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Journal of Virology, December 1998, p. 10029-10035, Vol. 72, No. 12
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Occult Systemic Infection and Persistent Simian Immunodeficiency Virus (SIV)-Specific CD4+-T-Cell Proliferative Responses in Rhesus Macaques That Were Transiently Viremic after Intravaginal Inoculation of SIV

Michael B. McChesney,1,2 Jennifer R. Collins,1 Ding Lu,1 Xusheng Lu,1 Judith Torten,1 Rhoda L. Ashley,3 Miles W. Cloyd,4 and Christopher J. Miller1,5,6,*

California Regional Primate Research Center,1 Department of Pathology, School of Medicine,2 Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine,5 and Center for Comparative Medicine,6 University of California---Davis, Davis, California 95616; Department of Laboratory Medicine, University of Washington, Seattle, Washington 981953; and Department of Microbiology, University of Texas Medical Branch at Galveston, Galveston, Texas 775554

Received 10 June 1998/Accepted 24 August 1998

The intact cervicovaginal mucosa is a relative barrier to the sexual transmission of human immunodeficiency virus type 1 (HIV-1). In the simian immunodeficiency virus (SIV) macaque model of HIV infection, seronegative transient viremia (STV; virus isolation positive followed by repeated negative cultures) occurs after intravaginal inoculation of a low dose of pathogenic SIVmac251 (C. J. Miller, M. Marthas, J. Torten, N. Alexander, J. Moore, G. Doncel, and A. Hendrickx, J. Virol. 68:6391-6400, 1994). Thirty-one adult female macaques that had been inoculated intravaginally with pathogenic SIVmac251 became transiently viremic. One monkey that had been culture negative for a year after SIV inoculation became persistently viremic and developed simian AIDS. No other STV monkey developed persistent viremia or disease. Results of very sensitive assays showed that 6 of 31 monkeys had weak SIV-specific antibody responses. SIV-specific antibodies were not detected in the cervicovaginal secretions of 10 STV monkeys examined. Twenty of 26 monkeys had lymphocyte proliferative responses to p55gag and/or gp130env antigens; 3 of 6 animals, including the monkey that became persistently viremic, had detectable cytotoxic T-lymphocyte (CTL) responses to SIV. At necropsy, lymphoid tissues and vaginal mucosa were virus culture negative, but in 10 of 10 animals, SIV provirus was detected by PCR using gag-specific primer pairs. Fifty percent of the PCR-positive tissue samples were also positive for SIV gag RNA by reverse transcriptase PCR. Thus, transient viremia following intravaginal inoculation of pathogenic SIV is associated with persistent, systemic infection, either latent or very low level productive. Atypical immune responses, characterized by lymphocyte proliferation and some CTL responses in the absence of conventionally detectable antibodies, develop in transiently viremic monkeys.

* Corresponding author. Mailing address: California Regional Primate Research Center, University of California---Davis, Davis, CA 95616-8542. Phone: (530) 752-0447. Fax: (530) 752-2880. E-mail: cjmiller{at}ucdavis.edu.

Journal of Virology, December 1998, p. 10029-10035, Vol. 72, No. 12
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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