HIV-1 and SUMOylation

Abstract

Background The HIV virus hijacks cellular machineries to replicate. Post-translational modifications, like acetylation, phosphorylation or ubiquitination, are no exception. We are interested in studying the interplay between HIV and the SUMOylation pathway. SUMOylation occurs via an enzymatic cascade requiring an E1 activating enzyme (SAE1/SAE2 heterodimer) and an E2 conjugating enzyme (Ubc9). This modification is reversible thanks to SUMO isopeptidases (SENPs). Despite Ubc9 alone being sufficient to transfer SUMO moieties to acceptor lysine residues in vitro, E3 SUMO ligases promote specificity and/or efficiency of SUMOylation in vivo. So far, several E3 SUMO ligases have been characterized, such as nuclear pore complex component Ran-binding protein 2 (RanBP2) and protein-inhibitor of activated STAT (PIAS) family proteins. We have recently shown that HIV integrase, the viral enzyme that is responsible for viral genome integration into host cellular chromosome, is SUMOylated, and that virions harboring a SUMOylation-defective integrase are less infectious than WT viruses. Our data suggest that this modification is important for efficient viral replication.