Persistence of Zika virus RNA in the epididymis of the murine male reproductive tract
Zika virus (ZIKV) can infect developing fetuses in utero and cause severe congenital defects independent of route of maternal infection. Infected men can shed ZIKV RNA in semen for over six months. Whether prolonged viral RNA shedding in semen indicates a persistent infection in the male reproductiv...
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| Veröffentlicht in: | Virology (New York, N.Y.) N.Y.), 2021-08, Vol.560, p.43-53 |
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| creator | Vogt, Megan B. Frere, Francesca Hawks, Seth A. Perez, Claudia E. Coutermarsh-Ott, Sheryl Duggal, Nisha K. |
| description | Zika virus (ZIKV) can infect developing fetuses in utero and cause severe congenital defects independent of route of maternal infection. Infected men can shed ZIKV RNA in semen for over six months. Whether prolonged viral RNA shedding in semen indicates a persistent infection in the male reproductive tract is unknown. We hypothesized that if ZIKV establishes a persistent infection in the male reproductive tract (MRT), then immunosuppressant treatment should stimulate ZIKV replication and seminal shedding. Male mice were infected with ZIKV and immunosuppressed when they shed viral RNA but not infectious virus in ejaculates. Following immunosuppression, we did not detect infectious virus in ejaculates. However, we did detect ZIKV positive and negative sense RNA in the epididymal lumens of mice treated with cyclophosphamide, suggesting that ZIKV persists in the epididymis. This study provides insight into the mechanisms behind ZIKV sexual transmission, which may inform public health decisions regarding ZIKV risks.
•Zika virus persists in the epididymal lumen after virus is no longer shed in ejaculates.•Infectious Zika virus does not recrudesce following acute infection and immunosuppression.•Immunosuppression resulted in higher levels of ZIKV RNA in the epidiymides. |
| doi_str_mv | 10.1016/j.virol.2021.05.001 |
| format | Article |
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•Zika virus persists in the epididymal lumen after virus is no longer shed in ejaculates.•Infectious Zika virus does not recrudesce following acute infection and immunosuppression.•Immunosuppression resulted in higher levels of ZIKV RNA in the epidiymides.</description><identifier>ISSN: 0042-6822</identifier><identifier>EISSN: 1096-0341</identifier><identifier>DOI: 10.1016/j.virol.2021.05.001</identifier><identifier>PMID: 34023724</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Cell Line ; Chlorocebus aethiops ; chronic diseases ; cyclophosphamide ; Cyclophosphamide - pharmacology ; Epididymis ; Epididymis - virology ; Immune Tolerance - immunology ; Immunocompromised Host - immunology ; immunosuppression ; Immunosuppressive Agents - pharmacology ; Male ; Male reproductive tract ; males ; Mice ; Mice, Inbred C57BL ; Mouse model ; Persistent Infection - virology ; public health ; Recrudescence ; Recurrence ; RNA ; RNA, Viral - genetics ; RNA, Viral - isolation & purification ; Semen ; Semen - virology ; Sexual transmission ; Sexually Transmitted Diseases, Viral - transmission ; Vero Cells ; virology ; Virus Shedding - genetics ; viruses ; Zika virus ; Zika Virus - genetics ; Zika Virus - isolation & purification ; Zika Virus Infection - transmission</subject><ispartof>Virology (New York, N.Y.), 2021-08, Vol.560, p.43-53</ispartof><rights>2021 The Authors</rights><rights>Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c492t-79f9c983a083dda2d57da3c82867c3c942b0c2081ea85850ac2dd07bc61333fc3</citedby><cites>FETCH-LOGICAL-c492t-79f9c983a083dda2d57da3c82867c3c942b0c2081ea85850ac2dd07bc61333fc3</cites><orcidid>0000-0001-7385-3969 ; 0000-0002-9893-8069 ; 0000-0002-0186-843X ; 0000-0002-4520-3077</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.virol.2021.05.001$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,777,781,882,3537,27905,27906,45976</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34023724$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Vogt, Megan B.</creatorcontrib><creatorcontrib>Frere, Francesca</creatorcontrib><creatorcontrib>Hawks, Seth A.</creatorcontrib><creatorcontrib>Perez, Claudia E.</creatorcontrib><creatorcontrib>Coutermarsh-Ott, Sheryl</creatorcontrib><creatorcontrib>Duggal, Nisha K.</creatorcontrib><title>Persistence of Zika virus RNA in the epididymis of the murine male reproductive tract</title><title>Virology (New York, N.Y.)</title><addtitle>Virology</addtitle><description>Zika virus (ZIKV) can infect developing fetuses in utero and cause severe congenital defects independent of route of maternal infection. Infected men can shed ZIKV RNA in semen for over six months. Whether prolonged viral RNA shedding in semen indicates a persistent infection in the male reproductive tract is unknown. We hypothesized that if ZIKV establishes a persistent infection in the male reproductive tract (MRT), then immunosuppressant treatment should stimulate ZIKV replication and seminal shedding. Male mice were infected with ZIKV and immunosuppressed when they shed viral RNA but not infectious virus in ejaculates. Following immunosuppression, we did not detect infectious virus in ejaculates. However, we did detect ZIKV positive and negative sense RNA in the epididymal lumens of mice treated with cyclophosphamide, suggesting that ZIKV persists in the epididymis. This study provides insight into the mechanisms behind ZIKV sexual transmission, which may inform public health decisions regarding ZIKV risks.
