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The roles of APOBEC3G complexes in the incorporation of APOBEC3G into HIV-1.
来源: 时间:2014-07-08 浏览次数:3800
The roles of APOBEC3Gcomplexes in the incorporation of APOBEC3G into HIV-1.
  • Institute of Medicinal Biotechnology, Chinese Academy of Medical Science, Beijing, China ; Lady Davis Institute for Medical Research and McGill AIDS Centre, Jewish General Hospital, Montreal, Quebec, Canada ; Microbiology & Immunology, McGill University, Montreal, Quebec, Canada.
Abstract
BACKGROUND:
The incorporation of human APOBEC3G (hA3G) into HIV is required for exerting its antiviral activity, therefore the mechanism underlying hA3G virion encapsidation has been investigated extensively. hA3G was shown to form low-molecular-mass (LMM) and high-molecular-mass (HMM) complexes. The function of different forms of hA3G in its viral incorporation remains unclear.
METHODOLOGY/PRINCIPAL FINDINGS:
In this study, we investigated the subcellular distribution and lipid raft association of hA3G using subcellular fractionation, membrane floatation assay and pulse-chase radiolabeling experiments respectively, and studied the correlation between the ability of hA3G to form the different complex and its viral incorporation. 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 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.
CONCLUSIONS/SIGNIFICANCE:
Together these data suggest that the Lipid raft-associated LMM A3G complex functions as the cellular source of viral hA3G.