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Journal of Virology, November 2008, p. 11117-11128, Vol. 82, No. 22
0022-538X/08/$08.00+0     doi:10.1128/JVI.01046-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Mode of Transmission Affects the Sensitivity of Human Immunodeficiency Virus Type 1 to Restriction by Rhesus TRIM5{alpha} {triangledown}

Max W. Richardson,1,2 Richard G. Carroll,1 Matthew Stremlau,3 Nikolay Korokhov,4 Laurent M. Humeau,4 Guido Silvestri,2 Joseph Sodroski,3,5 and James L. Riley1,2*

Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104,1 Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104,2 Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Division of AIDS, Harvard Medical School, Boston, Massachusetts 02115,3 VIRxSYS Corporation, Gaithersburg, Maryland 20877,4 Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 021155

Received 19 May 2008/ Accepted 28 August 2008

Rhesus TRIM5{alpha} (rhTRIM5{alpha}), but not human TRIM5{alpha} (huTRIM5{alpha}), potently inhibits human immunodeficiency virus (HIV) infection and is thus a potentially valuable therapeutic tool. Primary human CD4 T cells engineered to express rhTRIM5{alpha} were highly resistant to cell-free HIV type 1 (HIV-1) infection. However, when cocultured with unmodified T cells, rhTRIM5{alpha}-expressing cells became highly permissive to HIV-1 infection. Physical separation of rhTRIM5{alpha}-expressing cells and unmodified cells revealed that rhTRIM5{alpha} 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{alpha}-expressing human cells were cultured with huTRIM5{alpha}- but not rhTRIM5{alpha}-expressing cells. Our results suggest that cell-associated HIV transmission in humans is blocked only when both donor and recipient cells express rhTRIM5{alpha}. These studies further define the role of rhTRIM5{alpha} in cell-free and cell-associated HIV transmission and delineate the utility of rhTRIM5{alpha} in anti-HIV therapy.

* Corresponding author. Mailing address: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104. Phone: (215) 573-6792. Fax: (215) 573-8590. E-mail: rileyj{at}mail.med.upenn.edu

{triangledown} Published ahead of print on 3 September 2008.

Journal of Virology, November 2008, p. 11117-11128, Vol. 82, No. 22
0022-538X/08/$08.00+0     doi:10.1128/JVI.01046-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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