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 5

ZIKV infection ex vivo does not alter human testis explant morphology, cell viability, or hormonal production.

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ZIKV infection ex vivo does not alter human testis explant morphology, c...
(A) Toluidine histological staining of testis explants, shown here for mock- infected (left) and ZIKV-infected (right) testis explants on day 6 p.i. (B) Cleaved caspase-3 IHC to detect apoptotic cells in mock (left) and ZIKV-infected (right) testis explants, shown here for day 6 p.i. (C) LDH release in testis supernatant expressed as percent of mock-infected explants on the corresponding day of culture. (D) Immunofluorescence colabeling of peritubular (α-SMA) and Leydig (CYP11A1) cells, shown on tissue sections on day 6 p.i. for mock- (left) and ZIKV-infected (right) explants. Nuclei are stained in blue. (E and G) Testosterone and inhibin B release in testis supernatants expressed as percent of mock-infected explants on the corresponding day of culture. (F) Immunofluorescence labeling of Sertoli cell tight junction–associated protein ZO-1 in tissues sections for mock- (left) and ZIKV-infected (right) explants, shown on day 6 p.i. Nuclei are stained in blue. Scale bars: 50 μm. C, E, and G: each symbol represents a different donor; horizontal bars represent median values.