The Immune Escape Strategy of Rabies Virus and Its Pathogenicity Mechanisms.

IF 3.8 3区 医学 Q2 VIROLOGY Viruses-Basel Pub Date : 2024-11-14 DOI:10.3390/v16111774
Abraha Bahlbi Kiflu
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Abstract

In contrast to most other rhabdoviruses, which spread by insect vectors, the rabies virus (RABV) is a very unusual member of the Rhabdoviridae family, since it has evolved to be fully adapted to warm-blooded hosts and spread directly between them. There are differences in the immune responses to laboratory-attenuated RABV and wild-type rabies virus infections. Various investigations showed that whilst laboratory-attenuated RABV elicits an innate immune response, wild-type RABV evades detection. Pathogenic RABV infection bypasses immune response by antagonizing interferon induction, which prevents downstream signal activation and impairs antiviral proteins and inflammatory cytokines production that could eliminate the virus. On the contrary, non-pathogenic RABV infection leads to immune activation and suppresses the disease. Apart from that, through recruiting leukocytes into the central nervous system (CNS) and enhancing the blood-brain barrier (BBB) permeability, which are vital factors for viral clearance and protection, cytokines/chemokines released during RABV infection play a critical role in suppressing the disease. Furthermore, early apoptosis of neural cells limit replication and spread of avirulent RABV infection, but street RABV strains infection cause delayed apoptosis that help them spread further to healthy cells and circumvent early immune exposure. Similarly, a cellular regulation mechanism called autophagy eliminates unused or damaged cytoplasmic materials and destroy microbes by delivering them to the lysosomes as part of a nonspecific immune defense mechanism. Infection with laboratory fixed RABV strains lead to complete autophagy and the viruses are eliminated. But incomplete autophagy during pathogenic RABV infection failed to destroy the viruses and might aid the virus in dodging detection by antigen-presenting cells, which could otherwise elicit adaptive immune activation. Pathogenic RABV P and M proteins, as well as high concentration of nitric oxide, which is produced during rabies virus infection, inhibits activities of mitochondrial proteins, which triggers the generation of reactive oxygen species, resulting in oxidative stress, contributing to mitochondrial malfunction and, finally, neuron process degeneration.

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狂犬病病毒的免疫逃逸策略及其致病机制
与通过昆虫媒介传播的大多数其他狂犬病病毒相比,狂犬病病毒(RABV)是狂犬病病毒科中一个非常不寻常的成员,因为它在进化过程中完全适应了温血宿主,并直接在温血宿主之间传播。实验室减毒狂犬病病毒和野生型狂犬病病毒感染的免疫反应存在差异。各种研究表明,实验室减毒狂犬病病毒会引起先天性免疫反应,而野生型狂犬病病毒则会逃避检测。致病性 RABV 感染可通过拮抗干扰素诱导来绕过免疫反应,从而阻止下游信号的激活,并损害可消除病毒的抗病毒蛋白和炎症细胞因子的产生。相反,非致病性 RABV 感染会导致免疫激活并抑制疾病。此外,RABV 感染期间释放的细胞因子/趋化因子通过招募白细胞进入中枢神经系统(CNS)和增强血脑屏障(BBB)的通透性(这些都是清除和保护病毒的重要因素),在抑制疾病方面发挥了关键作用。此外,神经细胞的早期凋亡限制了无毒 RABV 感染的复制和扩散,但街头 RABV 株感染会导致延迟凋亡,这有助于它们进一步扩散到健康细胞,并规避早期免疫暴露。同样,作为非特异性免疫防御机制的一部分,一种名为自噬的细胞调节机制可消除未使用或受损的细胞质物质,并通过将微生物送入溶酶体来消灭它们。感染实验室固定的 RABV 毒株会导致完全的自噬,病毒被消灭。但在致病性 RABV 感染过程中,不完全的自噬未能消灭病毒,反而可能帮助病毒躲避抗原递呈细胞的检测,否则会引起适应性免疫激活。致病性 RABV P 蛋白和 M 蛋白以及狂犬病病毒感染时产生的高浓度一氧化氮抑制了线粒体蛋白的活动,从而引发活性氧的产生,导致氧化应激,造成线粒体功能失调,最终导致神经元过程退化。
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来源期刊
Viruses-Basel
Viruses-Basel VIROLOGY-
CiteScore
7.30
自引率
12.80%
发文量
2445
审稿时长
1 months
期刊介绍: Viruses (ISSN 1999-4915) is an open access journal which provides an advanced forum for studies of viruses. It publishes reviews, regular research papers, communications, conference reports and short notes. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced. We also encourage the publication of timely reviews and commentaries on topics of interest to the virology community and feature highlights from the virology literature in the ''News and Views'' section. Electronic files or software regarding the full details of the calculation and experimental procedure, if unable to be published in a normal way, can be deposited as supplementary material.
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