Setting the stage: host invasion by HIV

Abstract

For more than two decades, HIV has infected millions of people worldwide each year through mucosal transmission. Our knowledge of how HIV secures a foothold at both the molecular and cellular levels has expanded by recent investigations that have applied new technologies and used improved techniques to isolate ex vivo human tissue and generate in vitro cellular models, as well as more relevant in vivo animal challenge systems. Here, we review the current concepts of the immediate events that follow viral exposure at genital mucosal sites where most documented transmissions occur. Furthermore, we discuss the gaps in our knowledge that are relevant to future studies, which will shape strategies for effective HIV prevention.

Influence of Common Mucosal Co‐Factors on HIV Infection in the Female Genital Tract

“…It was first discovered as a disease that primarily affected men who have sex with men (MSM) and intravenous drug users but has evolved into an epidemic where currently approximately half of 34 million adults living with HIV globally are women. 1 Although vaginal intercourse carries a lower HIV transmission probability per exposure event than anal intercourse or parenteral inoculation, 2 the female genital tract (FGT) has been estimated to be the predominant site of HIV acquisition globally, with approximately 40% of all new infections originating at this mucosal site. 2,3 Thus, it has become increasingly clear that a better understanding of the microenvironment in the FGT is critical for developing strategies for the prevention of HIV transmission globally.…”

HIV-1 incorporation of host-cell–derived glycosphingolipid GM3 allows for capture by mature dendritic cells

“…Dendritic cells are postulated to be one of the first cells to contact virus, and are believed to play a central role in establishing infection and subsequent viral dissemination (2). The majority of HIV/dendritic cell (DC) interactions result in a virus that remains associated with DCs in an infectious state (3).…”

“…O f the estimated two and a half million new HIV infections that occur each year (1), approximately 85% are acquired at mucosal surfaces through sexual transmission (2). Dendritic cells are postulated to be one of the first cells to contact virus, and are believed to play a central role in establishing infection and subsequent viral dissemination (2).…”

Resistance to type 1 interferons is a major determinant of HIV-1 transmission fitness

“…In 2015, ∼2 million individuals were newly infected with HIV-1, the great majority of whom acquired the virus by sexual routes (1). Although a number of factors, such as high donor viral loads, genital inflammation, altered mucosal microbiota, and recipient gender, are known to increase the infection risk (2-4), virus transmission across intact mucosal surfaces is inherently inefficient, with only a small fraction (less than 1%) of unprotected sexual exposures leading to productive infection (5)(6)(7)(8). This inefficiency is exemplified by a stringent population bottleneck, in which only one or a limited number of variants from the diverse quasispecies of the transmitting donor establish the new infection (9).…”