Extensive viral mimicry of 22 AIDS-related autoantigens by HIV-1 proteins and pathway analysis of 561 viral/human homologues suggest an initial treatable autoimmune component of AIDS
Extensive viral mimicry of 22 AIDS-related autoantigens by HIV-1 proteins and pathway analysis of 561 viral/human homologues suggest an initial treatable autoimmune component of AIDS
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DOI：
10.1111/j.1574-695x.2011.00848.x
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发表时间：
2011-11-01
影响因子：
--
通讯作者：
Carter, Chris J.
中科院分区：
文献类型：
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作者：
Carter, Chris J.
HIV-1病毒蛋白，特别是env蛋白，与22种艾滋病自身抗原同源，表明它们是由抗病毒抗体随后靶向人类同源物产生的。它们包括T细胞受体、CD 4和CD 95、补体成分、IgG、TNF和其他免疫相关蛋白的抗体。自身抗体可能通过敲低这些关键蛋白质而损害免疫系统，并且自身免疫攻击免疫系统本身，如在感染的早期阶段和在向AIDS转变期间的免疫激活所支持的。超过500种人类蛋白质含有与病毒肽相同的五肽或更长的肽。这种同源性解释了广泛的病毒/人相互作用组，可能与病毒同源物作为结合伴侣与人对应物竞争的能力有关。这些同源蛋白的通路分析揭示了它们参与与AIDS发病机制相关的免疫相关网络（例如，自然杀伤细胞毒性/toll、T细胞/B细胞受体信号传导/抗原加工）以及病毒和细菌进入和防御通路（吞噬体/溶酶体通路、DNA传感/NOD/RIG-1通路）。在其开始时，艾滋病可能有一个自身免疫成分选择性地针对免疫系统。免疫抑制治疗或抗体去除已经取得了一些成功，可能是治疗上有益的，特别是如果靶向通过亲和透析去除罪魁祸首抗体。
HIV-1 viral proteins, particularly the env protein, are homologous to 22 AIDS autoantigens, suggesting their creation by antiviral antibodies subsequently targeting human homologues. They include antibodies to T-cell receptors, CD4 and CD95, complement components, IgG, TNF and other immune-related proteins. Autoantibodies may compromise the immune system via knockdown of these key proteins, and autoimmune attack on the immune system itself, as supported by immune activation in early stages of infection and during the transition to AIDS. Over 500 human proteins contain pentapeptides or longer consensi, identical to viral peptides. Such homology explains the extensive viral/human interactome, likely related to the ability of viral homologues to compete with human counterparts as binding partners. Pathway analysis of these homologous proteins revealed their involvement in immune-related networks (e.g. natural killer cell toxicity/toll, T-cell/B-cell receptor signalling/antigen processing) and viral and bacterial entry and defence pathways (phagosome/lysosome pathways, DNA sensing/NOD/RIG-1 pathways) relevant to AIDS pathogenesis. At its inception, AIDS may have an autoimmune component selectively targeting the immune system. Immunosuppressive therapy or antibody removal, which has already achieved some success, might be therapeutically beneficial, particularly if targeted at removal of the culpable antibodies, via affinity dialysis.