The 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.