Testosterone Promotes the Intestinal Replication and Dissemination of Coxsackievirus B3 in an Oral Inoculation Mouse Model
Enteroviruses initiate infection in the gastrointestinal tract, and sex is often a biological variable that impacts pathogenesis. Previous data suggest that sex hormones can influence the intestinal replication of Coxsackievirus B3 (CVB3), an enterovirus in the family. However, the specific sex horm...
Gespeichert in:
Veröffentlicht in: | Journal of virology 2022-09, Vol.96 (17), p.e0123222-e0123222 |
---|---|
Hauptverfasser: | , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | e0123222 |
---|---|
container_issue | 17 |
container_start_page | e0123222 |
container_title | Journal of virology |
container_volume | 96 |
creator | Dhalech, Adeeba H Corn, Caleb M Mangale, Vrushali Syed, Fahim Condotta, Stephanie A Richer, Martin J Robinson, Christopher M |
description | Enteroviruses initiate infection in the gastrointestinal tract, and sex is often a biological variable that impacts pathogenesis. Previous data suggest that sex hormones can influence the intestinal replication of Coxsackievirus B3 (CVB3), an enterovirus in the
family. However, the specific sex hormone(s) that regulates intestinal CVB3 replication is poorly understood. To determine if testosterone promotes intestinal CVB3 replication, we orally inoculated male and female
mice that were treated with either placebo or testosterone-filled capsules. Following oral inoculation, we found that the testosterone-treated male and female mice shed significantly more CVB3 in their feces than did the placebo-treated mice, indicating that testosterone enhances intestinal replication. Similarly, testosterone enhanced viral dissemination in both sexes, as we observed higher viral loads in peripheral tissues following infection. Further, the testosterone-treated male mice also had a higher mortality rate than did the testosterone-depleted male mice. Finally, we observed that testosterone significantly affected the immune response to CVB3. We found that testosterone broadly increased proinflammatory cytokines and chemokines while decreasing the number of splenic B cells and dendritic cells following CVB3 infection. Moreover, while testosterone did not affect the early CD4 T cell response to CVB3, testosterone reduced the activation of CD8 T cells. These data indicate that testosterone can promote intestinal CVB3 replication and dissemination while also impacting the subsequent viral immune response.
Biological sex plays a significant role in the outcomes of various infections and diseases. The impact of sex hormones on the intestinal replication and dissemination of Coxsackievirus B3 remains poorly understood. Using an oral inoculation model, we found that testosterone enhances CVB3 shedding and dissemination in male and female mice. Further, testosterone can alter the immune response to CVB3. This work highlights the role of testosterone in CVB3 pathogenesis and suggests that sex hormones can impact the replication and dissemination of enteric viruses. |
doi_str_mv | 10.1128/jvi.01232-22 |
format | Article |
fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9472648</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2708259151</sourcerecordid><originalsourceid>FETCH-LOGICAL-a418t-9f2fdaeb47492e838ee89b63a1c22f08bcdebd6427fd90be6be5d8349aa9135e3</originalsourceid><addsrcrecordid>eNp1kU1v1DAQhi1U1C6lN87IxyKRYo-dxL4gtcvXSkVFqEjcLCeZtN4m9tZOVsCvx-2WCg5cPJbnmXc88xLygrMTzkG9WW_dCeMgoAB4QhacaVWUJZd7ZMEYQFEK9f2APEtpzRiXspL75EBUTNRSsQX5dYlpCmnCGDzSLzGMYcJEp2ukK59vk_N2oF9xM7jWTi54an1H37mUcMyp-5fQ02X4kWx743Dr4pzomaDujqQXMVevfGjnYcd-DnPCfHY4PCdPezskPHqIh-Tbh_eXy0_F-cXH1fL0vLCSq6nQPfSdxUbWUgMqoRCVbipheQvQM9W0HTZdJaHuO80arBosOyWktlZzUaI4JG93upu5GbFr0U_5V2YT3WjjTxOsM_9mvLs2V2FrtKyhkioLHD8IxHA7552Y0aUWh8F6zOMYqJmCUvOSZ_T1Dm1jSCli_9iGM3Nnl8l2mXu7DEDGX-1wm0Yw6zDHvO30P_bl32M8Cv_xUvwGuoGh1w</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2708259151</pqid></control><display><type>article</type><title>Testosterone Promotes the Intestinal Replication and Dissemination of Coxsackievirus B3 in an Oral Inoculation Mouse Model</title><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><creator>Dhalech, Adeeba H ; Corn, Caleb M ; Mangale, Vrushali ; Syed, Fahim ; Condotta, Stephanie A ; Richer, Martin J ; Robinson, Christopher M</creator><contributor>Schultz-Cherry, Stacey</contributor><creatorcontrib>Dhalech, Adeeba H ; Corn, Caleb M ; Mangale, Vrushali ; Syed, Fahim ; Condotta, Stephanie A ; Richer, Martin J ; Robinson, Christopher M ; Schultz-Cherry, Stacey</creatorcontrib><description>Enteroviruses initiate infection in the gastrointestinal tract, and sex is often a biological variable that impacts pathogenesis. Previous data suggest that sex hormones can influence the intestinal replication of Coxsackievirus B3 (CVB3), an enterovirus in the
family. However, the specific sex hormone(s) that regulates intestinal CVB3 replication is poorly understood. To determine if testosterone promotes intestinal CVB3 replication, we orally inoculated male and female
