Involvement of Human Cellular Proteins and Structures in Realization of the HIV Life Cycle: A Comprehensive Review, 2024

Abstract

Human immunodeficiency virus (HIV) continues to be a global health challenge, with over 38 million people infected by the end of 2022. HIV-1, the predominant strain, primarily targets and depletes CD4+ T cells, leading to immunodeficiency and subsequent vulnerability to opportunistic infections. Despite the progress made in antiretroviral therapy (ART), drug resistance and treatment-related toxicity necessitate novel therapeutic strategies. This review delves into the intricate interplay between HIV-1 and host cellular proteins throughout the viral life cycle, highlighting key host factors that facilitate viral entry, replication, integration, and immune evasion. A focus is placed on actual findings regarding the preintegration complex, nuclear import, and the role of cellular cofactors such as FEZ1, BICD2, and NPC components in viral transport and genome integration. Additionally, the mechanisms of immune evasion via HIV-1 proteins Nef and Vpu, and their interaction with host MHC molecules and interferon signaling pathways, are explored. By examining these host-virus interactions, this review underscores the importance of host-targeted therapies in complementing ART, with a particular emphasis on the potential of genetic research and host protein stability in developing innovative treatments for HIV/AIDS.

Keywords: HIV; HIV life cycle; HIV proteins; cellular partners; human immunodeficiency virus.

Figure 1

Layout of the HIV genome based on information from the HIV Sequence Compendium 2021. Numbers indicate HXB2 coordinates.

Figure 2

Overview of the HIV life cycle based on evidence in the literature.

Figure 3

Structure and regulation of the LTR promoter. The HIV-1 LTR, indicating potential interaction sites for DNA- and RNA-binding proteins, is shown. Interactions between proteins are also shown. Green arrows mark interactions that enhance transcription. Red arrows mark interactions that inhibit transcription. Proteins circled with a solid line form a complex. Those circled with a dotted line act separately. E—enhancer, TAR—trans-activation response element, PC—preinitiation complex, EI—elongation inhibitors.