apobec3g inhibits elongation of hiv-1 reverse transcriptsapobec3g抑制hiv - 1逆转成绩单的伸长.pdf

APOBEC3G Inhibits Elongation of HIV-1 Reverse Transcripts 1¤ 1 2 2 1 Kate N. Bishop , Mohit Verma , Eun-Young Kim , Steven M. Wolinsky , Michael H. Malim * 1 Department of Infectious Diseases, King’s College London School of Medicine, Guy’s Hospital, London, United Kingdom, 2 Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America Abstract APOBEC3G (A3G) is a host cytidine deaminase that, in the absence of Vif, restricts HIV-1 replication and reduces the amount of viral DNA that accumulates in cells. Initial studies determined that A3G induces extensive mutation of nascent HIV-1 cDNA during reverse transcription. It has been proposed that this triggers the degradation of the viral DNA, but there is now mounting evidence that this mechanism may not be correct. Here, we use a natural endogenous reverse transcriptase assay to show that, in cell-free virus particles, A3G is able to inhibit HIV-1 cDNA accumulation not only in the absence of hypermutation but also without the apparent need for any target cell factors. We find that although reverse transcription initiates in the presence of A3G, elongation of the cDNA product is impeded. These data support the model that A3G reduces HIV-1 cDNA levels by inhibiting synthesis rather than by inducing degradation. Citation: Bishop KN, Verma M, Kim E-Y, Wolinsky SM, Malim MH (2008) APOBEC3G Inhibits Elongation of HIV-1 Reverse Transcripts. PLoS Pathog 4(12): e1000231. doi:10.1371/journal.ppat.1000231 Editor: Thomas J. Hope, Northwestern University, United States of America Received September 15, 2008; Accepted November 5, 2008; Published December 5, 2008 Copyright: 2008