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Journal of Virology, July 2000, p. 6087-6095, Vol. 74, No. 13
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Simian Immunodeficiency Virus Rapidly Penetrates the Cervicovaginal Mucosa after Intravaginal Inoculation and Infects Intraepithelial Dendritic Cells

Jinjie Hu,1,dagger Murray B. Gardner,2,3 and Christopher J. Miller1,2,4,*

California Regional Primate Research Center,1 Center for Comparative Medicine,2 Department of Medical Pathology, School of Medicine,3 and Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine,4 University of California, Davis, California 95616

Received 1 February 2000/Accepted 31 March 2000

Despite recent insights into mucosal human immunodeficiency virus (HIV) transmission, the route used by primate lentiviruses to traverse the stratified squamous epithelium of mucosal surfaces remains undefined. To determine if dendritic cells (DC) are used by primate lentiviruses to traverse the epithelial barrier of the genital tract, rhesus macaques were intravaginally exposed to cell-free simian immunodeficiency virus SIVmac251. We examined formalin-fixed tissues and HLA-DR+-enriched cell suspensions to identify the cells containing SIV RNA in the genital tract and draining lymph nodes within the first 24 h of infection. Using SIV-specific fluorescent in situ hybridization combined with immunofluorescent antibody labeling of lineage-specific cell markers, numerous SIV RNA+ DC were documented in cell suspensions from the vaginal epithelium 18 h after vaginal inoculation. In addition, we determined the minimum time that the SIV inoculum must remain in contact with the genital mucosa for the virus to move from the vaginal lumen into the mucosa. We now show that SIV enters the vaginal mucosa within 60 min of intravaginal exposure, infecting primarily intraepithelial DC and that SIV-infected cells are located in draining lymph nodes within 18 h of intravaginal SIV exposure. The speed with which primate lentiviruses penetrate mucosal surfaces, infect DC, and disseminate to draining lymph nodes poses a serious challenge to HIV vaccine development.

* Corresponding author. Mailing address: Virology and Immunology Unit, California Regional Primate Research Center, University of California, Davis, CA 95616. Phone: (530) 752-8584. Fax: (530) 752-2880. E-mail: cjmiller{at}ucdavis.edu.

dagger Present address: Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Rockville, MD 20852.

Journal of Virology, July 2000, p. 6087-6095, Vol. 74, No. 13
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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