Journal article
The High Content of Fructose in Human Semen Competitively Inhibits Broad and Potent Antivirals That Target High-Mannose Glycans
Journal of virology, Vol.94(9), e01749-19
05/01/2020
DOI: 10.1128/JVI.01749-19
PMCID: PMC7163146
PMID: 32102878
Abstract
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 alpha 1,2-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.
Details
- Title: Subtitle
- The High Content of Fructose in Human Semen Competitively Inhibits Broad and Potent Antivirals That Target High-Mannose Glycans
- Creators
- Jacklyn Johnson - Roy J. and Lucille A. Carver College of MedicineManuel G. Flores - Roy J. and Lucille A. Carver College of MedicineJohn Rosa - Roy J. and Lucille A. Carver College of MedicineChangze Han - Roy J. and Lucille A. Carver College of MedicineAlicia M. Salvi - Roy J. and Lucille A. Carver College of MedicineKris A. DeMali - Roy J. and Lucille A. Carver College of MedicineJennifer R. Jagnow - University of Iowa Hospitals and ClinicsAmy Sparks - Univ Iowa Hosp & Clin, In Vitro Fertilizat & Reprod Testing Lab, Iowa City, IA 52242 USAHillel Haim - Roy J. and Lucille A. Carver College of Medicine
- Resource Type
- Journal article
- Publication Details
- Journal of virology, Vol.94(9), e01749-19
- Publisher
- Amer Soc Microbiology
- DOI
- 10.1128/JVI.01749-19
- PMID
- 32102878
- PMCID
- PMC7163146
- ISSN
- 0022-538X
- eISSN
- 1098-5514
- Number of pages
- 22
- Grant note
- UIRF ICE Fund Award NIH T32 AI007533-17 / NIH Graduate Student Training Program Fellowship in Virology; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 05/01/2020
- Academic Unit
- Dermatology; Microbiology and Immunology; Obstetrics and Gynecology; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology
- Record Identifier
- 9984288718602771
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