Viral Disease Biology, Department of Pathogen Biology, Rajiv Gandhi Center for Biotechnology, Thiruvananthapuram, India.
Manipal Academy of Higher Education, Manipal, India.
Front Immunol. 2020 Sep 29;11:573583. doi: 10.3389/fimmu.2020.573583. eCollection 2020.
Complement, a part of the innate arm of the immune system, is integral to the frontline defense of the host against innumerable pathogens, which includes RNA viruses. Among the major groups of viruses, RNA viruses contribute significantly to the global mortality and morbidity index associated with viral infection. Despite multiple routes of entry adopted by these viruses, facing complement is inevitable. The initial interaction with complement and the nature of this interaction play an important role in determining host resistance versus susceptibility to the viral infection. Many RNA viruses are potent activators of complement, often resulting in virus neutralization. Yet, another facet of virus-induced activation is the exacerbation in pathogenesis contributing to the overall morbidity. The severity in disease and death associated with RNA virus infections shows a tip in the scale favoring viruses. Growing evidence suggest that like their DNA counterparts, RNA viruses have co-evolved to master ingenious strategies to remarkably restrict complement. Modulation of host genes involved in antiviral responses contributed prominently to the adoption of unique strategies to keep complement at bay, which included either down regulation of activation components (C3, C4) or up regulation of complement regulatory proteins. All this hints at a possible "hijacking" of the cross-talk mechanism of the host immune system. Enveloped RNA viruses have a selective advantage of not only modulating the host responses but also recruiting membrane-associated regulators of complement activation (RCAs). This review aims to highlight the significant progress in the understanding of RNA virus-complement interactions.
补体是先天免疫系统的一部分，对于宿主抵御无数病原体（包括 RNA 病毒）的一线防御至关重要。在主要的病毒群体中，RNA 病毒在与病毒感染相关的全球死亡率和发病率指数方面做出了重大贡献。尽管这些病毒采用了多种进入途径，但它们都不可避免地会遇到补体。补体的初始相互作用及其性质在决定宿主对病毒感染的抵抗力或易感性方面起着重要作用。许多 RNA 病毒是补体的有效激活剂，常常导致病毒中和。然而，病毒诱导激活的另一个方面是导致发病机制恶化，从而导致整体发病率增加。与 RNA 病毒感染相关的疾病严重程度和死亡率显示出有利于病毒的天平倾斜。越来越多的证据表明，与它们的 DNA 对应物一样，RNA 病毒已经共同进化出巧妙的策略来显著限制补体。参与抗病毒反应的宿主基因的调节对采用独特的策略来阻止补体发挥了重要作用，包括下调激活成分（C3、C4）或上调补体调节蛋白。所有这些都暗示着宿主免疫系统的交叉对话机制可能被“劫持”。包膜 RNA 病毒具有选择性优势，不仅可以调节宿主反应，还可以招募补体激活的膜相关调节剂（RCAs）。本综述旨在强调理解 RNA 病毒-补体相互作用方面的显著进展。
