Epididymal epithelium propels early sexual transmission of Zika virus in the absence of interferon signaling

Alexander G. Pletnev, Olga A. Maximova, Guangping Liu, Heather Kenney, Bianca M. Nagata, Tatiana Zagorodnyaya, Ian Moore, Konstantin Chumakov and Konstantin A. Tsetsarkin ()
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Alexander G. Pletnev: National Institutes of Health
Olga A. Maximova: National Institutes of Health
Guangping Liu: National Institutes of Health
Heather Kenney: National Institutes of Health
Bianca M. Nagata: National Institutes of Health
Tatiana Zagorodnyaya: Center for Biologics Evaluation and Research, U.S. Food and Drug Administration
Ian Moore: National Institutes of Health
Konstantin Chumakov: Center for Biologics Evaluation and Research, U.S. Food and Drug Administration
Konstantin A. Tsetsarkin: National Institutes of Health

Nature Communications, 2021, vol. 12, issue 1, 1-16

Abstract: Abstract Recognition of Zika virus (ZIKV) sexual transmission (ST) among humans challenges our understanding of the maintenance of mosquito-borne viruses in nature. Here we dissected the relative contributions of the components of male reproductive system (MRS) during early male-to-female ZIKV transmission by utilizing mice with altered antiviral responses, in which ZIKV is provided an equal opportunity to be seeded in the MRS tissues. Using microRNA-targeted ZIKV clones engineered to abolish viral infectivity to different parts of the MRS or a library of ZIKV genomes with unique molecular identifiers, we pinpoint epithelial cells of the epididymis (rather than cells of the testis, vas deferens, prostate, or seminal vesicles) as a most likely source of the sexually transmitted ZIKV genomes during the early (most productive) phase of ZIKV shedding into the semen. Incorporation of this mechanistic knowledge into the development of a live-attenuated ZIKV vaccine restricts its ST potential.

Date: 2021
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DOI: 10.1038/s41467-021-22729-5

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