Seminal Change

HIV might undergo changes in the genital tract that make the HIV-1 strain in semen different from what it is when it's in the bloodstream, according to a study led by researchers from the University of North Carolina at Chapel Hill. Worldwide, much of the transmission of HIV-1 is through sexual contact, men being the transmitting partner in the majority of cases. The new findings are significant because the nature of the virus in the male genital tract is of central importance to understanding the transmission process and the selective pressures that might affect the transmitted virus. Ultimately, it is the transmitted virus that must be blocked by a vaccine or microbicide. 'If everything we know about HIV is based on the virus that is in the blood'when in fact the virus in the semen can evolve to be different'it may be that we have an incomplete view of what is going on in the transmission of the virus,' says Ronald Swanstrom, Ph.D., a professor of biochemistry and biophysics and of microbiology and immunology at the UNC School of Medicine. In the study, published in August in the online journal PLoS Pathogens, Swanstrom and his colleagues compared viral populations in blood and semen samples collected from 16 men with chronic HIV-1 infection. Using single genome sequencing, they analyzed the gene coding for the major env protein, located on the surface of the virus, in the samples. The differences between the viruses from the two sources were striking, Swanstrom says. 'The sequence differences between the blood and the semen were like a flashing red light; it was a big hint about the biology of virus in the seminal tract,' he explains. 'In some men the virus population in semen was similar to that in the blood, suggesting that virus was being imported from the blood into the genital tract and not being generated locally in the genital tract. However, we found two mechanisms that significantly altered the virus population in the semen, showing that virus can grow in the seminal tract in two different ways.' In the first, he says, one to several viruses are rapidly expanded over a short period of time so that the viral population is relatively homogeneous compared to the complex population in the blood. In the second the virus replicates in T cells in the seminal tract over a long period of time, creating a separate population of virus that is both complex and distinct from the virus in the blood. To find out why these mechanisms are at play, the researchers then measured the levels of 19 cytokines and chemokines'proteins secreted by cells that control the immune system'in both the blood and semen samples. They discovered a significant concentration of these immune-system modulators in the semen relative to the blood, which could boost viral replication by creating an environment where target cells are kept in an activated state. Swanstrom's laboratory is now exploring whether evolutionary selection for some special property of the virus is occurring in the seminal tract that does not happen in the blood. 'While [we don't know] how these differences change the biology of the virus or if these changes are important for the transmission process,' study author Jeffrey Anderson says, 'it is clear that the virus in the blood does not always represent the virus at the site of transmission.' Knowing how the virus in the semen is different, the researchers say, could be an important part of understanding the puzzle of how HIV is transmitted.