Cellular proteins called "restriction factors" can serve as powerful blockades to HIV replication, but the virus possesses elaborate strategies to circumvent these barriers. First, we discuss general hallmarks of a restriction factor. Second, we review how the viral Vif protein protects the viral genome from lethal levels of cDNA deamination by promoting APOBEC3 protein degradation; how the viral Vpu, Env, and Nef proteins facilitate internalization and degradation of the virus-tethering protein BST-2/tetherin; and how the viral Vpx protein prevents the premature termination of reverse transcription by degrading the dNTPase SAMHD1. These HIV restriction and counter-restriction mechanisms suggest strategies for new therapeutic interventions.
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