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Journal of Virology, September 2009, p. 8646-8654, Vol. 83, No. 17
0022-538X/09/$08.00+0     doi:10.1128/JVI.00020-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Cytoplasmic APOBEC3G Restricts Incoming Vif-Positive Human Immunodeficiency Virus Type 1 and Increases Two-Long Terminal Repeat Circle Formation in Activated T-Helper-Subtype Cells{triangledown}

Michael L. Vetter1 and Richard T. D'Aquila1,2*

Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee,1 Department of Medicine, Division of Infectious Diseases, Vanderbilt University School of Medicine, Nashville, Tennessee2

Received 5 January 2009/ Accepted 11 June 2009

Cytoplasmic APOBEC3G has been reported to block wild-type human immunodeficiency virus type 1 (HIV-1) infection in some primary cells. It is not known whether cytoplasmic APOBEC3G has residual activity in activated T cells, even though virion-packaged APOBEC3G does restrict HIV-1 in activated T cells. Because we found that APOBEC3G expression is greater in activated CD4+ T-helper type 1 (Th1) lymphocytes than in T-helper type 2 (Th2) lymphocytes, we hypothesized that residual target cell restriction of incoming Vif-positive virions that lack APOBEC3G, if present, would be greater in Th1 than Th2 lymphocytes. Infection of activated Th1 cells with APOBEC3-negative virions did result in decreased amounts of early and late reverse transcription products and integrated virus relative to infection of activated Th2 cells. Two-long terminal repeat (2-LTR) circles, which are formed in the nucleus when reverse transcripts do not integrate, were increased after APOBEC3-negative virus infection of activated Th1 cells relative to infection of activated Th2 cells. In contrast, 2-LTR circle forms were decreased after infection of APOBEC3G-negative cells with APOBEC3G-containing virions relative to APOBEC3G-negative virions and with Th1 cell-produced virions relative to Th2 cell-produced virions. Increasing APOBEC3G in Th2 cells and decreasing APOBEC3G in Th1 cells modulated the target cell phenotypes, indicating causation by APOBEC3G. The comparison between activated Th1 and Th2 cells indicates that cytoplasmic APOBEC3G in activated Th1 cells partially restricts reverse transcription and integration of incoming Vif-positive, APOBEC3G-negative HIV-1. The differing effects of cytoplasmic and virion-packaged APOBEC3G on 2-LTR circle formation indicate a difference in their antiviral mechanisms.

* Corresponding author. Mailing address: Vanderbilt University School of Medicine, 1161 21st Avenue South, AA2205E Medical Center North, Nashville, TN 37232-2358. Phone: (615) 322-8972. Fax: (615) 322-3171. E-mail: richard.daquila{at}vanderbilt.edu

{triangledown} Published ahead of print on 17 June 2009.

Journal of Virology, September 2009, p. 8646-8654, Vol. 83, No. 17
0022-538X/09/$08.00+0     doi:10.1128/JVI.00020-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Moreno-Fernandez, M. E., Zapata, W., Blackard, J. T., Franchini, G., Chougnet, C. A. (2009). Human Regulatory T Cells Are Targets for Human Immunodeficiency Virus (HIV) Infection, and Their Susceptibility Differs Depending on the HIV Type 1 Strain. J. Virol. 83: 12925-12933 [Abstract] [Full Text]  


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