Blocking HIV‐1 transmission in the female reproductive tract: from microbicide development to exploring local antiviral responses

Abstract

The majority of new HIV-1 infections are transmitted sexually by penetrating the mucosal barrier to infect target cells. The development of microbicides to restrain heterosexual HIV-1 transmission in the past two decades has proven to be a challenging endeavor. Therefore, better understanding of the tissue environment in the female reproductive tract may assist in the development of the next generation of microbicides to prevent HIV-1 transmission. In this review, we highlight the important factors involved in the heterosexual transmission of HIV-1, provide an update on microbicides' clinical trials, and discuss how different delivery platforms and local immunity may empower the development of next generation of microbicide to block HIV-1 transmission in the female reproductive tract.

Interferon epsilon promotes HIV restriction at multiple steps of viral replication

“…31 The development of a safe and effective HIV microbicide has met with significant challenges, with most microbicides causing damage to the vaginal mucosal surface, aiding the transmission of HIV across the mucosal barrier. 32 Currently, administration of pre-exposure prophylaxis (PrEP) anti-retroviral drugs is considered the most effective method for blocking transmission of HIV to uninfected individuals. 33 There are concerns, however, that PrEP could accelerate the transmission of drug-resistant HIV within particular regions where drugresistant HIV is already prevalent.…”

Dendritic Cells From the Cervical Mucosa Capture and Transfer HIV-1 via Siglec-1

“…As other sexually transmitted infections such as herpes virus or chlamydia infection trigger type I IFN responses in mucosal tissues via pDC recruitment and/or bacterial lipopolysaccharide exposure (55, 56), it would be important to explore the role of Siglec-1 in favoring HIV-1 acquisition, replication and dissemination in women with pre-existing sexually transmitted infections (2). Moreover, since inflammatory CD14 + CD11c + DCs are known to induce Th17 T-cell differentiation (57), and these are the preferential targets of viral infection in the cervix right after retroviral invasion (58), it would also be critical to evaluate the role of this Siglec-1 + DC subset on susceptibility to HIV-1 infection.…”

“…Women account for 51% of people living with HIV worldwide, and in 2017 this represented 18.8 million of females (1). Since HIV-1 infection is mostly acquired by sexual transmission (2), understanding the female genital tract immunobiology is imperative not only to halt novel infections, but also to design strategies that will limit HIV-1 spread within the mucosa and contain the virus during the early stages of infection. HIV-1 acquisition requires a series of orchestrated events that lead to systemic infection, beginning with viral entry through the genital epithelium and followed by the productive infection of distinct CD4 + target cells that reside within the mucosa.…”

HIV pre-exposure prophylaxis for women and infants prevents vaginal and oral HIV transmission in a preclinical model of HIV infection

“…a monolayer of columnar epithelial cells with tight junctions in the endocervix, endometrium and fallopian tubes (type I mucosa), and a multilayer of squamous epithelial cells in the vagina and ectocervix (type II mucosa). 40,41 HIV-susceptible cells have also been demonstrated in the oral cavity, which is protected by multiple layers of stratified epithelial cells. However, in comparison to adults, the oral mucosa of infants is incompletely stratified and contains lower levels of innate anti-HIV factors rendering it much more susceptible to HIV infection.…”