lung cells was strain specific. The H3N2 virus binding to cells was significantly inhibited by preincubation with FH, whereas there was no alteration in replicative rate and progeny virus release for human H1N1 or avian H9N2 and H5N3 IAV strains. We have mapped the interaction between IAV and FH, the significance of which for the virus or host is yet to be elucidated.
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影响因子：
7.3
作者：
Józsi M
通讯作者：
Józsi M
补体因子 H 的纯化、定量和功能分析。
影响因子：
--
作者：
Bing;B. Moffatt;M. Fedorova;Claire Villiers;J. N. Arnold;Eugenie Du;Astrid Swinkels;Man Li;A. Ryan;Robert B Sim
通讯作者：
Robert B Sim
影响因子：
3.6
作者：
Ferreira VP;Pangburn MK;Cortés C
通讯作者：
Cortés C
1 型单纯疱疹病毒的糖蛋白 C 对于病毒逃避不依赖于抗体的补体介导的病毒灭活和病毒感染细胞的裂解至关重要。
影响因子：
3.8
作者：
Y. Hidaka;Y. Sakai;Y. Toh;R. Mori
通讯作者：
R. Mori
正常人血清中和流感病毒：涉及抗体和补体的机制。
DOI：
--
发表时间：
1983
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Beebe,DP;Schreiber,RD;Cooper,NR
通讯作者：
Cooper,NR