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- Title
Cellular APOBEC3G restricts HIV-1 infection in resting CD4<sup>+</sup> T cells.
- Authors
Chiu, Ya-Lin; Soros, Vanessa B.; Kreisberg, Jason F.; Stopak, Kim; Yonemoto, Wes; Greene, Warner C.
- Abstract
In contrast to activated CD4+ T cells, resting human CD4+ T cells circulating in blood are highly resistant to infection with human immunodeficiency virus (HIV). Whether the inability of HIV to infect these resting CD4+ T cells is due to the lack of a key factor, or alternatively reflects the presence of an efficient mechanism for defence against HIV, is not clear. Here we show that the anti-retroviral deoxycytidine deaminase APOBEC3G strongly protects unstimulated peripheral blood CD4+ T cells against HIV-1 infection. In activated CD4+ T cells, cytoplasmic APOBEC3G resides in an enzymatically inactive, high-molecular-mass (HMM) ribonucleoprotein complex that converts to an enzymatically active low-molecular-mass (LMM) form after treatment with RNase. In contrast, LMM APOBEC3G predominates in unstimulated CD4+ T cells, where HIV-1 replication is blocked and reverse transcription is impaired. Mitogen activation induces the recruitment of LMM APOBEC3G into the HMM complex, and this correlates with a sharp increase in permissivity for HIV infection in these stimulated cells. Notably, when APOBEC3G-specific small interfering RNAs are introduced into unstimulated CD4+ T cells, the early replication block encountered by HIV-1 is greatly relieved. Thus, LMM APOBEC3G functions as a potent post-entry restriction factor for HIV-1 in unstimulated CD4+ T cells. Surprisingly, sequencing of the reverse transcripts slowly formed in unstimulated CD4+ T cells reveals only low levels of dG?dA hypermutation, raising the possibility that the APOBEC3G-restricting activity may not be strictly dependent on deoxycytidine deamination.
- Publication
Nature, 2005, Vol 435, Issue 7038, p108
- ISSN
0028-0836
- Publication type
Academic Journal
- DOI
10.1038/nature03493