The Origins of Sexually Transmitted HIV Among Men Who Have Sex with Men

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Science Translational Medicine  10 Feb 2010:
Vol. 2, Issue 18, pp. 18re1
DOI: 10.1126/scitranslmed.3000447

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Starting at the Source

It is no mystery that the majority of HIV infections result from sexual transmission of virus, yet the cellular and molecular mechanisms involved are still poorly understood. The principal cell types in human semen are spermatozoa, immature germ cells, and white blood cells. HIV can potentially be carried in any of these or in the seminal fluid. Some men with acute HIV infection may be particularly contagious as a result of abnormally elevated HIV-associated white blood cells or high levels of HIV RNA in semen. Most quantitative studies of HIV in semen have used commercially available HIV RNA assays to measure copy numbers of cell-free virions in seminal plasma; only a few have used HIV DNA polymerase chain reaction assays to assess the prevalence or number of HIV-infected cells in semen. Even with these technological advances, it remains unclear whether transmitted strains originate as RNA virions or as integrated proviral DNA in infected seminal white blood cells.

The HIV-1 species in semen often differ genetically from those in the peripheral blood of the same infected person, and the genetic sequences of cell-free HIV in semen differ from those of cell-associated HIV in semen. It therefore should be possible to determine whether the initial transmission event is mediated by a cell-free virion or an HIV-infected cell. Mounting evidence from clinical, animal, and in vitro studies indicates that HIV-1–infected cells may be the critical vectors of transmission. However, the identification of the true source is complicated by the prevalence of cell-associated over cell-free HIV transmission, the risk factors associated with transmission, and the type and location of infected cells. In a search for the source reservoir of sexually transmitted HIV, Butler and colleagues examined the genetic and structural elements of a conserved genetic region of the viral envelope in blood- and semen-derived HIV RNA and DNA from source and recipient partners in six transmission pairs of men who have sex with men. In all transmission pairs, phylogenetic analyses revealed that viral sequences derived from the recipient partner’s blood plasma clustered with the sequences from his source partner’s seminal plasma rather than those from his seminal cells, providing compelling evidence for extracellular seminal HIV RNA as the source of infection. These seminal non–cell-associated RNA populations may represent a unique and tractable target to block transmission.


  • Citation: D. M. Butler, W. Delport, S. L. Kosakovsky Pond, M. K. Lakdawala, P. Man Cheng, S. J. Little, D. D. Richman, D. M. Smith, The Origins of Sexually Transmitted HIV Among Men Who Have Sex with Men. Sci. Transl. Med. 2, 18re1 (2010).

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