HIV infection of the genital mucosa in women

Abstract

The vast majority of new HIV infections are acquired via the genital and rectal mucosa. Here, we provide an overview of our current knowledge of how HIV establishes local infection, with an emphasis on viral invasion through the female genital tract. Studies using human explant tissues and in vivo animal studies have improved our understanding of the cellular and molecular pathways of infection; this information could be harnessed to design effective HIV vaccines and microbicides.

The integrin α 4 β 7 forms a complex with cell-surface CD4 and defines a T-cell subset that is highly susceptible to infection by HIV-1

“…It encounters multiple barriers to successful transmission (15) as it migrates through highly compartmentalized mucosal tissues. Moreover, it has been suggested that dendritic cells facilitate this migration (15).…”

“…It encounters multiple barriers to successful transmission (15) as it migrates through highly compartmentalized mucosal tissues. Moreover, it has been suggested that dendritic cells facilitate this migration (15). Neither the biopsies that we analyzed nor our culture systems reflect this complexity; however, the capacity of ␣ 4 ␤ 7 to capture HIV-1 virions (9) suggests that it can facilitate infection of activated cells in vitro.…”

“…Thus, we cannot exclude the possibility that the initial and most relevant interaction between HIV-1 and ␣ 4 ␤ 7 occurs in the genital mucosa in the earliest days following exposure. Whether this interaction involves free virions, infected cells, or virions sequestered by dendritic cells (15,30) remains to be determined.…”

Role of Semen in Modulating the Female Genital Tract Microenvironment – Implications for HIV Transmission

“…The intra-epithelial processes of the LCs help convey HIV to the submucosal lymphocytes, and following productive infection of these CD4 + T cell populations; the virus is able to propagate and disseminate via lymphatic mechanisms. 31,32 Studies from non-human primates suggest that SIV penetrates the cervicovaginal epithelium and is able to infect a small population of cells within an hour. 30,33 Recently, human cervical explant and in vivo macaque exposure studies using photoactivatable-labeled virions have shown that HIV-1 can readily penetrate both intact columnar and squamous epithelium; however, the cervicovaginal epithelium is highly susceptible to viral infiltration via 'diffusive percolation' through interstitial spaces, while HIV-1 entry is impeded at the endocervical epithelium by mucus production.…”

“…74,86,87 LCs, present in cervicovaginal mucosa, are among the primary targets of HIV-1/SIV. 30,31,88,89 LCs are able to capture HIV-1 virions and transport them to the draining lymph nodes where the virions can be transmitted to T cells for productive infection, 27,[88][89][90] although there is some evidence to suggest viral particles captured by LCs are internalized and rendered incapable of infection. 90 In women, semen-enhanced infiltration of LCs into the genital epithelium has been demonstrated.…”