Inhibition of \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{tRNA}_{3}^{\mathrm{Lys}}\) \end{document}-Primed Reverse Transcription by Human APOBEC3G during Human Immunodeficiency Virus Type 1 Replication

• DOI: 10.1128/jvi.01038-06
• Publication Date: 2006-11-13T19:03:38Z
• Authors: Fei Guo; Shan Cen; Meijuan Niu; Jenan Saadatmand; Lawrence Kleiman
• Keywords: 0303 health sciences; Gene Products, vif; APOBEC-3G Deaminase; Nucleoside Deaminases; Reverse Transcription; Virus Replication; Cell Line; 3. Good health; Repressor Proteins; 03 medical and health sciences; Gene Expression Regulation; Cytidine Deaminase; HIV-1; vif Gene Products, Human Immunodeficiency Virus; Humans

ABSTRACT

Cells are categorized as being permissive or nonpermissive according to their ability to produce infectious human immunodeficiency virus type 1 (HIV-1) lacking the viral protein Vif. Nonpermissive cells express the human cytidine deaminase APOBEC3G (hA3G), and Vif has been shown to bind to APOBEC3G and facilitate its degradation. Vif-negative HIV-1 virions produced in nonpermissive cells incorporate hA3G and have a severely reduced ability to produce viral DNA in newly infected cells. While it has been proposed that the reduction in DNA production is due to hA3G-facilitated deamination of cytidine, followed by DNA degradation, we provide evidence here that a decrease in the synthesis of the DNA by reverse transcriptase may account for a significant part of this reduction. During the infection of cells with Vif-negative HIV-1 produced from 293T cells transiently expressing hA3G, much of the inhibition of early (≥50% reduction) and late (≥95% reduction) viral DNA production, and of viral infectivity (≥95% reduction), can occur independently of DNA deamination. The inhibition of the production of early minus-sense strong stop DNA is also correlated with a similar inability of tRNA 3 Lys to prime reverse transcription. A similar reduction in tRNA 3 Lys priming and viral infectivity is also seen in the naturally nonpermissive cell H9, albeit at significantly lower levels of hA3G expression.