HIV Genome-Wide Protein Associations: a Review of 30 Years of Research

Abstract

SUMMARYThe HIV genome encodes a small number of viral proteins (i.e., 16), invariably establishing cooperative associations among HIV proteins and between HIV and host proteins, to invade host cells and hijack their internal machineries. As a known example, the HIV envelope glycoprotein GP120 is closely associated with GP41 for viral entry. From a genome-wide perspective, a hypothesis can be worked out to determine whether 16 HIV proteins could develop 120 possible pairwise associations either by physical interactions or by functional associations mediated via HIV or host molecules. Here, we present the first systematic review of experimental evidence on HIV genome-wide protein associations using a large body of publications accumulated over the past 3 decades. Of 120 possible pairwise associations between 16 HIV proteins, at least 34 physical interactions and 17 functional associations have been identified. To achieve efficient viral replication and infection, HIV protein associations play essential roles (e.g., cleavage, inhibition, and activation) during the HIV life cycle. In either a dispensable or an indispensable manner, each HIV protein collaborates with another viral protein to accomplish specific activities that precisely take place at the proper stages of the HIV life cycle. In addition, HIV genome-wide protein associations have an impact on anti-HIV inhibitors due to the extensive cross talk between drug-inhibited proteins and other HIV proteins. Overall, this study presents for the first time a comprehensive overview of HIV genome-wide protein associations, highlighting meticulous collaborations between all viral proteins during the HIV life cycle.

Assessing diversity in multiplex networks

“…It is possible to see that the pair 2 and 16 brings the 41% of the global diversity and layer 6 is the less The node with the highest diversity value, gag, is the main structural precursor protein of HIV-1, which will be processed into four smaller polypeptides with differential functions, from interaction to the lipid cell membrane, interactions with other proteins, RNA binding and activator of the protease and reverse transcriptase functions. Gag has both early and late roles during the HIV-1 life cycle, from capsid assembly and disassembly, envelope protein binding and stabilization, virion maturation after particle release, and early post-entry steps in virus reverse transcription [46][47][48][49][50][51]. In a recent work [47], the gag protein also played an important role in how HIV hacks cells to propagate itself.…”

Tat basic domain: A “Swiss army knife” of HIV‐1 Tat?

“…Presence of independent sites for nuclear entry and nucleolar accumulation might be evolutionarily unfavorable for Tat. Indeed, HIV‐1 genome itself is just under 10 kb with 16 proteins successfully serving its biology . Both nuclear and nucleolar accumulation could be achieved by Tat binding to/associating with other nuclear/nucleolar proteins or RNAs through its highly charged basic domain.…”

Recent 5-Year Findings and Technological Advances in the Proteomic Study of HIV-Associated Disorders

“…HIV depends mainly on host factors to complete its life cycle [58]. Identification of the host factors employed by HIV is very useful for understanding the viral invasion and host defense strategies.…”