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Persistence and clinical relevance of Zika virus in the male genital tract

Abstract

Zika virus (ZIKV) is a re-emerging mosquito-transmitted flavivirus associated with congenital abnormalities in newborns and with Guillain–Barré syndrome in adults. The virus can also be sexually transmitted and can persist in the male genital tract. Studies evaluating the kinetics of ZIKV in seminal shedding of men who have been infected, as well as in animal and cellular models of infection, have shown that, in addition to the testis and epididymis, the prostate and seminal vesicles could also be involved in persistent ZIKV infection. Additionally, some studies have reported that men infected with ZIKV can present with genitourinary symptoms such as haematospermia, prostatitis, painful ejaculation, penile discharge, and oligospermia; however, little is known about the effect of ZIKV on fertility. Understanding the mechanisms that underlie persistent ZIKV infections in men is crucial to developing guidelines, effective vaccines, and therapies.

Key points

  • Zika virus (ZIKV) is sexually transmitted and can induce male subfertility or infertility via multiple pathophysiological mechanisms.

  • ZIKV can impair sperm parameters and functions when localized in the male genital tract.

  • The role of ZIKV in the male genital tract remains unclear and further studies of ZIKV in semen and other male genital sites are required to determine the true effect of this pathogen on male fertility.

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Fig. 1: Schematic transmission cycles of ZIKV.
Fig. 2: Potential location of ZIKV infection in the male genital tract and its relationship with subfertility.
Fig. 3: Role of tyrosine-protein kinase receptors primarily expressed on the midpiece of human spermatozoa in ZIKV binding and entry into spermatozoa.
Fig. 4: Possibility of ZIKV interacting directly with spermatogenic cells and spermatozoa.

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Acknowledgements

This work was supported by grants from Coordenação de Aperfeiçoamento de Pessoal de Nível superior (CAPES), Brazilian Government.

Review criteria

The authors performed an extensive PubMed, MEDLINE, Web of Science and Scopus Scholar search for full-text papers and abstracts published in English, with no restrictions regarding to the initial date of publication up to April 2018. Search terms used were ‘Zika virus’ and ‘Zika virus infection’ plus ‘male infertility’, ‘fertility’, ‘infertility’, ‘semen’, ‘spermatozoa’, ‘testis’, ‘epididymis’, ‘seminal vesicles’, ‘prostate’, ‘seminiferous tubules’, ‘orchitis’, ‘prostatitis’, ‘urethritis’, ‘vasectomy’, ‘Sertoli cells’, ‘spermatogonia’, ‘Leydig cells’, ‘spermatogenesis’, ‘haematospermia’, ‘oligospermia’, ‘azoospermia’, ‘sperm motility’, ‘semen analysis’ and ‘cell culture techniques’. In addition, the reference lists of the selected papers were searched for additional relevant publications. Epidemiology bulletins from the US Centers for Disease Control and Prevention (CDC) were also included.

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F.A.K., C.S.S.M., G.M.Z.F.D., E.D., A.R.B.A.C., T.T.S. and M.E.L.C. wrote the manuscript. All authors researched data for the article, took part in discussions of content and wrote and edited the article before submission.

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Correspondence to Marcia E. L. Consolaro.

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Kurscheidt, F.A., Mesquita, C.S.S., Damke, G.M.Z.F. et al. Persistence and clinical relevance of Zika virus in the male genital tract. Nat Rev Urol 16, 211–230 (2019). https://doi.org/10.1038/s41585-019-0149-7

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