In order to achieve a persistent infection, viruses must overcome the host immune system. Host restriction factors dominantly block virus transmission, but are subject to down regulation by viral accessory proteins. HIV encodes several accessory factors that overcome different cellular restriction factors. For example, the HIV-1 protein Vif down regulates the human APOBEC3 family of restriction factors by targeting them for proteolysis by the ubiquitin-proteasome pathway. Recently, this function was shown to require the transcription cofactor CBFβ, which acts as a template to assist in Vif folding and allow for assembly of an APOBEC3-targeting E3 ligase complex. In uninfected cells, CBFβ is an essential binding partner of RUNX transcription factors. By binding CBFβ, Vif has also been shown to perturb transcription of genes regulated by the RUNX proteins, including restrictive APOBEC3 family members. Here we review how the link between CBFβ and Vif supports transcriptional and post-transcriptional repression of innate immunity. The ability of a single viral protein to coopt multiple host pathways is an economical strategy for a pathogen with limited protein coding capacity to achieve a productive infection.
Keywords: APOBEC3; HIV; Innate immunity; RUNX; Restriction factors; Transcription; Vif.