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Zika virus infects human testicular tissue and germ cells
Giulia Matusali, … , Anna Le Tortorec, Nathalie Dejucq-Rainsford
Giulia Matusali, … , Anna Le Tortorec, Nathalie Dejucq-Rainsford
Published July 31, 2018
Citation Information: J Clin Invest. 2018;128(10):4697-4710. https://doi.org/10.1172/JCI121735.
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Research Article Virology

Zika virus infects human testicular tissue and germ cells

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Abstract

Zika virus (ZIKV) is a teratogenic mosquito-borne flavivirus that can be sexually transmitted from man to woman. The finding of high viral loads and prolonged viral shedding in semen suggests that ZIKV replicates within the human male genital tract, but its target organs are unknown. Using ex vivo infection of organotypic cultures, we demonstrated here that ZIKV replicates in human testicular tissue and infects a broad range of cell types, including germ cells, which we also identified as infected in semen from ZIKV-infected donors. ZIKV had no major deleterious effect on the morphology and hormonal production of the human testis explants. Infection induced a broad antiviral response but no IFN upregulation and minimal proinflammatory response in testis explants, with no cytopathic effect. Finally, we studied ZIKV infection in mouse testis and compared it to human infection. This study provides key insights into how ZIKV may persist in semen and alter semen parameters, as well as a valuable tool for testing antiviral agents.

Authors

Giulia Matusali, Laurent Houzet, Anne-Pascale Satie, Dominique Mahé, Florence Aubry, Thérèse Couderc, Julie Frouard, Salomé Bourgeau, Karim Bensalah, Sylvain Lavoué, Guillaume Joguet, Louis Bujan, André Cabié, Gleide Avelar, Marc Lecuit, Anna Le Tortorec, Nathalie Dejucq-Rainsford

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Figure 1

ZIKA virus replicates in human testicular tissue.

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ZIKA virus replicates in human testicular tissue.
Human testis explants ...
Human testis explants from 8 donors were ex vivo infected overnight with 105 TCID50 (corresponding to 2.2 × 107 to 2.9 × 107 vRNA copies) from a low-passage ZIKV strain isolated in 2015 in the French Caribbean (MRS_OPY_Martinique_PaRi-2015). Explants were thoroughly washed and cultured on inserts in 1 ml medium/well for 9 days, with media fully removed and changed every 3 days. Each of the time points (days 3, 6, 9) represents de novo viral release over a 3-day-culture period. (A) ZIKV RNA release over a 3-day culture period on days 3, 6, and 9 detected by RT-qPCR. (B) Viral titers determined by infectivity assay of 3-day culture period tissue supernatants on VeroE6 cells. Each symbol represents a different donor (same symbol/donor throughout the figures). Dotted lines represent the detection limit of the assays. Mock-infected explants were always below detection level. Bars represent median. *P < 0.05, **P < 0.01 (Friedman-Dunn nonparametric comparison).

Copyright © 2022 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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