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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 references12

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          Homeostatic regulation of the immune system by receptor tyrosine kinases of the Tyro 3 family.

          Q. Lu, G Lemke (2001)
          Receptor tyrosine kinases and their ligands mediate cell-cell communication and interaction in many organ systems, but have not been known to act in this capacity in the mature immune system. We now provide genetic evidence that three closely related receptor tyrosine kinases, Tyro 3, Axl, and Mer, play an essential immunoregulatory role. Mutant mice that lack these receptors develop a severe lymphoproliferative disorder accompanied by broad-spectrum autoimmunity. These phenotypes are cell nonautonomous with respect to lymphocytes and result from the hyperactivation of antigen-presenting cells in which the three receptors are normally expressed.
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            Zika virus infection complicated by Guillain-Barre syndrome--case report, French Polynesia, December 2013.

            Zika fever, considered as an emerging disease of arboviral origin, because of its expanding geographic area, is known as a benign infection usually presenting as an influenza-like illness with cutaneous rash. So far, Zika virus infection has never led to hospitalisation. We describe the first case of Guillain-Barré syndrome (GBS) occurring immediately after a Zika virus infection, during the current Zika and type 1 and 3 dengue fever co-epidemics in French Polynesia.
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              Zika virus infection complicated by Guillain-Barré syndrome – case report, French Polynesia, December 2013

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                Author and article information

                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
                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.

                Article
                NIHMS853329
                10.1038/nature20556
                5432198
                27798603
                9e419fb2-0128-4b08-9960-860a3fd9717f

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

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