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J Virol, August 1998, p. 6858-6866, Vol. 72, No. 8
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

CXCR4 Is Required by a Nonprimate Lentivirus: Heterologous Expression of Feline Immunodeficiency Virus in Human, Rodent, and Feline Cells

Eric M. Poeschla1,* and David J. Looney1,2,*

Department of Medicine, University of California, San Diego,1 and Infectious Diseases Division, Veterans Administration Medical Center,2 La Jolla, California

Received 30 September 1997/Accepted 12 May 1998

A heterologous feline immunodeficiency virus (FIV) expression system permitted high-level expression of FIV proteins and efficient production of infectious FIV in human cells. These results identify the FIV U3 element as the sole restriction to the productive phase of replication in nonfeline cells. Heterologous FIV expression in a variety of human cell lines resulted in profuse syncytial lysis that was FIV env specific, CD4 independent, and restricted to cells that express CXCR4, the coreceptor for T-cell-line-adapted strains of human immunodeficiency virus. Stable expression of human CXCR4 in CXCR4-negative human and rodent cell lines resulted in extensive FIV Env-mediated, CXCR4-dependent cell fusion and infection. In feline cells, stable overexpression of human CXCR4 resulted in increased FIV infectivity and marked syncytium formation during FIV replication or after infection with FIV Env-expressing vectors. The use of CXCR4 is a fundamental feature of lentivirus biology independent of CD4 and a shared cellular link to infection and cytopathicity for distantly related lentiviruses that cause AIDS. Their conserved use implicates chemokine receptors as primordial lentivirus receptors.

* Corresponding author. Mailing address for E. M. Poeschla: Department of Medicine 0665, University of California, San Diego, La Jolla, CA 92093-0665. Phone: (619) 534-4304. Fax: (619) 552-7416. E-mail: epoeschla{at}ucsd.edu. Mailing address for D. J. Looney: Department of Medicine 0678, University of California, San Diego, La Jolla, CA 92093-0678. Phone: (619) 552-8585, ext. 2626. Fax: (619) 552-7416. E-mail: dlooney{at}ucsd.edu.

J Virol, August 1998, p. 6858-6866, Vol. 72, No. 8
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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