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.

中文翻译：

---

人精液中果糖含量高，竞争性地抑制了针对高甘露糖聚糖的广泛而有效的抗病毒剂。

精液是各种病原病毒的主要传播媒介。传输的初始步骤，包括细胞附着和进入，可能在精液存在的情况下发生。但是，人类精浆的不稳定性质及其对培养细胞的毒性作用限制了在这种培养基中研究体外病毒感染和抑制的能力。我们发现，整个精液显着降低了针对HIV-1包膜糖蛋白（Envs）上的聚糖的抗体和杀微生物剂的效力。精液中过高的单糖果糖浓度可竞争性地抑制配体与Env上与α1,2-连接的甘露糖残基的结合，从而显着提高了效果。我们配制的稳定的精液合成模拟物可精确模拟整个人类精浆中的感染和抑制作用。我们的发现表明，除了生物分泌物的蛋白质含量外，它们的小溶质成分还会影响抗病毒杀微生物剂和粘膜抗体的效力。重要信息生物分泌物可使病毒在个体之间传播。每种类型的分泌物都有独特的蛋白质，盐和糖成分，会影响病毒的感染力并抑制该过程。在这里，我们描述了整个人类精浆中的HIV-1感染和抑制作用，以及我们制定的合成模拟物。我们发现精液中的果糖糖会降低针对甘露糖的HIV-1包膜蛋白的广泛有效的抗病毒剂的活性。精液果糖的这种作用可能会降低此类抑制剂预防HIV-1的性传播的功效。我们的发现表明，通过在模拟精液对HIV-1感染和抑制作用的合成制剂中进行体外评估，可以提高杀菌剂和疫苗引发的抗体的临床前评价。