HIV-1 in blood was found to be different from semen, the point of transmission.

The virus that causes AIDS may undergo changes in the genital tract rendering HIV-1 in semen different from HIV-1 in the blood, according to scientists from the University of North Carolina at Chapel Hill, the Edward Jenner Institute for Vaccine Research, and the Baylor Pediatric Center of Excellence. They note that their studies define different relationships between virus in blood and semen that could alter the composition of the viral population at the source that is most proximal to the transmitted virus.

The research appears in PLoS Pathogens, and the paper is titled “HIV-1 Populations in Semen Arise through Multiple Mechanisms.”

Most transmissions occur through sexual acts, making the virus in semen the proximal source in male donors. The nature of the virus in the male genital tract is of central importance to understanding the transmission process and the selective pressures that may impact the transmitted virus, the scientists explain.

The researchers examined the gene encoding the major surface protein of HIV-1, the Env protein, in viral populations in paired blood plasma and semen samples to determine any differences in the virus at the site of transmission, i.e., semen.

“In some men the virus population in semen was similar to that in the blood, suggesting that the virus was being imported from the blood into the genital tract and not being generated locally in the genital tract,” explains author Ronald Swanstrom, Ph.D., of the UNC Center for AIDS Research. “However, we found two mechanisms that significantly altered the virus population in the semen, showing that the virus can grow in the seminal tract in two different ways.”

In one way, one or more viruses grow rapidly in the seminal tract over a short period such that the viral population in semen is relatively homogeneous compared to the complex population in the blood. In the other way, the virus replicates in T cells in the seminal tract over a long period, creating a separate population of virus in semen that is both complex and distinct from the virus in the blood. The investigators thus propose that the viral populations in semen arise by multiple mechanisms including direct import of virus, oligoclonal amplification within the seminal tract, or compartmentalization.

In addition, they found significant enrichment of six out of nineteen cytokines and chemokines in semen of both HIV-infected and uninfected men and another seven further enriched in infected individuals. The enrichment of cytokines involved in innate immunity in the seminal tract, complemented with chemokines in infected men, creates an environment conducive to T-cell activation and viral replication.

“While it remains unknown how these differences change the biology of the virus or if these changes are important for the transmission process, it is clear that the virus in the blood does not always represent the virus at the site of transmission,” notes author Jeffrey Anderson.

“Making molecular clones of these compartmentalized viral env genes is an important next step that will allow us to study these differences,” adds Li-Hua Ping, another researcher involved in this study.

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