Evolutionarily conserved requirement for core binding factor beta in the assembly of the human immunodeficiency virus/simian immunodeficiency virus Vif-cullin 5-RING E3 ubiquitin ligase.

ABSTRACT: The human immunodeficiency virus type 1 (HIV-1)-encoded virion infectivity factor (Vif) is required to inactivate the host restriction factor APOBEC3 by engaging Cullin 5 (Cul5)-RING ubiquitin ligase (CRL5). Core binding factor beta (CBF-?) is a novel regulator of Vif-CRL5 function; as yet, its mechanism of regulation remains unclear. In the present study, we demonstrate that CBF-? promotion of Vif-CRL5 assembly is independent of its influence on Vif stability and is also a conserved feature of primate lentiviral Vif proteins. Furthermore, CBF-? is critical for the formation of the Vif-ElonginB/ElonginC-Cul5 core E3 ubiquitin ligase complex in vitro. CBF-? from diverse vertebrate species supported HIV-1 Vif function, indicating the conserved nature of Vif-CBF-? interfaces. Considering the importance of the interaction between Vif and CBF-? in viral CRL5 function, disrupting this interaction represents an attractive pharmacological intervention against HIV-1.HIV-1 encodes virion infectivity factor (Vif) to inactivate its host's antiviral APOBEC3 proteins. Vif triggers APOBEC3 degradation by forming Vif-Cullin 5 (Cul5)-RING ubiquitin ligase (CRL5). Core binding factor beta (CBF-?) is a novel regulator of Vif-CRL5 function whose mechanism of regulation remains poorly defined. In the present study, we demonstrate that the promotion of Vif-CRL5 assembly by CBF-? can be separated from its influence on Vif stability. The promotion of Vif-CRL5 assembly, but not the influence on Vif stability, is conserved among primate lentiviral Vif proteins: we found that CBF-? from diverse vertebrate species supported HIV-1 Vif function. Considering the importance of the interaction between Vif and CBF-? in viral CRL5 function and HIV-1 replication, disrupting this interaction is an attractive strategy against HIV-1.

SUBMITTER: Han X 

PROVIDER: S-EPMC3957933 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature