Human CXCR4 Virus-Like Particles

Semen is an important vector for sexual transmission of HIV-1. Although CXCR4-tropic (X4) HIV-1 viruses may also be present in semen, almost exclusively CCR5-tropic (R5) HIV-1 viruses can cause systemic infection after sexual intercourse. To identify factors that may limit sexual transmission of X4-HIV-1, the researchers constructed a library of semen-derived compounds and screened them for antiviral drugs. They identified four adjacent components that blocked X4-HIV-1 but not R5-HIV-1, and found that they all contained polyamines abundant in semen, spermine and spermidine. The study found that spermine in semen at concentrations up to 14 mM could bind to CXCR4 and selectively inhibit cell-free and cell-associated infection of X4-HIV-1 viruses in cell lines and primary target cells at micromolar concentrations. These findings suggest that spermine in semen can inhibit sexual transmission of X4-HIV-1.

To experimentally demonstrate the interaction of spermine with CXCR4, the researchers used surface plasmon resonance (SPR) spectroscopy with the receptor immobilized on a sensor chip. Concentration-dependent binding of spermine to the receptor was found, with detection as low as 1 μM (Figure 1A and B). These results were confirmed by another SPR-based approach, in which virus-like particles expressing CXCR4 (VLP-CXCR4) were bound to biotinylated spermine immobilized on a streptavidin-coated sensor chip. Furthermore, preincubation of VLP-CXCR4 with different concentrations of free spermine for 15 minutes before injection resulted in a dose-dependent reduction in the binding of VLP-CXCR4 to biotinylated spermine (Figure 1C and D).

Figure 1. Spermine interacts with CXCR4 in surface plasmon resonance spectroscopy (SPR). (Harms M, et al., 2023)