mice that were treated with either placebo or testosterone-filled capsules. Following oral inoculation, we found that the testosterone-treated male and female mice shed significantly more CVB3 in their feces than did the placebo-treated mice, indicating that testosterone enhances intestinal replication. Similarly, testosterone enhanced viral dissemination in both sexes, as we observed higher viral loads in peripheral tissues following infection. Further, the testosterone-treated male mice also had a higher mortality rate than did the testosterone-depleted male mice. Finally, we observed that testosterone significantly affected the immune response to CVB3. We found that testosterone broadly increased proinflammatory cytokines and chemokines while decreasing the number of splenic B cells and dendritic cells following CVB3 infection. Moreover, while testosterone did not affect the early CD4 T cell response to CVB3, testosterone reduced the activation of CD8 T cells. These data indicate that testosterone can promote intestinal CVB3 replication and dissemination while also impacting the subsequent viral immune response.
Biological sex plays a significant role in the outcomes of various infections and diseases. The impact of sex hormones on the intestinal replication and dissemination of Coxsackievirus B3 remains poorly understood. Using an oral inoculation model, we found that testosterone enhances CVB3 shedding and dissemination in male and female mice. Further, testosterone can alter the immune response to CVB3. This work highlights the role of testosterone in CVB3 pathogenesis and suggests that sex hormones can impact the replication and dissemination of enteric viruses.</description><identifier>ISSN: 0022-538X</identifier><identifier>EISSN: 1098-5514</identifier><identifier>DOI: 10.1128/jvi.01232-22</identifier><identifier>PMID: 36037480</identifier><language>eng</language><publisher>United States: American Society for Microbiology</publisher><subject>Animals ; Coxsackievirus Infections - immunology ; Coxsackievirus Infections - metabolism ; Coxsackievirus Infections - virology ; Disease Models, Animal ; Editor's Pick ; Female ; Host-Pathogen Interactions ; Male ; Mice ; Pathogenesis and Immunity ; Spotlight Selection ; Testosterone - metabolism ; Virology ; Virus Replication</subject><ispartof>Journal of virology, 2022-09, Vol.96 (17), p.e0123222-e0123222</ispartof><rights>Copyright © 2022 American Society for Microbiology.</rights><rights>Copyright © 2022 American Society for Microbiology. 2022 American Society for Microbiology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a418t-9f2fdaeb47492e838ee89b63a1c22f08bcdebd6427fd90be6be5d8349aa9135e3</citedby><cites>FETCH-LOGICAL-a418t-9f2fdaeb47492e838ee89b63a1c22f08bcdebd6427fd90be6be5d8349aa9135e3</cites><orcidid>0000-0003-4086-4690</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9472648/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9472648/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36037480$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Schultz-Cherry, Stacey</contributor><creatorcontrib>Dhalech, Adeeba H</creatorcontrib><creatorcontrib>Corn, Caleb M</creatorcontrib><creatorcontrib>Mangale, Vrushali</creatorcontrib><creatorcontrib>Syed, Fahim</creatorcontrib><creatorcontrib>Condotta, Stephanie A</creatorcontrib><creatorcontrib>Richer, Martin J</creatorcontrib><creatorcontrib>Robinson, Christopher M</creatorcontrib><title>Testosterone Promotes the Intestinal Replication and Dissemination of Coxsackievirus B3 in an Oral Inoculation Mouse Model</title><title>Journal of virology</title><addtitle>J Virol</addtitle><addtitle>J Virol</addtitle><description>Enteroviruses initiate infection in the gastrointestinal tract, and sex is often a biological variable that impacts pathogenesis. Previous data suggest that sex hormones can influence the intestinal replication of Coxsackievirus B3 (CVB3), an enterovirus in the
family. However, the specific sex hormone(s) that regulates intestinal CVB3 replication is poorly understood. To determine if testosterone promotes intestinal CVB3 replication, we orally inoculated male and female
mice that were treated with either placebo or testosterone-filled capsules. Following oral inoculation, we found that the testosterone-treated male and female mice shed significantly more CVB3 in their feces than did the placebo-treated mice, indicating that testosterone enhances intestinal replication. Similarly, testosterone enhanced viral dissemination in both sexes, as we observed higher viral loads in peripheral tissues following infection. Further, the testosterone-treated male mice also had a higher mortality rate than did the testosterone-depleted male mice. Finally, we observed that testosterone significantly affected the immune response to CVB3. We found that testosterone broadly increased proinflammatory cytokines and chemokines while decreasing the number of splenic B cells and dendritic cells following CVB3 infection. Moreover, while testosterone did not affect the early CD4 T cell response to CVB3, testosterone reduced the activation of CD8 T cells. These data indicate that testosterone can promote intestinal CVB3 replication and dissemination while also impacting the subsequent viral immune response.
