Spermine and spermidine bind CXCR4 and inhibit CXCR4- but not CCR5-tropic HIV-1 infection
Mirja Harms1, Nikaïa Smith1,2,3, Mingyu Han3
1Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany.
Insights
Semen contains spermine, a compound that blocks CXCR4-tropic (X4) HIV-1 infection. This finding suggests that seminal spermine naturally restricts sexual transmission of X4 HIV-1, while not affecting CCR5-tropic (R5) HIV-1.
Area of Science:
- Virology
- Immunology
- Biochemistry
Background:
- Semen is a primary vector for sexual HIV-1 transmission.
- CCR5-tropic (R5) HIV-1 typically causes systemic infection, while CXCR4-tropic (X4) HIV-1 is less common in systemic infections post-transmission.
- Factors limiting X4 HIV-1 sexual transmission are not fully understood.
Purpose of the Study:
- To identify compounds in seminal fluid that inhibit sexual HIV-1 transmission.
- To investigate the differential effects of seminal compounds on X4 and R5 HIV-1 strains.
Main Methods:
- Generation and screening of a seminal fluid-derived compound library for antiviral activity.
- Identification of active fractions containing polyamines, specifically spermine and spermidine.
- Assays to determine the inhibitory effects of spermine on cell-free and cell-associated X4 and R5 HIV-1 infection.
Main Results:
- Four fractions blocked X4 HIV-1 but not R5 HIV-1 infection.
- These active fractions were found to contain spermine and spermidine.
- Spermine, present in semen at high concentrations (up to 14 mM), binds CXCR4 and selectively inhibits X4 HIV-1 infection at micromolar concentrations.
Conclusions:
- Seminal fluid contains factors that can restrict HIV-1 transmission.
- Spermine is identified as a key component that selectively inhibits X4 HIV-1 infection.
- Seminal spermine likely plays a role in limiting sexual transmission of X4 HIV-1.
Abstract:
Semen is an important vector for sexual HIV-1 transmission. Although CXCR4-tropic (X4) HIV-1 may be present in semen, almost exclusively CCR5-tropic (R5) HIV-1 causes systemic infection after sexual intercourse. To identify factors that may limit sexual X4-HIV-1 transmission, we generated a seminal fluid-derived compound library and screened it for antiviral agents. We identified four adjacent fractions that blocked X4-HIV-1 but not R5-HIV-1 and found that they all contained spermine and spermidine, abundant polyamines in semen. We showed that spermine, which is present in semen at concentrations up to 14 mM, binds CXCR4 and selectively inhibits cell-free and cell-associated X4-HIV-1 infection of cell lines and primary target cells at micromolar concentrations. Our findings suggest that seminal spermine restricts sexual X4-HIV-1 transmission.
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