Transmission of HIV‐1 by Primary Human Uterine Epithelial Cells and Stromal Fibroblasts

Abstract

Women can become infected with human immunodeficiency virus type 1 (HIV-1) after the heterosexual transmission of virus from an infected male partner. To understand the events that result in transmission of HIV-1 across the female reproductive tract, we characterized the life-cycle events of HIV-1 in primary cultures of human uterine epithelial cells and stromal fibroblasts. Epithelial cells and stromal fibroblasts released virus particles after exposure to either X4-or R5-tropic strains of HIV-1. Virus released by these cells was able to infect CD4 + T cells. When exposed to an X4-tropic strain of HIV-1, these cells supported HIV-1 reverse transcription, integration, and viral DNA transcription. When exposed to an R5-tropic strain, however, these cells released unmodified virus. These data suggest that uterine cells are targets for productive infection with X4-tropic strains and release unmodified R5-tropic viruses that would then be able to infect submucosal target cells, including T cells and macrophages.Although heterosexual transmission is the predominant mechanism by which women acquire HIV-1 infection [1][2][3][4], our knowledge about the viral and host factors that lead to infection is limited. Identifying the cell population initially infected within the female reproductive tract (FRT) and the putative mechanisms by which HIV-1 is disseminated to distal sites is important to our understanding of the pathogenesis of HIV-1. Moreover, defining the mechanisms and conditions that either promote or inhibit HIV-1 infection within the FRT is necessary for the design and development of preventative measures.Studies to identify cell populations within the FRT that become infected have focused on cell lines or primary cells and tissues from the lower FRT [5,6].

Selective sequestration of X4 isolates by human genital epithelial cells: Implication for virus tropism selection process during sexual transmission of HIV

“…6). In contradiction with our data, Asin et al [2004] showed that uterine epithelial cells, infected by an X4 strain of HIV, were able to produce infectious particles and to transmit the infection to PBMCs. However, the level of HIV production reported in the latter study was relatively low and highly variable from one cell line to another, questioning the relevance of this observation with regards to a significant participation of these cells in the initial spread of X4 strains.…”

“…This finding was not linked to exogenous genomic viral material since no proviral DNA was found in cells treated with AZT or rhSDF-1 and incubated with LAI. Accordingly, using primary human uterine cells, Asin et al [2004] demonstrated the specific integration of an X4 (and not R5) HIV isolate. Although our results evidenced a more efficient integration of HIV DNA inside HEC1A compared to CaSki, SiHa or normal human vaginal cells, the use of a sensitive alu-gag PCR technique allowed us to demonstrate a weak but significant X4 HIV integration inside the latter.…”

“…3), and that was used previously as a model for the study of HIV/genital epithelial cell interactions [Hocini et al, 2001;Asin et al, 2004]. Of interest, despite the integration of HIV proviral DNA by these cells, no HIV particles were found in the cell supernatants.…”

Primary Human Mammary Epithelial Cells Endocytose HIV-1 and Facilitate Viral Infection of CD4 + T Lymphocytes

“…The first round of the HIV-1 integration PCR was performed by using the Alu sense primer (5Ј-GCCTCCCAAAGTGC TGGGATTA-3Ј) (IDT), which binds to short DNA sequences occurring in multiple locations throughout the human genome, and the HIV-1 Gag antisense primer (5Ј-CCTGCGTCGAGAGAGCTCCTCTGG-3Ј) (IDT) (3). Five microliters of first-round product was then used in nested PCR, with the LTR sense primer M667 (IDT) and the antisense primer AA55 (IDT) (3). Products from the second-round PCR were run on 1% agarose gels with ethidium bromide to detect an expected 140-bp fragment.…”

Current concepts of HIV transmission

“…There are conflicting reports regarding the ability of ECs to be infected by HIV, but some studies have shown that ECs could be targets for productive infection [14,15]. Studies using primary ECs suggest that ECs are permissive to X4 HIV isolates but not R5 HIV and that captured R5 viruses are readily released [14].…”