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      Zika Virus in the Male Reproductive Tract

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          Abstract

          Arthropod-borne viruses (arboviruses) are resurging across the globe. Zika virus (ZIKV) has caused significant concern in recent years because it can lead to congenital malformations in babies and Guillain-Barré syndrome in adults. Unlike other arboviruses, ZIKV can be sexually transmitted and may persist in the male reproductive tract. There is limited information regarding the impact of ZIKV on male reproductive health and fertility. Understanding the mechanisms that underlie persistent ZIKV infections in men is critical to developing effective vaccines and therapies. Mouse and macaque models have begun to unravel the pathogenesis of ZIKV infection in the male reproductive tract, with the testes and prostate gland implicated as potential reservoirs for persistent ZIKV infection. Here, we summarize current knowledge regarding the pathogenesis of ZIKV in the male reproductive tract, the development of animal models to study ZIKV infection at this site, and prospects for vaccines and therapeutics against persistent ZIKV infection.

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          Rapid spread of emerging Zika virus in the Pacific area.

          D Musso, E.J. Nilles, V-M Cao-Lormeau (2014)
          Article 0 comments Cited 260 times – based on 0 reviews     Review now
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            Protective efficacy of multiple vaccine platforms against Zika virus challenge in rhesus monkeys.

            P Abbink, R. A. Larocca, R. A. De La Barrera … (2016)
            Zika virus (ZIKV) is responsible for a major ongoing epidemic in the Americas and has been causally associated with fetal microcephaly. The development of a safe and effective ZIKV vaccine is therefore an urgent global health priority. Here we demonstrate that three different vaccine platforms protect against ZIKV challenge in rhesus monkeys. A purified inactivated virus vaccine induced ZIKV-specific neutralizing antibodies and completely protected monkeys against ZIKV strains from both Brazil and Puerto Rico. Purified immunoglobulin from vaccinated monkeys also conferred passive protection in adoptive transfer studies. A plasmid DNA vaccine and a single-shot recombinant rhesus adenovirus serotype 52 vector vaccine, both expressing ZIKV premembrane and envelope, also elicited neutralizing antibodies and completely protected monkeys against ZIKV challenge. These data support the rapid clinical development of ZIKV vaccines for humans.
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              Zika virus cell tropism in the developing human brain and inhibition by azithromycin.

              Hanna Retallack, Elizabeth Di Lullo, Carolina Arias … (2016)
              The rapid spread of Zika virus (ZIKV) and its association with abnormal brain development constitute a global health emergency. Congenital ZIKV infection produces a range of mild to severe pathologies, including microcephaly. To understand the pathophysiology of ZIKV infection, we used models of the developing brain that faithfully recapitulate the tissue architecture in early to midgestation. We identify the brain cell populations that are most susceptible to ZIKV infection in primary human tissue, provide evidence for a mechanism of viral entry, and show that a commonly used antibiotic protects cultured brain cells by reducing viral proliferation. In the brain, ZIKV preferentially infected neural stem cells, astrocytes, oligodendrocyte precursor cells, and microglia, whereas neurons were less susceptible to infection. These findings suggest mechanisms for microcephaly and other pathologic features of infants with congenital ZIKV infection that are not explained by neural stem cell infection alone, such as calcifications in the cortical plate. Furthermore, we find that blocking the glia-enriched putative viral entry receptor AXL reduced ZIKV infection of astrocytes in vitro, and genetic knockdown of AXL in a glial cell line nearly abolished infection. Finally, we evaluate 2,177 compounds, focusing on drugs safe in pregnancy. We show that the macrolide antibiotic azithromycin reduced viral proliferation and virus-induced cytopathic effects in glial cell lines and human astrocytes. Our characterization of infection in the developing human brain clarifies the pathogenesis of congenital ZIKV infection and provides the basis for investigating possible therapeutic strategies to safely alleviate or prevent the most severe consequences of the epidemic.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Viruses
                Journal ID (iso-abbrev): Viruses
                Journal ID (publisher-id): viruses
                Title: Viruses
                Publisher: MDPI
                ISSN (Electronic): 1999-4915
                Publication date (Electronic): 16 April 2018
                Publication date Collection: April 2018
                Volume: 10
                Issue: 4
                Electronic Location Identifier: 198
                Affiliations
                Institute of Health and Biomedical Innovation, and School of Biomedical Sciences, Queensland University of Technology, Brisbane 4006, Queensland, Australia; liesel.stassen@ 123456qut.edu.au (L.S.); charles.armitage@ 123456qut.edu.au (C.W.A.); d.vanderheide@ 123456qut.edu.au (D.J.v.d.H.); k2.beagley@ 123456qut.edu.au (K.W.B.)
                Author notes
                [* ]Correspondence: francesca.frentiu@ 123456qut.edu.au ; Tel.: +61-731-386-185
                Author information
                https://orcid.org/0000-0001-9320-3963
                https://orcid.org/0000-0001-8628-4216
                Article
                Publisher ID: viruses-10-00198
                DOI: 10.3390/v10040198
                PMC ID: 5923492
                PubMed ID: 29659541
                SO-VID: f2f5ac9d-cbc3-4b09-be97-216a2ed6a579
                Copyright © © 2018 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 19 March 2018
                Date accepted : 13 April 2018
                Categories
                Subject: Review

                ScienceOpen disciplines: Microbiology & Virology
                Keywords: flavivirus,arbovirus,zika,sexual transmission,testis,prostate
                Data availability:
                ScienceOpen disciplines: Microbiology & Virology
                Keywords: flavivirus, arbovirus, zika, sexual transmission, testis, prostate

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