Abstract
BackgroundHuman APOBEC3G (hA3G) has been identified as a cellular inhibitor of HIV-1 infectivity. Viral incorporation of hA3G is an essential step for its antiviral activity. Although the mechanism underlying hA3G virion encapsidation has been investigated extensively, the cellular source of viral hA3G remains unclear.ResultsPrevious studies have shown that hA3G forms low-molecular-mass (LMM) and high-molecular-mass (HMM) complexes. Our work herein provides evidence that the majority of newly-synthesized hA3G interacts with membrane lipid raft domains to form Lipid raft-associated hA3G (RA hA3G), which serve as the precursor of the mature HMM hA3G complex, while a minority of newly-synthesized hA3G remains in the cytoplasm as a soluble LMM form. The distribution of hA3G among the soluble LMM form, the RA LMM form and the mature forms of HMM is regulated by a mechanism involving the N-terminal part of the linker region and the C-terminus of hA3G. Mutagenesis studies reveal a direct correlation between the ability of hA3G to form the RA LMM complex and its viral incorporation.ConclusionsTogether these data suggest that the Lipid raft-associated LMM A3G complex functions as the cellular source of viral hA3G.
Highlights
IntroductionHuman APOBEC3G (hA3G) has been identified as a cellular inhibitor of HIV-1 infectivity
Human APOBEC3G has been identified as a cellular inhibitor of HIV-1 infectivity
Approximate 85% of total endogenous Human APOBEC3G (hA3G) in H9 cells presented in the P100, and a similar pattern was obtained from hA3G transiently expressing in 293T cells
Summary
Human APOBEC3G (hA3G) has been identified as a cellular inhibitor of HIV-1 infectivity. Viral incorporation of hA3G is an essential step for its antiviral activity. Human APOBEC3G (hA3G) has been identified as one of anti-HIV-1 host factors [1]. The virus counters hA3G’s anti-viral activity through the viral protein Vif (virion infectivity factor), which interacts with cytoplasmic hA3G as a part of Vif-Cul5-SCF complex, resulting in the ubiquitination and degradation of hA3G [3,4]. Viral encapsidation of hA3G is an essential step for its antiviral activity. If hA3G is encapsidated into the virions, can it exert its antiviral activity on the. The main cytoplasmic form of hA3G in H9 and 293T cells has been reported to be an enzymatically inactive, high-molecular-mass (HMM) ribonucleoprotein complex [13]. Biochemical studies have demonstrated the HMM hA3G complex associates with several cellular RNA binding proteins, as well as certain mRNAs and small non-coding RNAs [14,15,16]. hA3G has been shown to dynamically associate with various RNPs including ribosomes, miRNA-induced silencing complexes, RoRNPs, processing bodies, stress granules, and Staufen granules [14,16]
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