The High Content of Fructose in Human Semen Competitively Inhibits Broad and Potent Antivirals That Target High-Mannose Glycans
| Autor: | Alicia M. Salvi, John Rosa, Kris A. DeMali, Jacklyn Johnson, Changze Han, Jennifer R Jagnow, Manuel G Flores, Hillel Haim, Amy E.T. Sparks |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
Male 0301 basic medicine Sexual transmission 030106 microbiology Immunology Mannose HIV Infections Semen Fructose Biology Antiviral Agents Genes env Microbiology 03 medical and health sciences chemistry.chemical_compound Anti-Infective Agents Polysaccharides Cell Line Tumor Virology Vaccines and Antiviral Agents Humans Infectivity chemistry.chemical_classification env Gene Products Human Immunodeficiency Virus Gene Products env In vitro Microbicides for sexually transmitted diseases HEK293 Cells 030104 developmental biology chemistry Biochemistry Insect Science HIV-1 Glycoprotein |
| Zdroj: | J Virol |
| ISSN: | 1098-5514 0022-538X |
| DOI: | 10.1128/jvi.01749-19 |
| Popis: | Semen is the primary transmission vehicle for various pathogenic viruses. Initial steps of transmission, including cell attachment and entry, likely occur in the presence of semen. However, the unstable nature of human seminal plasma and its toxic effects on cells in culture limit the ability to study in vitro virus infection and inhibition in this medium. We found that whole semen significantly reduces the potency of antibodies and microbicides that target glycans on the envelope glycoproteins (Envs) of HIV-1. The extraordinarily high concentration of the monosaccharide fructose in semen contributes significantly to the effect by competitively inhibiting the binding of ligands to α1,2-linked mannose residues on Env. Infection and inhibition in whole human seminal plasma are accurately mimicked by a stable synthetic simulant of seminal fluid that we formulated. Our findings indicate that, in addition to the protein content of biological secretions, their small-solute composition impacts the potency of antiviral microbicides and mucosal antibodies. IMPORTANCE Biological secretions allow viruses to spread between individuals. Each type of secretion has a unique composition of proteins, salts, and sugars, which can affect the infectivity potential of the virus and inhibition of this process. Here, we describe HIV-1 infection and inhibition in whole human seminal plasma and a synthetic simulant that we formulated. We discovered that the sugar fructose in semen decreases the activity of a broad and potent class of antiviral agents that target mannose sugars on the envelope protein of HIV-1. This effect of semen fructose likely reduces the efficacy of such inhibitors to prevent the sexual transmission of HIV-1. Our findings suggest that the preclinical evaluation of microbicides and vaccine-elicited antibodies will be improved by their in vitro assessment in synthetic formulations that simulate the effects of semen on HIV-1 infection and inhibition. |
| Databáze: | OpenAIRE |
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