•Zika virus persists in the epididymal lumen after virus is no longer shed in ejaculates.•Infectious Zika virus does not recrudesce following acute infection and immunosuppression.•Immunosuppression resulted in higher levels of ZIKV RNA in the epidiymides.</description><subject>Animals</subject><subject>Cell Line</subject><subject>Chlorocebus aethiops</subject><subject>chronic diseases</subject><subject>cyclophosphamide</subject><subject>Cyclophosphamide - pharmacology</subject><subject>Epididymis</subject><subject>Epididymis - virology</subject><subject>Immune Tolerance - immunology</subject><subject>Immunocompromised Host - immunology</subject><subject>immunosuppression</subject><subject>Immunosuppressive Agents - pharmacology</subject><subject>Male</subject><subject>Male reproductive tract</subject><subject>males</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mouse model</subject><subject>Persistent Infection - virology</subject><subject>public health</subject><subject>Recrudescence</subject><subject>Recurrence</subject><subject>RNA</subject><subject>RNA, Viral - genetics</subject><subject>RNA, Viral - isolation & purification</subject><subject>Semen</subject><subject>Semen - virology</subject><subject>Sexual transmission</subject><subject>Sexually Transmitted Diseases, Viral - transmission</subject><subject>Vero Cells</subject><subject>virology</subject><subject>Virus Shedding - genetics</subject><subject>viruses</subject><subject>Zika virus</subject><subject>Zika Virus - genetics</subject><subject>Zika Virus - isolation & purification</subject><subject>Zika Virus Infection - transmission</subject><issn>0042-6822</issn><issn>1096-0341</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkU1P3DAQhi3Uqiy0vwCp8rGXpOOPJM6BSghBqYRahODSi-W1J8VLNt7ayUr8-zosIHqpehrZ88w7Hy8hRwxKBqz-vCq3Poa-5MBZCVUJwPbIgkFbFyAke0MWAJIXteJ8nxyktIL8bhp4R_aFBC4aLhfk9gpj8mnEwSINHf3p7w3NulOi199PqB_oeIcUN95597D2aWbmn_UU_ZCD6ZFG3MTgJjv6LdIxGju-J2870yf88BQPye352c3pRXH54-u305PLwsqWj0XTdq1tlTCghHOGu6pxRljFVd1YYVvJl2A5KIZGVaoCY7lz0CxtzYQQnRWH5MtOdzMt1-gsDrl9rzfRr0180MF4_Xdm8Hf6V9hqxaEGybLApyeBGH5PmEadd7TY92bAMCXNqyqfV7aq_Q9UsEqKPGhGxQ61MaQUsXuZiIGevdMr_eidnr3TUOnsXa76-HqZl5pnszJwvAMwn3TrMepk_Wyc8xHtqF3w_2zwB0d0rHk</recordid><startdate>20210801</startdate><enddate>20210801</enddate><creator>Vogt, Megan B.</creator><creator>Frere, Francesca</creator><creator>Hawks, Seth A.</creator><creator>Perez, Claudia E.</creator><creator>Coutermarsh-Ott, Sheryl</creator><creator>Duggal, Nisha K.</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7S9</scope><scope>L.6</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-7385-3969</orcidid><orcidid>https://orcid.org/0000-0002-9893-8069</orcidid><orcidid>https://orcid.org/0000-0002-0186-843X</orcidid><orcidid>https://orcid.org/0000-0002-4520-3077</orcidid></search><sort><creationdate>20210801</creationdate><title>Persistence of Zika virus RNA in the epididymis of the murine male reproductive tract</title><author>Vogt, Megan B. ; Frere, Francesca ; Hawks, Seth A. ; Perez, Claudia E. ; Coutermarsh-Ott, Sheryl ; Duggal, Nisha K.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c492t-79f9c983a083dda2d57da3c82867c3c942b0c2081ea85850ac2dd07bc61333fc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Animals</topic><topic>Cell Line</topic><topic>Chlorocebus aethiops</topic><topic>chronic diseases</topic><topic>cyclophosphamide</topic><topic>Cyclophosphamide - pharmacology</topic><topic>Epididymis</topic><topic>Epididymis - virology</topic><topic>Immune Tolerance - immunology</topic><topic>Immunocompromised Host - immunology</topic><topic>immunosuppression</topic><topic>Immunosuppressive Agents - pharmacology</topic><topic>Male</topic><topic>Male reproductive tract</topic><topic>males</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mouse model</topic><topic>Persistent Infection - virology</topic><topic>public health</topic><topic>Recrudescence</topic><topic>Recurrence</topic><topic>RNA</topic><topic>RNA, Viral - genetics</topic><topic>RNA, Viral - isolation & purification</topic><topic>Semen</topic><topic>Semen - virology</topic><topic>Sexual transmission</topic><topic>Sexually Transmitted Diseases, Viral - transmission</topic><topic>Vero Cells</topic><topic>virology</topic><topic>Virus Shedding - genetics</topic><topic>viruses</topic><topic>Zika virus</topic><topic>Zika Virus - genetics</topic><topic>Zika Virus - isolation & purification</topic><topic>Zika Virus Infection - transmission</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Vogt, Megan B.