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

California Regional Primate Research Center, School of Medicine, University of California, Davis 95616, USA.
Journal of Virology (Impact Factor: 4.65). 08/2000; 74(13):6087-95. DOI: 10.1128/JVI.74.13.6087-6095.2000
Source: PubMed

ABSTRACT 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.

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Available from: Christopher James Miller, Aug 20, 2015
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    • "The laboratory-adapted env clones BaL and IIIB in pcDNA3.1 were described previously (Hu et al., 2000; Huang et al., 2012). MWS2 env was cloned from semen of a man who was known to have vaginal intercourse with a HIV-1 acutely infected woman (Hu et al., 2005), while CH811 env was cloned from a blood sample isolated from a Chinese patient as described previously (Hu et al., 2000). The T/F env clones were kindly provided by the Centre for HIV/AIDS Vaccine Immunology (CHAVI) (Hu et al., 2010; Keele et al., 2008). "
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    • "In non-human primate (NHP) studies, the infection of the genital epithelium pointed to DCs as first target cells for the virus (Hu et al, 2000; Spira et al, 1996). Infected DCs were detected in the pluristratified cervico-vaginal epithelium within 60 min from viral exposure, and thereafter accumulated within 2– 3 days beneath the epithelium (Hu et al, 2000; Spira et al, 1996). "
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    • "Studies have demonstrated that the primary infected cells present in the lamina propria of the cervicovaginal mucosa 48–72 hr after intravaginal exposure to SIV are T cells or submucosal DCs, but not epithelial LCs (Spira et al., 1996; Zhang et al., 1999). When vaginal tissue was examined within 1 hr following vaginal inoculation, however, up to Cell Host & Microbe 13, 77–86, January 16, 2013 ª2013 Elsevier Inc. 77 90% of SIV-infected cells were found to be LCs (Hu et al., 2000). Because only a single layer of columnar epithelium guards the endocervix and the transformation zone, the mucosal barrier can be easily breached by mechanisms such as the microtrauma associated with sexual intercourse, which provides immediate access to target cells, especially CD4 + T cells, in the submucosa (Haase, 2010). "
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