Repeated Semen Exposure Increases Host Resistance to HIV Infection

Repeated semen exposure promotes resistance of the host to human immunodeficiency virus (HIV) infection, reports a new study, jointly conducted by the Wistar Institute and the University of Puerto Rico. The research team found that sustained exposure to semen, changes the characteristics of the immune cells present in the blood circulation and in vaginal tissue, as a result of which they become less susceptible to infection by HIV. This finding goes against the established view that semen promotes the transmission of HIV from men to women through vaginal intercourse.

The study findings, published in the journal Nature Communications, shed new light on why some prostitutes test negative for HIV, despite continuous high-risk vaginal intercourse.

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Study Team

The study was led by Dr. Luis J. Montaner, DVM, DPhil, who is the Vice President of Scientific Operations and the Herbert Kean, MD, Family Professor, and Director of the HIV-1 Immunopathogenesis Laboratory at the Wistar Institute, Philadelphia, PA, USA.

The research was co-directed by Dr. Edmundo N. Kraiselburd, PhD, who is a Professor and Director of the SNRP NeuroAIDS Research Program in the Department of Microbiology and Zoology at the University of Puerto Rico School of Medicine, San Juan, Puerto Rico. He supervised the non-human primate (NHP) model studies at the Caribbean Primate Research Center in Cayo Santiago, Puerto Rico.

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Study Background

The current research is based on a previous study conducted by Montaner’s Group in 2015. Their study revealed that continuous exposure to semen in prostitutes led to changes in the cervicovaginal tissue that predicted an increased resistance to HIV infection. The present study focused on whether semen played a direct role in resistance to HIV.

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Study Procedure

• The study was conducted in rhesus monkeys (Macaca mulatta)
• Simian immunodeficiency virus (SIV), which is similar to HIV but infects primates and produces a similar condition to AIDS, was used for infecting the monkeys
• The monkeys were divided into the following two groups:
• Group 1: Exposed to semen containing inactivated SIV particles twice a week for 20 weeks
• Group 2: Exposed to semen without SIV particles twice a week for 20 weeks
• After 20 weeks, the monkeys in both groups were challenged intravaginally with low-doses of SIV
• Specific markers of immune activation in the circulation and in cervicovaginal tissue were analyzed

Study Findings

• 42 percent decrease in the risk of infection was noted in semen-exposed monkeys
• Semen exposure resulted in lower expression of CCR5 on CD4⁺ T-cells, which acts as a receptor for attachment of HIV during infection
• Semen exposure resulted in higher expression of the CCL5 cytokine, which suppresses HIV
• Semen exposure resulted in increased levels of antiviral factors such as MX1 in the cervicovaginal tissue
• MX1 levels were correlated with the levels of interferon (IFN)-epsilon, which exhibits anti-HIV properties
• IFN-epsilon induction in cervicovaginal tissue is associated with unprotected vaginal intercourse
• Semen-exposed monkeys that remained uninfected upon low-dose SIV challenge became infected upon exposure to high-doses of SIV

Study Implications

The study findings indicate that despite repeated semen-exposure, the monkeys remained susceptible to infection, indicating that semen exposure only provides partial protection against HIV infection. Therefore, preventive methods such as pre-exposure prophylaxis (PrEP) and condoms should continue to be used for the prevention of HIV infection.

Concluding Remarks

“While HIV infection has been with us for more than 30 years, this is the first study that describes how semen exposure over time could result in local tissue changes that limit HIV infection in humans,” says Montaner.

“Apart from defining a new factor that may regulate HIV transmission, this unexpected finding could directly impact the design of future HIV vaccine studies that commonly recruit female sex workers. Currently, condom less intercourse is assumed only to promote the likelihood of infection. Our observation, however, raises the hypothesis that frequent semen exposure may potentially reduce HIV transmission.”

Kraiselburd concludes: “This research clearly shows the valuable information the macaque model can provide when used to study what may determine HIV infections in humans.”

Funding Source

The study was funded by the National Institutes of Health, the Robert I. Jacobs Fund of the Philadelphia Foundation, the Kean Family Professorship, the Penn Center for AIDS Research, the Duke Center for AIDS Research, and DFG (German Research Foundation). Besides these, core funding to the Wistar Institute was provided by the Cancer Center Support Grant (CCSG) from the National Cancer Institute, Bethesda, MD, USA.

Reference:

1. Repeated Semen Exposure Decreases Cervicovaginal SIVmac251 Infection in Rhesus Macaques - (https://www.nature.com/articles/s41467-019-11814-5)

Source-Medindia