Human TRIM5?: Autophagy Connects Cell-Intrinsic HIV-1 Restriction and Innate Immune Sensor Functioning.

ABSTRACT: Human immunodeficiency virus-1 (HIV-1) persists as a global health concern, with an incidence rate of approximately 2 million, and estimated global prevalence of over 35 million. Combination antiretroviral treatment is highly effective, but HIV-1 patients that have been treated still suffer from chronic inflammation and residual viral replication. It is therefore paramount to identify therapeutically efficacious strategies to eradicate viral reservoirs and ultimately develop a cure for HIV-1. It has been long accepted that the restriction factor tripartite motif protein 5 isoform alpha (TRIM5?) restricts HIV-1 infection in a species-specific manner, with rhesus macaque TRIM5? strongly restricting HIV-1, and human TRIM5? having a minimal restriction capacity. However, several recent studies underscore human TRIM5? as a cell-dependent HIV-1 restriction factor. Here, we present an overview of the latest research on human TRIM5? and propose a novel conceptualization of TRIM5? as a restriction factor with a varied portfolio of antiviral functions, including mediating HIV-1 degradation through autophagy- and proteasome-mediated mechanisms, and acting as a viral sensor and effector of antiviral signaling. We have also expanded on the protective antiviral roles of autophagy and outline the therapeutic potential of autophagy modulation to intervene in chronic HIV-1 infection.

SUBMITTER: Cloherty APM 

PROVIDER: S-EPMC7923229 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature