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CD4+ Lymphocytopenia in Acute Infection of Asian Macaques by a Vaginally Transmissible Subtype-C, CCR5-Tropic Simian/Human Immunodeficiency Virus (SHIV)

Chen Zhiwei; Zhao, Xiuqing; Huang, Yaoxing; Gettie, Agegnehu; Ba, Lei; Blanchard, James; Ho, David D.
JAIDS Journal of Acquired Immune Deficiency Syndromes: June 1st, 2002
doi: 10.1097/01.QAL0000017963.22053.47
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An R5-tropic SHIVCHN19P4 was previously generated using a primary HIV-1 subtype-C envelope. We have further characterized this SHIV in two species of macaques. To determine whether this isolate is transmissible vaginally, female pigtailed macaques were inoculated with 2x103 TCID50 of SHIVCHN19P4 by the vaginal route. Animals became infected with a high peak plasma viremia (>107 viral copies/mL) and rapid seroconversion. The viremia was accompanied by CD4+ lymphocytopenia in the gut lamina propria lymphocyte (LPL) population. Comparable CD4+ T-cell loss was not seen in peripheral blood and colonic lymph nodes. These findings demonstrate a unique R5-tropic SHIV that can be used to study enveloperelated issues in vaginal transmission of the most prevalent subtype of HIV-1. We also found that rhesus macaques intravenously inoculated with 1 × 103 TCID50 of SHIVCHN19P4 became infected and showed CD4+ lymphocytopenia in the gut LPL population. Despite inactivation of the vpu gene in SHIVCHN19P4, the virus appears to target mainly gut-associated lymphoid tissues during the initial stage of infection as has been described for SHIVSF162P, another R5-tropic (subtype B) recombinant virus. Our data indicate that the R5-mediated CD4+ lymphocytopenia in the gut is likely independent of HIV-1 genotypes and of the function of vpu at the acute phase of viral infection.

Address correspondence and reprint requests to David D. Ho. The Aaron Diamond AIDS Research Center, 455 First Avenue, 7th Floor, New York, NY 10016 U.S.A.; e-mail: dho@adarc.org

Equal contributions to this article were made by first two authors.

This study was supported by an AmFAR grant 02663-27-RGM to Z. Chen and a gift from Donald Pels. Additional funds were provided by the National Institutes of Health grants (1F32AI10256. AI 35168, RR00164), by the Population Council Fund, and by the Irene Diamond Fund.

Manuscript received February 1, 2002: accepted March 25, 2002.

© 2002 Lippincott Williams & Wilkins, Inc.