Cul3-KLHL20 E3 ubiquitin ligase plays a key role in the arms race between HIV-1 Nef and host SERINC5 restriction

Abstract

SERINC5 is a host-restriction factor preventing HIV progeny entry, which is counteracted by interactions with HIV Nef. Here, Li et al. show that E3 ubiquitin ligase Cullin 3 polyubiquitinates SERINC5 at Lys 130 via K48- and K33-linked ubiquitin chains and provide evidence that this modification is not only required for its membrane localization and anti-viral activity but also relevant for Nef counteractive activity.