</creatorcontrib><creatorcontrib>Frere, Francesca</creatorcontrib><creatorcontrib>Hawks, Seth A.</creatorcontrib><creatorcontrib>Perez, Claudia E.</creatorcontrib><creatorcontrib>Coutermarsh-Ott, Sheryl</creatorcontrib><creatorcontrib>Duggal, Nisha K.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Virology (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Vogt, Megan B.</au><au>Frere, Francesca</au><au>Hawks, Seth A.</au><au>Perez, Claudia E.</au><au>Coutermarsh-Ott, Sheryl</au><au>Duggal, Nisha K.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Persistence of Zika virus RNA in the epididymis of the murine male reproductive tract</atitle><jtitle>Virology (New York, N.Y.)</jtitle><addtitle>Virology</addtitle><date>2021-08-01</date><risdate>2021</risdate><volume>560</volume><spage>43</spage><epage>53</epage><pages>43-53</pages><issn>0042-6822</issn><eissn>1096-0341</eissn><abstract>Zika virus (ZIKV) can infect developing fetuses in utero and cause severe congenital defects independent of route of maternal infection. Infected men can shed ZIKV RNA in semen for over six months. Whether prolonged viral RNA shedding in semen indicates a persistent infection in the male reproductive tract is unknown. We hypothesized that if ZIKV establishes a persistent infection in the male reproductive tract (MRT), then immunosuppressant treatment should stimulate ZIKV replication and seminal shedding. Male mice were infected with ZIKV and immunosuppressed when they shed viral RNA but not infectious virus in ejaculates. Following immunosuppression, we did not detect infectious virus in ejaculates. However, we did detect ZIKV positive and negative sense RNA in the epididymal lumens of mice treated with cyclophosphamide, suggesting that ZIKV persists in the epididymis. This study provides insight into the mechanisms behind ZIKV sexual transmission, which may inform public health decisions regarding ZIKV risks.
•Zika virus persists in the epididymal lumen after virus is no longer shed in ejaculates.•Infectious Zika virus does not recrudesce following acute infection and immunosuppression.•Immunosuppression resulted in higher levels of ZIKV RNA in the epidiymides.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>34023724</pmid><doi>10.1016/j.virol.2021.05.001</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0001-7385-3969</orcidid><orcidid>https://orcid.org/0000-0002-9893-8069</orcidid><orcidid>https://orcid.org/0000-0002-0186-843X</orcidid><orcidid>https://orcid.org/0000-0002-4520-3077</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; ScienceDirect Journals (5 years ago - present) |
| subjects | Animals Cell Line Chlorocebus aethiops chronic diseases cyclophosphamide Cyclophosphamide - pharmacology Epididymis Epididymis - virology Immune Tolerance - immunology Immunocompromised Host - immunology immunosuppression Immunosuppressive Agents - pharmacology Male Male reproductive tract males Mice Mice, Inbred C57BL Mouse model Persistent Infection - virology public health Recrudescence Recurrence RNA RNA, Viral - genetics RNA, Viral - isolation & purification Semen Semen - virology Sexual transmission Sexually Transmitted Diseases, Viral - transmission Vero Cells virology Virus Shedding - genetics viruses Zika virus Zika Virus - genetics Zika Virus - isolation & purification Zika Virus Infection - transmission |
| title | Persistence of Zika virus RNA in the epididymis of the murine male reproductive tract |
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