ARIH2 is a novel Vif-dependent regulator of CUL5-mediated APOBEC3G degradation in HIV infection

ABSTRACT: Discovery of novel host-virus interactions leads to a better understanding of mechanisms underlying infection and points to potential therapeutic targets at the interface between virus and host proteins. Recently, global, virus-host interaction networks have been mapped using affinity purification-mass spectrometry (AP-MS) approaches, but these studies do not provide information about dynamic remodeling of host complexes during infection. Here, we describe a novel quantitative proteomics approach in the context of HIV infection to unravel dynamics of the Cullin RING E3 ligase 5 (CRL5) complex, which is hijacked by HIV Vif to degrade the viral restriction factor of the APOBEC3 family. Generating a dynamic and quantitative interaction network of CRL5 under various infection conditions, we identify the E3 ligase ARIH2 as novel regulator of APOBEC3G degradation, which is essential for HIV infectivity in primary CD4+ T-cells. ARIH2 acts in a “tag-team” mechanism that accelerates ubiquitin chain formation on APOBEC3G through CUL5Vif/CBFß by priming the substrate with mono-ubiquitination. Finally, our data suggest a general role for ARIH2 in CRL5 substrate ubiquitination in host cells.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): T Cell

DISEASE(S): Human Immunodeficiency Virus Infectious Disease

SUBMITTER: Ruth Huttenhain  

LAB HEAD: Nevan J. Krogan

PROVIDER: PXD009012 | Pride | 2019-04-11

REPOSITORIES: Pride