IL-7 in Semen May Facilitate HIV Transmission during Vaginal Sex

The presence of the naturally occurring cytokine interleukin 7 (IL-7) in semen enhances HIV replication by stimulating CD4 T-cell replication, which may increase the likelihood of infection of the female genital tract during sex, according to a study published online February 7, 2013, in the open-access journal PLoS Pathogens.

Andrea Introini and colleagues from the Eunice Kennedy-Shriver National Institute of ChildHealth and Human Development looked at the effect of IL-7 on transmission of HIV in a laboratory study, finding that it significantly enhanced viral replication in infected cervical-vaginal and lymphoid tissue samples.

"The concentration of IL-7 in semen of HIV-1-infected men may be a key determinant of the efficiency of HIV-1 transmission to an uninfected female partner through vaginal intercourse," the study authors summarized.

Below is an edited excerpt from a National Institutes of Health press release describing the research and its findings in more detail.

Immune System Protein in Semen Boosts HIV Spread in Female Genital Tissue

NIH study suggests virus uses protein to spread

An immune system protein normally found in semen appears to enhance the spread of HIV to tissue from the uterine cervix, according to researchers at the National Institutes of Health. 

The protein interleukin 7 (IL-7) belongs to a family of proteins that regulate the immune response. IL-7 is present in normal semen, and occurs at especially high levels in the semen of men with HIV. 

The researchers developed a culture system of small pieces of tissue from the cervix and used this system to simulate male-to-female transmission of HIV, which causes AIDS. They observed the spread of the virus in cervical tissue under controlled laboratory conditions. In the presence of IL-7 at levels typically found in semen of men with HIV, the virus spreads to the tissue more readily than it spreads to tissue not treated with IL-7. 

According to the study authors, the finding raises the possibility that IL-7, alone or in combination with other molecules, can foster male-to-female transmission of HIV. Similarly, they note, it’s possible that the level of IL-7 in semen may determine how infectious a particular HIV-positive male is for a female sexual partner. Also, researchers may one day be able to prevent or delay the spread of HIV by blocking seminal IL-7.

The major targets for HIV infection are T cells, a type of immune cell that normally marshal the body’s defenses against disease-causing organisms.  Generally, when these cells become infected with HIV, they quickly die before the virus can produce a large number of copies of itself.  However, the researchers found that in isolated pieces of cervical tissue, HIV-infected T cells in the presence of IL-7 live longer and so continued to produce the virus. IL-7 also stimulated uninfected T cells to divide thus increasing their number. These new T-cells would provide additional targets for the virus, potentially increasing its spread.

Researchers have long known that biological interactions that take place in the laboratory may not always occur in the more complex environment of a living organism. For this reason, Dr. Margolis noted that additional studies would be needed to confirm what he and his coworkers observed in the laboratory.

"These experiments show us again how vicious HIV is," said senior author Leonid Margolis, PhD, head of the Section on Intercellular Interactions at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), where the research was conducted. "The virus is able to commandeer an immune protein for its own benefit."

The paper was co-authored by Andrea Introini, Christophe Vanpouille, PhD, Andrea Lisco, MD, PhD, Jean-Charles Grivel, PhD, and Leonid Margolis, PhD, all of the NICHD. Mr. Introini also is a PhD student at the University of Milan, Italy.

Their findings appear in PLOS Pathogens.

Based on their results with IL-7, Dr. Margolis said, his team plans to investigate whether other immune system proteins present in semen are involved in HIV transmission.

2/12/13

Reference

A Introini, C Vanpouille, A Lisco, et al. Interleukin-7 Facilitates HIV-1 Transmission to Cervico-Vaginal Tissue ex vivo. PLoS Pathogens 9(2):e1003148. February 7, 2013.

Other Source

Eunice Kennedy Shriver National Institute of Child Health and Human Development. Immune System Protein in Semen Boosts HIV Spread in Female Genital Tissue. NIH News press release. February 8, 2013.