RETRACTED: Cellular APOBEC3G restricts HIV-1 infection in resting CD4+ T cells (Retracted Article. See vol 466, pg 276, 2010)

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)(1-4). 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(5) 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(1-3). 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.