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J. Virol. doi:10.1128/JVI.01046-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Mode of Transmission Affects the Sensitivity of HIV-1 to Restriction by Rhesus TRIM5

Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA; Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Division of AIDS, Harvard Medical School, Boston, MA 02115, USA; VIRxSYS Corporation, Gaithersburg, Maryland 20877, USA; Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA

^* To whom correspondence should be addressed. Email: rileyj{at}mail.med.upenn.edu.

	Abstract

Rhesus (rh), but not human (hu), TRIM5 potently inhibits HIV infection and is thus a potentially valuable therapeutic tool. Primary human CD4 T cells engineered to express rhTRIM5 were highly resistant to cell-free HIV-1 infection. However, when co-cultured with unmodified T cells, rhTRIM5-expressing cells became highly permissive to HIV-1 infection. Physical separation of rhTRIM5-expressing cells and unmodified cells revealed that rhTRIM5 efficiently restricts cell-free but not cell-associated HIV transmission. Furthermore, we observed that HIV-infected human cells could infect rhesus CD4 T cells by cell-to-cell contact, but the infection was self-limiting. Subsequently, we noted that a spreading infection ensued when HIV-1-infected rhTRIM5-expressing human cells were cultured with huTRIM5- but not rhTRIM5-expressing cells. Our results suggest cell-associated HIV transmission in humans is blocked only when both donor and recipient cells express rhTRIM5. These studies further define the role of rhTRIM5 in cell-free and cell-associated HIV transmission and delineate the utility of rhTRIM5 in anti-HIV therapy.