Endogenous Retroviruses Provide Protection Against Vaginal HSV-2 Disease
Endogenous retroviruses (ERVs) are genomic sequences that originated from retroviruses and are present in most eukaryotic genomes. Both beneficial and detrimental functions are attributed to ERVs, but whether ERVs contribute to antiviral immunity is not well understood. Here, we used herpes simplex...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8764156/ https://www.ncbi.nlm.nih.gov/pubmed/35058919 http://dx.doi.org/10.3389/fimmu.2021.758721 |
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author | Jayewickreme, Radeesha Mao, Tianyang Philbrick, William Kong, Yong Treger, Rebecca S. Lu, Peiwen Rakib, Tasfia Dong, Huiping Dang-Lawson, May Guild, W. Austin Lau, Tatiana J. Iwasaki, Akiko Tokuyama, Maria |
author_facet | Jayewickreme, Radeesha Mao, Tianyang Philbrick, William Kong, Yong Treger, Rebecca S. Lu, Peiwen Rakib, Tasfia Dong, Huiping Dang-Lawson, May Guild, W. Austin Lau, Tatiana J. Iwasaki, Akiko Tokuyama, Maria |
author_sort | Jayewickreme, Radeesha |
collection | PubMed |
description | Endogenous retroviruses (ERVs) are genomic sequences that originated from retroviruses and are present in most eukaryotic genomes. Both beneficial and detrimental functions are attributed to ERVs, but whether ERVs contribute to antiviral immunity is not well understood. Here, we used herpes simplex virus type 2 (HSV-2) infection as a model and found that Toll-like receptor 7 (Tlr7 (-/-)) deficient mice that have high systemic levels of infectious ERVs are protected from intravaginal HSV-2 infection and disease, compared to wildtype C57BL/6 mice. We deleted the endogenous ecotropic murine leukemia virus (Emv2) locus on the Tlr7 (-/-) background (Emv2 (-/-) Tlr7 (-/-)) and found that Emv2 (-/-) Tlr7 (-/-) mice lose protection against HSV-2 infection. Intravaginal application of purified ERVs from Tlr7(-/-) mice prior to HSV-2 infection delays disease in both wildtype and highly susceptible interferon-alpha receptor-deficient (Ifnar1(-) (/-)) mice. However, intravaginal ERV treatment did not protect Emv2(-/-)Tlr7(-/-) mice from HSV-2 disease, suggesting that the protective mechanism mediated by exogenous ERV treatment may differ from that of constitutively and systemically expressed ERVs in Tlr7(-/-) mice. We did not observe enhanced type I interferon (IFN-I) signaling in the vaginal tissues from Tlr7-/- mice, and instead found enrichment in genes associated with extracellular matrix organization. Together, our results revealed that constitutive and/or systemic expression of ERVs protect mice against vaginal HSV-2 infection and delay disease. |
format | Online Article Text |
id | pubmed-8764156 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-87641562022-01-19 Endogenous Retroviruses Provide Protection Against Vaginal HSV-2 Disease Jayewickreme, Radeesha Mao, Tianyang Philbrick, William Kong, Yong Treger, Rebecca S. Lu, Peiwen Rakib, Tasfia Dong, Huiping Dang-Lawson, May Guild, W. Austin Lau, Tatiana J. Iwasaki, Akiko Tokuyama, Maria Front Immunol Immunology Endogenous retroviruses (ERVs) are genomic sequences that originated from retroviruses and are present in most eukaryotic genomes. Both beneficial and detrimental functions are attributed to ERVs, but whether ERVs contribute to antiviral immunity is not well understood. Here, we used herpes simplex virus type 2 (HSV-2) infection as a model and found that Toll-like receptor 7 (Tlr7 (-/-)) deficient mice that have high systemic levels of infectious ERVs are protected from intravaginal HSV-2 infection and disease, compared to wildtype C57BL/6 mice. We deleted the endogenous ecotropic murine leukemia virus (Emv2) locus on the Tlr7 (-/-) background (Emv2 (-/-) Tlr7 (-/-)) and found that Emv2 (-/-) Tlr7 (-/-) mice lose protection against HSV-2 infection. Intravaginal application of purified ERVs from Tlr7(-/-) mice prior to HSV-2 infection delays disease in both wildtype and highly susceptible interferon-alpha receptor-deficient (Ifnar1(-) (/-)) mice. However, intravaginal ERV treatment did not protect Emv2(-/-)Tlr7(-/-) mice from HSV-2 disease, suggesting that the protective mechanism mediated by exogenous ERV treatment may differ from that of constitutively and systemically expressed ERVs in Tlr7(-/-) mice. We did not observe enhanced type I interferon (IFN-I) signaling in the vaginal tissues from Tlr7-/- mice, and instead found enrichment in genes associated with extracellular matrix organization. Together, our results revealed that constitutive and/or systemic expression of ERVs protect mice against vaginal HSV-2 infection and delay disease. Frontiers Media S.A. 2022-01-04 /pmc/articles/PMC8764156/ /pubmed/35058919 http://dx.doi.org/10.3389/fimmu.2021.758721 Text en Copyright © 2022 Jayewickreme, Mao, Philbrick, Kong, Treger, Lu, Rakib, Dong, Dang-Lawson, Guild, Lau, Iwasaki and Tokuyama https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Jayewickreme, Radeesha Mao, Tianyang Philbrick, William Kong, Yong Treger, Rebecca S. Lu, Peiwen Rakib, Tasfia Dong, Huiping Dang-Lawson, May Guild, W. Austin Lau, Tatiana J. Iwasaki, Akiko Tokuyama, Maria Endogenous Retroviruses Provide Protection Against Vaginal HSV-2 Disease |
title | Endogenous Retroviruses Provide Protection Against Vaginal HSV-2 Disease |
title_full | Endogenous Retroviruses Provide Protection Against Vaginal HSV-2 Disease |
title_fullStr | Endogenous Retroviruses Provide Protection Against Vaginal HSV-2 Disease |
title_full_unstemmed | Endogenous Retroviruses Provide Protection Against Vaginal HSV-2 Disease |
title_short | Endogenous Retroviruses Provide Protection Against Vaginal HSV-2 Disease |
title_sort | endogenous retroviruses provide protection against vaginal hsv-2 disease |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8764156/ https://www.ncbi.nlm.nih.gov/pubmed/35058919 http://dx.doi.org/10.3389/fimmu.2021.758721 |
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