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Japanese encephalitis virus persists in the human reproductive epithelium and porcine reproductive tissues

Japanese encephalitis virus (JEV) is the emerging and geographically expanding flavivirus and the major causative agent of encephalitis in humans in Asia. There are risks of JEV introduction into the Americas given a large population of amplifying hosts—pigs and wild boars, and insect vectors—Culex...

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Autores principales: Chapagain, Subash, Pal Singh, Prince, Le, Khanh, Safronetz, David, Wood, Heidi, Karniychuk, Uladzimir
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9337681/
https://www.ncbi.nlm.nih.gov/pubmed/35905074
http://dx.doi.org/10.1371/journal.pntd.0010656
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author Chapagain, Subash
Pal Singh, Prince
Le, Khanh
Safronetz, David
Wood, Heidi
Karniychuk, Uladzimir
author_facet Chapagain, Subash
Pal Singh, Prince
Le, Khanh
Safronetz, David
Wood, Heidi
Karniychuk, Uladzimir
author_sort Chapagain, Subash
collection PubMed
description Japanese encephalitis virus (JEV) is the emerging and geographically expanding flavivirus and the major causative agent of encephalitis in humans in Asia. There are risks of JEV introduction into the Americas given a large population of amplifying hosts—pigs and wild boars, and insect vectors—Culex mosquitoes. There are emerging concerns about vector-free ways of flavivirus transmission, for example sexual and transplacental Zika virus transmissions, which may change flavivirus epidemiology and expand the geographical range to territories with no insect vectors. It is unknown whether JEV has tropism in the female lower reproductive tract and the potential for sexual transmission in humans. While clinical outcomes of transplacental JEV infection are described in humans and pigs, cellular targets and tissue tropism in the upper reproductive tract are also unknown. Here, we studied JEV infection phenotypes and host transcriptional responses in human reproductive epithelial cells. We found that JEV caused persistent infection and cytopathology in the vaginal epithelium, endometrial epithelium, and trophoblast. Human vaginal epithelial cells infected with JEV had altered transcriptional responses associated with inflammation and disruption of epithelial barrier function. Also, using pigs—the native amplifying host for JEV, we confirmed JEV tropism in the female lower and upper reproductive tracts. We discovered that JEV persists in the vaginal mucosa for at least 28 days and pigs shed the virus in vaginal secretions. We also found JEV persistence in the endometrium and placenta with transplacental and fetal infections. Altogether, we discovered that JEV targets the vaginal epithelium and has the potential for sexual transmission in humans. We also contributed to a better understanding of JEV pathogenesis during transplacental infection. Further studies are needed to better understand the interactions of JEV with reproductive tissues, how persistent infection affects female reproductive functions, and the risks for non-vector transmission.
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spelling pubmed-93376812022-07-30 Japanese encephalitis virus persists in the human reproductive epithelium and porcine reproductive tissues Chapagain, Subash Pal Singh, Prince Le, Khanh Safronetz, David Wood, Heidi Karniychuk, Uladzimir PLoS Negl Trop Dis Research Article Japanese encephalitis virus (JEV) is the emerging and geographically expanding flavivirus and the major causative agent of encephalitis in humans in Asia. There are risks of JEV introduction into the Americas given a large population of amplifying hosts—pigs and wild boars, and insect vectors—Culex mosquitoes. There are emerging concerns about vector-free ways of flavivirus transmission, for example sexual and transplacental Zika virus transmissions, which may change flavivirus epidemiology and expand the geographical range to territories with no insect vectors. It is unknown whether JEV has tropism in the female lower reproductive tract and the potential for sexual transmission in humans. While clinical outcomes of transplacental JEV infection are described in humans and pigs, cellular targets and tissue tropism in the upper reproductive tract are also unknown. Here, we studied JEV infection phenotypes and host transcriptional responses in human reproductive epithelial cells. We found that JEV caused persistent infection and cytopathology in the vaginal epithelium, endometrial epithelium, and trophoblast. Human vaginal epithelial cells infected with JEV had altered transcriptional responses associated with inflammation and disruption of epithelial barrier function. Also, using pigs—the native amplifying host for JEV, we confirmed JEV tropism in the female lower and upper reproductive tracts. We discovered that JEV persists in the vaginal mucosa for at least 28 days and pigs shed the virus in vaginal secretions. We also found JEV persistence in the endometrium and placenta with transplacental and fetal infections. Altogether, we discovered that JEV targets the vaginal epithelium and has the potential for sexual transmission in humans. We also contributed to a better understanding of JEV pathogenesis during transplacental infection. Further studies are needed to better understand the interactions of JEV with reproductive tissues, how persistent infection affects female reproductive functions, and the risks for non-vector transmission. Public Library of Science 2022-07-29 /pmc/articles/PMC9337681/ /pubmed/35905074 http://dx.doi.org/10.1371/journal.pntd.0010656 Text en © 2022 Chapagain et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Chapagain, Subash
Pal Singh, Prince
Le, Khanh
Safronetz, David
Wood, Heidi
Karniychuk, Uladzimir
Japanese encephalitis virus persists in the human reproductive epithelium and porcine reproductive tissues
title Japanese encephalitis virus persists in the human reproductive epithelium and porcine reproductive tissues
title_full Japanese encephalitis virus persists in the human reproductive epithelium and porcine reproductive tissues
title_fullStr Japanese encephalitis virus persists in the human reproductive epithelium and porcine reproductive tissues
title_full_unstemmed Japanese encephalitis virus persists in the human reproductive epithelium and porcine reproductive tissues
title_short Japanese encephalitis virus persists in the human reproductive epithelium and porcine reproductive tissues
title_sort japanese encephalitis virus persists in the human reproductive epithelium and porcine reproductive tissues
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9337681/
https://www.ncbi.nlm.nih.gov/pubmed/35905074
http://dx.doi.org/10.1371/journal.pntd.0010656
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