Biological sex plays a significant role in the outcomes of various infections and diseases. The impact of sex hormones on the intestinal replication and dissemination of Coxsackievirus B3 remains poorly understood. Using an oral inoculation model, we found that testosterone enhances CVB3 shedding and dissemination in male and female mice. Further, testosterone can alter the immune response to CVB3. This work highlights the role of testosterone in CVB3 pathogenesis and suggests that sex hormones can impact the replication and dissemination of enteric viruses.</description><subject>Animals</subject><subject>Coxsackievirus Infections - immunology</subject><subject>Coxsackievirus Infections - metabolism</subject><subject>Coxsackievirus Infections - virology</subject><subject>Disease Models, Animal</subject><subject>Editor's Pick</subject><subject>Female</subject><subject>Host-Pathogen Interactions</subject><subject>Male</subject><subject>Mice</subject><subject>Pathogenesis and Immunity</subject><subject>Spotlight Selection</subject><subject>Testosterone - metabolism</subject><subject>Virology</subject><subject>Virus Replication</subject><issn>0022-538X</issn><issn>1098-5514</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kU1v1DAQhi1U1C6lN87IxyKRYo-dxL4gtcvXSkVFqEjcLCeZtN4m9tZOVsCvx-2WCg5cPJbnmXc88xLygrMTzkG9WW_dCeMgoAB4QhacaVWUJZd7ZMEYQFEK9f2APEtpzRiXspL75EBUTNRSsQX5dYlpCmnCGDzSLzGMYcJEp2ukK59vk_N2oF9xM7jWTi54an1H37mUcMyp-5fQ02X4kWx743Dr4pzomaDujqQXMVevfGjnYcd-DnPCfHY4PCdPezskPHqIh-Tbh_eXy0_F-cXH1fL0vLCSq6nQPfSdxUbWUgMqoRCVbipheQvQM9W0HTZdJaHuO80arBosOyWktlZzUaI4JG93upu5GbFr0U_5V2YT3WjjTxOsM_9mvLs2V2FrtKyhkioLHD8IxHA7552Y0aUWh8F6zOMYqJmCUvOSZ_T1Dm1jSCli_9iGM3Nnl8l2mXu7DEDGX-1wm0Yw6zDHvO30P_bl32M8Cv_xUvwGuoGh1w</recordid><startdate>20220914</startdate><enddate>20220914</enddate><creator>Dhalech, Adeeba H</creator><creator>Corn, Caleb M</creator><creator>Mangale, Vrushali</creator><creator>Syed, Fahim</creator><creator>Condotta, Stephanie A</creator><creator>Richer, Martin J</creator><creator>Robinson, Christopher M</creator><general>American Society for Microbiology</general><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>5PM</scope><orcidid>https://orcid.org/0000-0003-4086-4690</orcidid></search><sort><creationdate>20220914</creationdate><title>Testosterone Promotes the Intestinal Replication and Dissemination of Coxsackievirus B3 in an Oral Inoculation Mouse Model</title><author>Dhalech, Adeeba H ; Corn, Caleb M ; Mangale, Vrushali ; Syed, Fahim ; Condotta, Stephanie A ; Richer, Martin J ; Robinson, Christopher M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a418t-9f2fdaeb47492e838ee89b63a1c22f08bcdebd6427fd90be6be5d8349aa9135e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Animals</topic><topic>Coxsackievirus Infections - immunology</topic><topic>Coxsackievirus Infections - metabolism</topic><topic>Coxsackievirus Infections - virology</topic><topic>Disease Models, Animal</topic><topic>Editor's Pick</topic><topic>Female</topic><topic>Host-Pathogen Interactions</topic><topic>Male</topic><topic>Mice</topic><topic>Pathogenesis and Immunity</topic><topic>Spotlight Selection</topic><topic>Testosterone - metabolism</topic><topic>Virology</topic><topic>Virus Replication</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dhalech, Adeeba H</creatorcontrib><creatorcontrib>Corn, Caleb M</creatorcontrib><creatorcontrib>Mangale, Vrushali</creatorcontrib><creatorcontrib>Syed, Fahim</creatorcontrib><creatorcontrib>Condotta, Stephanie A</creatorcontrib><creatorcontrib>Richer, Martin J</creatorcontrib><creatorcontrib>Robinson, Christopher M</creatorcontrib><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>PubMed Central (Full Participant titles)</collection><jtitle>Journal of virology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dhalech, Adeeba H</au><au>Corn, Caleb M</au><au>Mangale, Vrushali</au><au>Syed, Fahim</au><au>Condotta, Stephanie A</au><au>Richer, Martin J</au><au>Robinson, Christopher M</au><au>Schultz-Cherry, Stacey</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Testosterone Promotes the Intestinal Replication and Dissemination of Coxsackievirus B3 in an Oral Inoculation Mouse Model</atitle><jtitle>Journal of virology</jtitle><stitle>J Virol</stitle><addtitle>J Virol</addtitle><date>2022-09-14</date><risdate>2022</risdate><volume>96</volume><issue>17</issue><spage>e0123222</spage><epage>e0123222</epage><pages>e0123222-e0123222</pages><issn>0022-538X</issn><eissn>1098-5514</eissn><abstract>Enteroviruses initiate infection in the gastrointestinal tract, and sex is often a biological variable that impacts pathogenesis. Previous data suggest that sex hormones can influence the intestinal replication of Coxsackievirus B3 (CVB3), an enterovirus in the
