How do viral and host factors modulate the sexual transmission of HIV? Can transmission be blocked?

Kalpana Gupta, Per Johan Klasse, Kalpana Gupta, Per Johan Klasse

Abstract

A better understanding of sexual transmission, say the authors, will enable more rational design of vaccines and microbicides and potential combinations of the two.

Conflict of interest statement

Competing interests: The authors declare that no competing interests exist.

Figures

Figure 1. Early Events during Sexual Transmission…
Figure 1. Early Events during Sexual Transmission of HIV
From top to bottom: The epithelial lining of the vagina forms an efficient barrier to viral penetration when intact. Cervical mucus may serve to strengthen this barrier by physically trapping virions [ 25]. HIV crosses the epithelial barrier either because of epithelial damage (e.g., microabrasions and traumatic breaches or lesions caused by STDs), or capture by intra-epithelial DCs that convey the virus to target cells deeper in the mucosa [ 9]. In the lumen of the vagina, continuous with the cervical canal, virions with two kinds of tropism are illustrated: (i) X4 virus (orange) uses the co-receptor CXCR4 (rarely found early after transmission) and (ii) R5 virus (green) utilizing the co-receptor CCR5 (preferentially found early after transmission). Why R5 virus comes to dominate in the newly infected host is not known; it may reflect preferential amplification at a stage after transmission (not shown) [ 26]. To the left, an R5 virion is shown bound to an embedded DC, which has CD4, CCR5, and C-type lectin receptors on its surface, all of which can interact with the surface glycoprotein of the virus. The DC may merely capture X4 or R5 virus and carry it across the epithelial barrier or get infected by R5 virus and produce progeny virus (virus budding from the cell surface is shown as half-circular sections studded with grey Env spikes) [ 9]. To the right, an R5 virion binds to and infects a T helper lymphocyte, which has both CD4 and CCR5 on its surface. Virus that has penetrated into the epithelium is also shown to infect a macrophage. Arrows indicate how virus infects the first target cells and how progeny virus or DCs then migrate via the afferent lymphatics to reach the lymph nodes. Here, further amplification occurs in an environment rich in CD4 + target cells. From there, new generations of progeny virus cascade to the next level of lymphatic tissue. The gut-associated lymphoid tissue provides an important reservoir of susceptible cells that the virus rapidly decimates (not shown). Ultimately, the virus disseminates via efferent lymphatics and blood to spleen, brain, liver, and lungs. (Illustration: CourtesyIAVI Report, Volume 8, May–August 2004).

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Source: PubMed

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