APOBEC3 proteins are a family of cytidine deaminases that exhibit broad antiretroviral activity. Among APOBEC3 proteins, APOBEC3G (hA3G) and APOBEC3F (hA3F) exhibit the most potent anti-HIV-1 activities. Although the incorporation of hA3F into virions is a prerequisite for exerting its antiviral function, the detail mechanism underlying remains incompletely understood. In this work, we present data showing that the nucleocapsid (NC) domain of HIV-1 Gag and a linker sequence between the two cytidine deaminase domains within hA3F, i.e., 104-156 amino acids, are required for viral packaging of hA3F. A detailed mapping study reveals that the cluster of basic residues surrounding the N-terminal zinc finger (ZF) and the linker region between the ZFs of HIV-1 NC play an important role in A3F incorporation, in addition, at least one of two ZFs is required. A hA3F fragment is able to compete with both hA3G and hA3F for viral incorporation, suggesting a common mechanism underlying virion encapsidation of hA3G and hA3F. Taken together, these results shed a light on the detail mechanism underlying viral incorporation of hA3F.
Keywords: APOBEC3F; APOBEC3G; HIV-1; Incorporation; NC.
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