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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
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.
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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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