HIV-1 Exploits the Host Factor RuvB-like 2 to Balance Viral Protein Expression

• RVB2 inhibits HIV-1 Gag expression in a matrix (MA)-dependent manner
• RVB2 interacts with MA and the translating mRNA and promotes RNA degradation
• HIV-1-encoded envelope protein antagonizes RVB2 by competitive interaction with MA
• HIV-1 makes use of RVB2 for efficient production of infectious virion particles

SummaryThe correct ratio of the HIV-1 structural protein Gag to the envelope protein (Env) is important for maximal virion infectivity. How the virus ensures the production of Gag and Env proteins in an appropriate ratio remains unknown. We report that HIV-1 exploits the host factor RuvB-like 2 (RVB2) to balance relative expression of Gag and Env for efficient production of infectious virions. RVB2 inhibits Gag expression by interacting with both the encoded Matrix (MA) domain of Gag protein and 5′ UTR of the translating mRNA and promoting mRNA degradation in a translation-dependent manner. This inhibitory activity of RVB2 is antagonized by Env through competitive interaction with MA, allowing Gag synthesis to proceed when Env levels are adequate for virion assembly. In HIV-1-positive patients, RVB2 levels positively correlate with viral loads and disease progression status. These findings reveal a mechanism by which HIV-1 regulates its protein expression.

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