Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne VIC 3000, Australia.
Roche Pharma Research and Early Development, Roche Innovation Center Basel, 4070 Basel, Switzerland.
Viruses. 2020 Dec 2;12(12):1381. doi: 10.3390/v12121381.
The paramyxo- and pneumovirus family includes a wide range of viruses that can cause respiratory and/or systemic infections in humans and animals. The significant disease burden of these viruses is further exacerbated by the limited therapeutics that are currently available. Host cellular proteins that can antagonize or limit virus replication are therefore a promising area of research to identify candidate molecules with the potential for host-targeted therapies. Host proteins known as host cell restriction factors are constitutively expressed and/or induced in response to virus infection and include proteins from interferon-stimulated genes (ISGs). Many ISG proteins have been identified but relatively few have been characterized in detail and most studies have focused on studying their antiviral activities against particular viruses, such as influenza A viruses and human immunodeficiency virus (HIV)-1. This review summarizes current literature regarding host cell restriction factors against paramyxo- and pneumoviruses, on which there is more limited data. Alongside discussion of known restriction factors, this review also considers viral countermeasures in overcoming host restriction, the strengths and limitations in different experimental approaches in studies reported to date, and the challenges in reconciling differences between in vitro and in vivo data. Furthermore, this review provides an outlook regarding the landscape of emerging technologies and tools available to study host cell restriction factors, as well as the suitability of these proteins as targets for broad-spectrum antiviral therapeutics.
副黏病毒和肺病毒家族包括多种可导致人类和动物呼吸道和/或全身感染的病毒。由于目前可用的治疗方法有限，这些病毒的重大疾病负担进一步加重。因此，拮抗或限制病毒复制的宿主细胞蛋白是一个很有前途的研究领域，可以确定具有宿主靶向治疗潜力的候选分子。宿主细胞限制因子是一类固有表达和/或在病毒感染时被诱导表达的宿主蛋白，包括干扰素刺激基因（ISG）的蛋白。已经鉴定出许多 ISG 蛋白，但对其进行详细描述的相对较少，大多数研究都集中在研究它们针对特定病毒（如甲型流感病毒和人类免疫缺陷病毒 1 型）的抗病毒活性。这篇综述总结了有关针对副黏病毒和肺病毒的宿主细胞限制因子的现有文献，关于这些因子的数据更为有限。除了讨论已知的限制因子外，本综述还考虑了病毒对抗宿主限制的对策、迄今为止报道的研究中不同实验方法的优缺点，以及调和体外和体内数据差异的挑战。此外，本综述还展望了研究宿主细胞限制因子的新兴技术和工具的应用前景，以及这些蛋白作为广谱抗病毒治疗靶点的适用性。
