2023-06-16 09:59:16
The human immunodeficiency virus (HIV-1) targets 3 types of immune system cells: T lymphocytes, monocytes and macrophages. Its entry into these cells involves the binding of the viral envelope glycoprotein gp120 to the CD4 receptor expressed on the cell surface. This binding leads to a change in the conformation of the glycoprotein which allows the virus to bind to two other membrane co-receptors expressed by the host cell: the CXCR4 or CCR5 receptors. These are then referred to respectively as X4 (HIV-X4) or R5 (HIV-R5) tropic strains of HIV. These two steps, binding to the main receptor and then to the coreceptor, are essential for the infection of the target cells.
Semen is the main vector for the sexual transmission of HIV-1 and both virus subtypes (X4 and R5) are found in the liquid fraction of semen, called seminal fluid. This liquid is composed of proteins, lipids, metabolites and very large quantities of small positively charged molecules: polyamines, mainly spermine and spermidine. Surprisingly, despite the concomitant presence of X4 and R5 viruses in seminal fluid, only HIV-R5 viruses are sexually transmitted. This is all the more surprising since the CXCR4 receptor is more widely expressed on the surface of HIV target cells than the CCR5 receptor. There is therefore an anti-HIV-X4 “barrier” which has still not been discovered.
To identify the factors likely to limit the sexual transmission of HIV-X4, a European collective of chemists and biologists, led by a team from the Laboratory of Pharmacological and Toxicological Chemistry and Biochemistry (CNRS/Université Paris Cité), generated a library of compounds derived from seminal fluid. They then assessed the anti-HIV effects of each fraction on HIV target cells. Of these, four flanking fractions blocked infection by HIV-X4 but not by HIV-R5. Analysis of these fractions revealed that they all contained polyamines, mainly spermine and spermidine. The study showed that spermine binds to the CXCR4 co-receptor, which has the effect of selectively blocking the infection of T lymphocytes and macrophages by HIV-X4. The spermine and spermidine contained in the seminal fluid therefore seem to be at the origin of the unsolved enigma for more than 40 years of the sexual transmission of viruses.
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