family. However, the specific sex hormone(s) that regulates intestinal CVB3 replication is poorly understood. To determine if testosterone promotes intestinal CVB3 replication, we orally inoculated male and female
mice that were treated with either placebo or testosterone-filled capsules. Following oral inoculation, we found that the testosterone-treated male and female mice shed significantly more CVB3 in their feces than did the placebo-treated mice, indicating that testosterone enhances intestinal replication. Similarly, testosterone enhanced viral dissemination in both sexes, as we observed higher viral loads in peripheral tissues following infection. Further, the testosterone-treated male mice also had a higher mortality rate than did the testosterone-depleted male mice. Finally, we observed that testosterone significantly affected the immune response to CVB3. We found that testosterone broadly increased proinflammatory cytokines and chemokines while decreasing the number of splenic B cells and dendritic cells following CVB3 infection. Moreover, while testosterone did not affect the early CD4 T cell response to CVB3, testosterone reduced the activation of CD8 T cells. These data indicate that testosterone can promote intestinal CVB3 replication and dissemination while also impacting the subsequent viral immune response.
Biological sex plays a significant role in the outcomes of various infections and diseases. The impact of sex hormones on the intestinal replication and dissemination of Coxsackievirus B3 remains poorly understood. Using an oral inoculation model, we found that testosterone enhances CVB3 shedding and dissemination in male and female mice. Further, testosterone can alter the immune response to CVB3. This work highlights the role of testosterone in CVB3 pathogenesis and suggests that sex hormones can impact the replication and dissemination of enteric viruses.</abstract><cop>United States</cop><pub>American Society for Microbiology</pub><pmid>36037480</pmid><doi>10.1128/jvi.01232-22</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0003-4086-4690</orcidid><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0022-538X |
ispartof | Journal of virology, 2022-09, Vol.96 (17), p.e0123222-e0123222 |
issn | 0022-538X 1098-5514 |
language | eng |
recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9472648 |
source | MEDLINE; EZB-FREE-00999 freely available EZB journals; PubMed Central |
subjects | Animals Coxsackievirus Infections - immunology Coxsackievirus Infections - metabolism Coxsackievirus Infections - virology Disease Models, Animal Editor's Pick Female Host-Pathogen Interactions Male Mice Pathogenesis and Immunity Spotlight Selection Testosterone - metabolism Virology Virus Replication |
title | Testosterone Promotes the Intestinal Replication and Dissemination of Coxsackievirus B3 in an Oral Inoculation Mouse Model |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-18T20%3A52%3A53IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Testosterone%20Promotes%20the%20Intestinal%20Replication%20and%20Dissemination%20of%20Coxsackievirus%20B3%20in%20an%20Oral%20Inoculation%20Mouse%20Model&rft.jtitle=Journal%20of%20virology&rft.au=Dhalech,%20Adeeba%20H&rft.date=2022-09-14&rft.volume=96&rft.issue=17&rft.spage=e0123222&rft.epage=e0123222&rft.pages=e0123222-e0123222&rft.issn=0022-538X&rft.eissn=1098-5514&rft_id=info:doi/10.1128/jvi.01232-22&rft_dat=%3Cproquest_pubme%3E2708259151%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2708259151&rft_id=info:pmid/36037480&rfr_iscdi=true |