ARIH2 Is a Vif-Dependent Regulator of CUL5-Mediated APOBEC3G Degradation in HIV Infection.

ARIH2 Is a Vif-Dependent Regulator of CUL5-Mediated APOBEC3G Degradation in HIV Infection.
Cell Host Microbe. 2019 Jun 24;:
Authors: Hüttenhain R, Xu J, Burton LA, Gordon DE, Hultquist JF, Johnson JR, Satkamp L, Hiatt J, Rhee DY, Baek K, Crosby DC, Frankel AD, Marson A, Harper JW, Alpi AF, Schulman BA, Gross JD, Krogan NJ
Abstract
The Cullin-RING E3 ligase (CRL) family is commonly hijacked by pathogens to redirect the host ubiquitin proteasome machinery to specific targets. During HIV infection, CRL5 is hijacked by HIV Vif to target viral restriction factors of the APOBEC3 family for ubiquitination and degradation. Here, using a quantitative proteomics approach, we identify the E3 ligase ARIH2 as a regulator of CRL5-mediated APOBEC3 degradation. The CUL5Vif/CBFß complex recruits ARIH2 where it acts to transfer ubiquitin directly to the APOBEC3 targets. ARIH2 is essential for CRL5-dependent HIV infectivity in primary CD4+ T cells. Furthermore, we show that ARIH2 cooperates with CRL5 to prime other cellular substrates for polyubiquitination, suggesting this may represent a general mechanism beyond HIV infection and APOBEC3 degradation. Taken together, these data identify ARIH2 as a co-factor in the Vif-hijacked CRL5 complex that contributes to HIV infectivity and demonstrate the operation of the E1-E2-E3/E3-substrate ubiquitination mechanism in a viral infection context.
PMID: 31253590 [PubMed - as supplied by publisher]

Source: Cell Host and Microbe - June 23, 2019 Category: Microbiology Authors: Hüttenhain R, Xu J, Burton LA, Gordon DE, Hultquist JF, Johnson JR, Satkamp L, Hiatt J, Rhee DY, Baek K, Crosby DC, Frankel AD, Marson A, Harper JW, Alpi AF, Schulman BA, Gross JD, Krogan NJ Tags: Cell Host Microbe Source Type: research