Division of Virology, Indian Council of Medical Research National Institute of Cholera and Enteric Diseases, Kolkata, India.
Institute of Biochemistry II, Faculty of Medicine, Goethe University, Frankfurt, Germany.
Front Cell Infect Microbiol. 2022 Sep 14;12:977799. doi: 10.3389/fcimb.2022.977799. eCollection 2022.
The biology of the viral life cycle essentially includes two structural and functional entities-the viral genome and protein machinery constituting the viral arsenal and an array of host cellular components which the virus closely associates with-to ensure successful perpetuation. The obligatory requirements of the virus to selectively evade specific host cellular factors while exploiting certain others have been immensely important to provide the platform for designing host-directed antiviral therapeutics. Although the spectrum of host-virus interaction is multifaceted, host factors that particularly influence viral replication have immense therapeutic importance. During lytic proliferation, viruses usually form replication factories which are specialized subcellular structures made up of viral proteins and replicating nucleic acids. These viral niches remain distinct from the rest of the cellular milieu, but they effectively allow spatial proximity to selective host determinants. Here, we will focus on the interaction between the replication compartments of a double stranded RNA virus rotavirus (RV) and the host cellular determinants of infection. RV, a diarrheagenic virus infecting young animals and children, forms replication bodies termed viroplasms within the host cell cytoplasm. Importantly, viroplasms also serve as the site for transcription and early morphogenesis of RVs and are very dynamic in nature. Despite advances in the understanding of RV components that constitute the viroplasmic architecture, knowledge of the contribution of host determinants to viroplasm dynamicity has remained limited. Emerging evidence suggests that selective host determinants are sequestered inside or translocated adjacent to the RV viroplasms. Functional implications of such host cellular reprogramming are also ramifying-disarming the antiviral host determinants and usurping the pro-viral components to facilitate specific stages of the viral life cycle. Here, we will provide a critical update on the wide variety of host cellular pathways that have been reported to regulate the spatial and temporal dynamicity of RV viroplasms. We will also discuss the methods used so far to study the host-viroplasm interactions and emphasize on the potential host factors which can be targeted for therapeutic intervention in the future.
病毒生命周期的生物学本质包括两个结构和功能实体——构成病毒武器库的病毒基因组和蛋白机制,以及病毒密切关联的一系列宿主细胞成分——以确保成功延续。病毒选择性逃避特定宿主细胞因子,同时利用某些其他因子的强制性要求,对于设计宿主定向抗病毒治疗药物提供了重要平台。尽管宿主-病毒相互作用的范围很广,但特别影响病毒复制的宿主因素具有巨大的治疗意义。在裂解增殖过程中,病毒通常形成复制工厂,这是由病毒蛋白和复制核酸组成的专门亚细胞结构。这些病毒小生境与细胞环境的其余部分明显不同,但它们有效地允许空间接近选择性宿主决定因素。在这里,我们将重点关注双链 RNA 病毒轮状病毒 (RV) 的复制隔间与宿主细胞感染决定因素之间的相互作用。RV 是一种感染幼小动物和儿童的腹泻病毒,它在宿主细胞质内形成称为病毒质的复制体。重要的是,病毒质也是 RV 转录和早期形态发生的场所,其性质非常动态。尽管对构成病毒质结构的 RV 成分的理解有所进展,但对宿主决定因素对病毒质动态性的贡献的了解仍然有限。新出现的证据表明,选择性宿主决定因素被隔离在 RV 病毒质内或易位到其附近。这种宿主细胞重编程的功能影响也在扩散——消除抗病毒宿主决定因素,并利用促病毒成分来促进病毒生命周期的特定阶段。在这里,我们将提供一个关于广泛的宿主细胞途径的批判性更新,这些途径已被报道可调节 RV 病毒质的时空动态性。我们还将讨论迄今为止用于研究宿主-病毒质相互作用的方法,并强调未来可以作为治疗干预目标的潜在宿主因素。