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Science 30 April 1999:
Vol. 284. no. 5415, pp. 816 - 819
DOI: 10.1126/science.284.5415.816
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Reports

Distinct Pathogenic Sequela in Rhesus Macaques Infected with CCR5 or CXCR4 Utilizing SHIVs

Janet M. Harouse, 1 Agegnehu Gettie, 1 Rei Chin How Tan, 1 James Blanchard, 2 Cecilia Cheng-Mayer 1*

Infection of macaques with chimeric simian-human immunodeficiency virus (SHIV) provides an excellent in vivo model for examining the influence of envelope on HIV-1 pathogenesis. Infection with a pathogenic CCR5 (R5)-specific enveloped virus, SHIVSF162P, was compared with infection with the CXCR4 (X4)-specific SHIVSF33A.2. Despite comparable levels of viral replication, animals infected with the R5 and X4 SHIV had distinct pathogenic outcomes. SHIVSF162P caused a dramatic loss of CD4+ intestinal T cells followed by a gradual depletion in peripheral CD4+ T cells, whereas infection with SHIVSF33A.2 caused a profound loss in peripheral T cells that was not paralleled in the intestine. These results suggest a critical role of co-receptor utilization in viral pathogenesis and provide a reliable in vivo model for preclinical examination of HIV-1 vaccines and therapeutic agents in the context of the HIV-1 envelope protein.

1 Aaron Diamond AIDS Research Center, The Rockefeller University, 455 First Avenue, 7th Floor, New York, NY 10016, USA.
2 Tulane Regional Primate Research Center, Tulane University Medical Center, 18073 Three Rivers Road, Covington, LA 70433, USA.
*   To whom correspondence should be addressed. E-mail: cmayer{at}Adarc.org

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