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Zika virus infection damages the testes in mice

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      Abstract

      Zika virus (ZIKV) infection of pregnant women can cause congenital malformations including microcephaly, which has focused global attention on this emerging pathogen 1 . In addition to transmission by mosquitoes, ZIKV can be detected in the seminal fluid of affected males for extended periods of time and transmitted sexually 2 . Here, using a mouse-adapted African ZIKV strain (Dakar 41519) we evaluated the consequences of infection in the male reproductive tract of mice. We observed persistence of ZIKV, but not the closely related Dengue virus (DENV), in the testis and epididymis of male mice, and this was associated with tissue injury that caused diminished testosterone and inhibin B levels, and oligospermia. ZIKV preferentially infected spermatogonia, primary spermatocytes, and Sertoli cells in the testis, resulting in cell death and destruction of the seminiferous tubules. Less damage was observed with a contemporary Asian ZIKV strain (H/PF/2013), in part because this virus replicates less efficiently in mice. The extent to which these observations in mice translate to humans remains unclear, but longitudinal studies of sperm function and viability in ZIKV-infected humans seem warranted.

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      Most cited references 36

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      Zika Virus Infection in Pregnant Women in Rio de Janeiro - Preliminary Report.

      Background Zika virus (ZIKV) has been linked to neonatal microcephaly. To characterize the spectrum of ZIKV disease in pregnancy, we followed patients in Rio de Janeiro to describe clinical manifestations in mothers and repercussions of acute ZIKV infection in fetuses. Methods We enrolled pregnant women in whom a rash had developed within the previous 5 days and tested blood and urine specimens for ZIKV by reverse-transcriptase-polymerase-chain-reaction assays. We followed the women prospectively and collected clinical and ultrasonographic data. Results A total of 88 women were enrolled from September 2015 through February 2016; of these 88 women, 72 (82%) tested positive for ZIKV in blood, urine, or both. The timing of acute ZIKV infection ranged from 5 to 38 weeks of gestation. Predominant clinical features included pruritic descending macular or maculopapular rash, arthralgias, conjunctival injection, and headache; 28% had fever (short-term and low-grade). Women who were positive for ZIKV were more likely than those who were negative for the virus to have maculopapular rash (44% vs. 12%, P=0.02), conjunctival involvement (58% vs. 13%, P=0.002), and lymphadenopathy (40% vs. 7%, P=0.02). Fetal ultrasonography was performed in 42 ZIKV-positive women (58%) and in all ZIKV-negative women. Fetal abnormalities were detected by Doppler ultrasonography in 12 of the 42 ZIKV-positive women (29%) and in none of the 16 ZIKV-negative women. Adverse findings included fetal deaths at 36 and 38 weeks of gestation (2 fetuses), in utero growth restriction with or without microcephaly (5 fetuses), ventricular calcifications or other central nervous system (CNS) lesions (7 fetuses), and abnormal amniotic fluid volume or cerebral or umbilical artery flow (7 fetuses). To date, 8 of the 42 women in whom fetal ultrasonography was performed have delivered their babies, and the ultrasonographic findings have been confirmed. Conclusions Despite mild clinical symptoms, ZIKV infection during pregnancy appears to be associated with grave outcomes, including fetal death, placental insufficiency, fetal growth restriction, and CNS injury.
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        Probable Non–Vector-borne Transmission of Zika Virus, Colorado, USA

        Clinical and serologic evidence indicate that 2 American scientists contracted Zika virus infections while working in Senegal in 2008. One of the scientists transmitted this arbovirus to his wife after his return home. Direct contact is implicated as the transmission route, most likely as a sexually transmitted infection.
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          Potential Sexual Transmission of Zika Virus

          In December 2013, during a Zika virus (ZIKV) outbreak in French Polynesia, a patient in Tahiti sought treatment for hematospermia, and ZIKV was isolated from his semen. ZIKV transmission by sexual intercourse has been previously suspected. This observation supports the possibility that ZIKV could be transmitted sexually.
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            Author and article information

            Affiliations
            [1 ]Departments of Medicine, The Center for Human Immunology, Washington University School of Medicine, Saint Louis, MO 63110 USA
            [2 ]Departments of Obstetrics and Gynecology, The Center for Human Immunology, Washington University School of Medicine, Saint Louis, MO 63110 USA
            [3 ]Departments of Pathology and Immunology, The Center for Human Immunology, Washington University School of Medicine, Saint Louis, MO 63110 USA
            [4 ]Departments of Molecular Microbiology, The Center for Human Immunology, Washington University School of Medicine, Saint Louis, MO 63110 USA
            [5 ]Departments of Cell Biology and Physiology, The Center for Human Immunology, Washington University School of Medicine, Saint Louis, MO 63110 USA
            [6 ]Departments of Immunotherapy Programs, Washington University School of Medicine, Saint Louis, MO 63110 USA
            Author notes
            [* ]Address correspondence to: Kelle Moley, M.D., Department of Obstetrics and Gynecology, Washington University School of Medicine, 425 South Euclid Avenue, St. Louis, MO 63110, USA. moleyk@ 123456wustl.edu , (314) 286-1775; Michael S. Diamond, M.D. Ph.D., Department of Medicine, Washington University School of Medicine, 660 South Euclid Ave. Box 8051, Saint Louis, MO 63110, USA. diamond@ 123456wusm.wustl.edu , (314) 362-2842
            [†]

            These authors contributed equally to the manuscript.

            Journal
            0410462
            6011
            Nature
            Nature
            Nature
            0028-0836
            1476-4687
            23 March 2017
            31 October 2016
            15 December 2016
            15 December 2017
            : 540
            : 7633
            : 438-442
            27798603 5432198 10.1038/nature20556 NIHMS853329

            Reprints and permissions information is available at www.nature.com/reprints;

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