Natural Inhibitor of Human Cytomegalovirus in Human Seminal Plasma

Abstract

Human cytomegalovirus (HCMV) is the most frequent viral cause of congenital infections that can lead to severe birth defects. Although HCMV is frequently detected in semen and thus is potentially sexually transmitted, the role of semen in HCMV transmission is largely unclear. Here we describe that human seminal plasma (SP; the cell-free supernatant of semen) inhibits HCMV infection. The inhibition of HCMV infection was dose dependent and effective for different cell types, virus strains, and semen donors. This inhibitory effect was specific for HCMV, as herpes simplex virus 2 (HSV-2) and human immunodeficiency virus type 1 (HIV-1) infections were enhanced by SP. Mechanistically, SP inhibited infection by interfering with the attachment of virions to cells most likely via an interaction with the trimeric glycoprotein complex gH/gL/gO. Together, our findings suggest that semen contains a factor that potentially limits sexual transmission of HCMV. IMPORTANCE The role of semen in sexual transmission of human cytomegalovirus (HCMV) is currently unclear. This is surprising, as HCMV is frequently detected in this body fluid and infection is of high danger for neonates and pregnant women. In this study, we found that seminal plasma (SP) dose dependently inhibited HCMV infection. The infection inhibition was specific for HCMV, as other viruses, such as human immunodeficiency virus type 1 (HIV-1) and herpes simplex virus 2 (HSV-2), were not inhibited by SP. SP must contain a soluble, heat-resistant factor that limits attachment of HCMV particles to cells, probably by interaction with the trimeric glycoprotein complex gH/gL/gO. This novel virus-host interaction could possibly limit transmission of HCMV via semen during sexual intercourse.

Potent Restriction of Sexual Zika Virus Infection by the Lipid Fraction of Extracellular Vesicles in Semen

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From Ancient to Emerging Infections: The Odyssey of Viruses in the Male Genital Tract

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Current status of the COVID‐19 and male reproduction: A review of the literature

“…Human papillomavirus (HPV) was also found in most parts of the male reproductive system, including the testis, epididymis, ductus deferens, and semen 38‐40 . Finally, both cytomegalovirus (CMV) 41 and herpes simplex virus (HSV) 42 were detected in human spermatozoa. While CMV was found to have no impact on male reproductive health, HSV detection in the ejaculate was directly correlated with reduced sperm motility and normal morphology 43…”