Human Testicular Germ Cells, a Reservoir for Zika Virus, Lack Antiviral Response Upon Zika or Poly(I:C) Exposure

Zika virus (ZIKV) is an emerging teratogenic arbovirus that persists in semen and is sexually transmitted. We previously demonstrated that ZIKV infects the human testis and persists in testicular germ cells (TGCs) for several months after patients’ recovery. To decipher the mechanisms underlying pro...

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Published in:	Frontiers in immunology Vol. 13; p. 909341
Main Authors:	Kuassivi, Ohiniba Nadège, Abiven, Hervé, Satie, Anne-Pascale, Cartron, Matéo, Mahé, Dominique, Aubry, Florence, Mathieu, Romain, Rebours, Valérie, Le Tortorec, Anna, Dejucq-Rainsford, Nathalie
Format:	Journal Article
Language:	English
Published:	Frontiers 17-06-2022 Frontiers Media S.A
Subjects:	human testis innate immunity Immunology interferon and antiviral effectors IRF3 Life Sciences pathogen recognition receptor (PRR) testicular germ cells Zika virus persistence RNA viruses pathogen recognition receptor (PRR) IRF3 interferon and antiviral effectors Poly(I:C) Zika virus persistence human testis innate immunity testicular germ cells
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Summary:	Zika virus (ZIKV) is an emerging teratogenic arbovirus that persists in semen and is sexually transmitted. We previously demonstrated that ZIKV infects the human testis and persists in testicular germ cells (TGCs) for several months after patients’ recovery. To decipher the mechanisms underlying prolonged ZIKV replication in TGCs, we compared the innate immune response of human testis explants and isolated TGCs to ZIKV and to Poly(I:C), a viral RNA analog. Our results demonstrate the weak innate responses of human testis to both ZIKV and Poly(I:C) as compared with other tissues or species. TGCs failed to up-regulate antiviral effectors and type I IFN upon ZIKV or Poly(I:C) stimulation, which might be due to a tight control of PRR signaling, as evidenced by the absence of activation of the downstream effector IRF3 and elevated expression of repressors. Importantly, exogenous IFNβ boosted the innate immunity of TGCs and inhibited ZIKV replication in the testis ex vivo , raising hopes for the prevention of ZIKV infection and persistence in this organ.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Edited by: Daishu Han, Chinese Academy of Medical Sciences and Peking Union Medical College, China These authors have contributed equally to this work This article was submitted to Viral Immunology, a section of the journal Frontiers in Immunology Reviewed by: Lucia Vojtech, University of Washington, United States; Monika Fijak, University of Giessen, Germany
ISSN:	1664-3224 1664-3224
DOI:	10.3389/fimmu.2022.909341