2023-07-05 20:00:14
A team of chemists and biologists from the National Center for Scientific Research (CNRS) in France, and from laboratories in Belgium and Germany have carried out a study which reveals that two abundant compounds in human semen, spermine and spermidinerestrict the sexual transmission of VIH-1 X4virus variants that use the CXCR4 coreceptor to enter target cells.
HIV-1 is the most common type of AIDS virus. According to the organization Avertabout 95% of people living with the virus have this type.
The findings could help explain why HIV-1 X4 variants are less prevalent in untreated patients and why these variants very rarely lead to systemic infection.
The findings of the work, now published in Science Advancescould help explain why HIV-1 X4 variants are less prevalent in untreated patients and why they very rarely lead to systemic infection.
Jean-Philippe Herbeuva, a chemistry, biology and immunology researcher at the CNRS and one of the study leaders, points out that “semen is the main vector of sexual transmission of HIV-1. The X4 and R5 virus subtypes They are found in the liquid fraction, known as seminal fluid.
Effect of semen polyamines during sexual infection by HIV. / Jean-Philippe Herbeuval and Nikaïa Smith CBMIT / CNRS
A molecular ‘gatekeeper’
This fluid is composed of proteins, lipids, metabolites and very high levels of small positively charged molecules called polyaminesmainly spermine and spermidine.
Surprisingly, adds Herbeuva, “despite the simultaneous presence of the X4 and R5 viruses in the seminal fluid, only the R5 are sexually transmitted. This is especially intriguing because the CXCR4 receptor is most widely expressed on the surface of cells. target cells of the AIDS virus than the CCR5 receptor”, he emphasizes.
The authors wondered about the existence of a possible ‘gatekeeper’ that would restrict infection by X4. To do this, they isolated molecules from the seminal plasma. They then evaluated the anti-HIV effects of each fraction on the target cells of the virus.
Our study demonstrated that spermine binds to the CXCR4 co-receptor, selectively blocking HIV-X4 infection of T lymphocytes and macrophages.
Jean-Philippe Herbeuva, study leader (CNRS)
Among them, explains the French researcher, “four adjacent fractions blocked the infection by X4 but not by R5.”
The analysis of these fractions “revealed that they all contained polyamines, mainly spermine and spermidine. Our study demonstrated that spermine binds to the CXCR4 co-receptor, selectively blocking HIV-X4 infection of T lymphocytes and macrophages.”
Therefore, he concludes, “spermine and spermidine, present in the seminal fluid, seem to be the origin of the unresolved mystery of the sexual transmission of the virus for more than 40 years.”
Reference:
Mirja Harms et al. “Spermine and spermidine bind CXCR4 and inhibit CXCR4- but not CCR5-tropic HIV-1 infection”. Science Advances (2023).
Rights: Creative Commons.
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