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

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 6

ZIKV triggers a broad antiviral response but no IFN upregulation and a minimal proinflammatory response in human testicular tissue.

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ZIKV triggers a broad antiviral response but no IFN upregulation and a m...
(A) Levels of IFN-β and CXCL10 measured by flow cytometry–based multiplex assay in mock-infected and ZIKV-infected human testis explant supernatants. Each symbol represents a different donor. Bars represent median values. *P < 0.05 (Friedman-Dunn nonparametric comparison). (B) Correlation between secreted CXCL10 induction in ZIKV-infected versus mock-infected explants and ZIKV RNA level in culture supernatant on day 6 p.i. (Spearman’s nonparametric test). (C) Innate immune gene expression determined by RT-qPCR in testis explants from 6 donors (T1–T6) infected with ZIKV for 3, 6, and 9 days (d3, d6, d9). Heatmap shows log2-transformed expression ratios between ZIKV-infected and time-matched mock-infected controls. Green indicates upregulation and red downregulation of mRNA compared with controls. Type I and II IFN mRNAs were below the quantification threshold (data not shown). (D) Viral loads in supernatants of the testis explants analyzed in C. (E) Examples of correlation between gene fold expression on day 9 and the level of infection on day 3 p.i. (Spearman’s nonparametric test). Other correlations are shown in Supplemental Figure 9.