Abstract
In the context of HIV sexual transmission at the genital mucosa, initial interactions between the virus and the mucosal immunity determine the outcome of the exposure. Hence, these interactions have been deeply explored in attempts to undercover potential targets for developing preventative strategies. The knowledge gained has led to propose a hypothetical model for mucosal HIV transmission. Subsequent research studies on this topic further revealed new mechanisms and identified new host-HIV interactions. This review aims at integrating these findings to inform better and update the current model of HIV transmission. At the earliest stage of virus exposure, the epithelial integrity and the presence of antiviral factors are critical in preventing viral entry to the submucosa. However, the virus has been shown to enter to the submucosa in the presence of physical abrasion or via epithelial transmigration using paracellular passage or transcytosis mechanisms. The efficiency of these processes is greater with cell-associated viral inoculums and can be influenced by the presence of viral and immune factors, and by the structure of the exposed epithelium. Once the virus reaches the submucosa, dendritic cells and fibroblasts, as recently described, have been shown in vitro of being capable of facilitating the transfer of viral particles to susceptible cells, leading to viral dissemination, most likely in a trans-infection manner. The presence of activated CD4+ T cells in submucosa increases the probability of infection, where the predominant microbiota could be implicated through the modulation of an inflammatory microenvironment. Other factors such as genital fluids and hormones could also play an essential role in HIV transmission. Here, we review the most recent evidence described for mucosal HIV-transmission contributing with the understanding of this phenomenon.
Highlights
HIV infection remains one of the most critical health problems worldwide, with close to 37 million people infected in 2017 [1]
The virus can pass across the mucosal epithelium by two mechanisms: (i) paracellular passage and (ii) transcytosis; it is proposed that the choice of one or the other may rely on the type and the intrinsic characteristic of the epithelium [3]
Viral particles bind to the epithelial cell surface molecules like heparan sulfate proteoglycans (HSPGs) or Galcer to be transported into the intracellular compartment [52, 71, 81, 82]
Summary
HIV infection remains one of the most critical health problems worldwide, with close to 37 million people infected in 2017 [1]. Some of the well described mechanisms include: (i) the lack of expression of the viral co-receptor CCR5 [18]; (ii) increased production of the chemokines MIP-1α/β, RANTES or SDF-1 [19]; (iii) apoptosis of target cells [20]; (iv) high expression of anti-HIV factors like SLPI, Defensins, Cathelicidin, TRIM5α, APOBEC-3G, SAMHD-1, Serpina, and Elafin [21, 22]; (v) reduced IRF-1 expression [23, 24]; (vi) increased activity of natural killer (NK) [25, 26], and dendritic cells (DC) [27]; (vii) the presence of neutralizing IgA antibodies [26, 28]; and (viii) an effective and polyfunctional response of HIV-1-specific CD4+ and CD8+ T cells [29, 30] Most of these resistance mechanisms have been observed at the mucosa of HESNs, highlighting the importance of the initial interactions between the virus and the mucosal immune system in predicting the eradication or establishment, and dissemination of the infection. This review has grouped these new findings with the previously defined model, providing a holistic model of HIV transmission at genital mucosa
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
