Semen inhibits Zika virus infection of cells and tissues from the anogenital region

Janis A Müller,Jan Münch,Franziska Krüger,Rüdiger Groß,Andrea Dietz ,Miriam Deniz,Markus Otto,Karen Jang ,Jens Von Einem,Jean-Philippe Herbeuval,Nathallie Sandi-Monroy,Jonas Schmidt‐Chanasit ,Olli Vapalahti,Simone Joas,Florian Ebner,Mirko Cortese,Benjamin Mayer,Axel Schubert,Nadia R Roan,Manuela Michel,Mirja Harms,Manuel Hayn,Ralf Bartenschlager,Sina Lippold

doi:10.1038/s41467-018-04442-y

Abstract

Zika virus (ZIKV) causes severe birth defects and can be transmitted via sexual intercourse. Semen from ZIKV-infected individuals contains high viral loads and may therefore serve as an important vector for virus transmission. Here we analyze the effect of semen on ZIKV infection of cells and tissues derived from the anogenital region. ZIKV replicates in all analyzed cell lines, primary cells, and endometrial or vaginal tissues. However, in the presence of semen, infection by ZIKV and other flaviviruses is potently inhibited. We show that semen prevents ZIKV attachment to target cells, and that an extracellular vesicle preparation from semen is responsible for this anti-ZIKV activity. Our findings suggest that ZIKV transmission is limited by semen. As such, semen appears to serve as a protector against sexual ZIKV transmission, despite the availability of highly susceptible cells in the anogenital tract and high viral loads in this bodily fluid.

Highlights

Zika virus (ZIKV) causes severe birth defects and can be transmitted via sexual intercourse
Primary endometrial and foreskin fibroblasts both supported efficient levels of ZIKV replication. These results demonstrate that ZIKV is capable of establishing productive infection in cells derived from the anogenital region
Considering the high viral titers in SE and our demonstration that cell lines, primary cells, and tissues derived from the anogenital region efficiently support productive ZIKV infection, it is surprising that the rates of sexual ZIKV transmission are low compared to mosquito-mediated transmission, where typically only 102 infectious virions are injected intravascularly[65,66]

Summary

Introduction

Zika virus (ZIKV) causes severe birth defects and can be transmitted via sexual intercourse. Semen (SE) from an infected individual can harbor ZIKV at extremely high concentrations of up to 108 viral RNA copies per ml[16,17,18,19,20] which are 4–5 log-fold higher than that present in serum, urine, and saliva, and the virus can remain detectable in SE >6 months after onset of symptoms[20,21,22,23] These observations have led to the notion that ZIKV in SE may be responsible for many cases of viral transmission[16,23,24,25,26,27,28]. The effect of SE and seminal amyloids on ZIKV infection has not yet been addressed[35,48] but could contribute to a better understanding of ZIKV as a sexually transmitted disease[30,49]

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Conclusion