HIV-1 populations in semen arise through multiple mechanisms

Basic science

HIV-1 populations in semen arise through multiple mechanisms

HIV-1 is present in anatomical compartments and bodily fluids. Most transmissions occur through sexual acts, making virus in semen the proximal source in male donors. Anderson and colleagues find three distinct relationships in comparing viral RNA populations between blood and semen in men with chronic HIV-1 infection, and they 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 find 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. These studies define different relationships between virus in blood and semen that can significantly alter the composition of the viral population at the source that is most proximal to the transmitted virus.

Editors’ note: This groundbreaking work reveals that the disconnect sometimes observed between HIV-1 in blood plasma and semen is not just a quantitative one, e.g. undetectable viral load in plasma when virus is detectable in semen. It can also be a qualitative one, with different virus populations found in semen in some individuals. This study used single genome amplification to generate viral sequences from blood plasma and semen specimens from chronically infected men. In some men, the viral populations were the same, i.e. they were equilibrated as if they had been directly transferred from the blood. In others, there was evidence of clonal amplification, meaning that although the same sequences were seen as in the blood, their proportional representation was different suggesting that certain viral sequences had duplicated themselves in the semen. In yet others, there were viral sequences with no match in the blood – they were following a distinct evolutionary pathway. We need to better understand how immune modulators (cytokines and chemokines) may be shaping an environment that keeps activated target cells at the ready for HIV infection – this virus is one step ahead of us.