Rag2 Deficiency Enhances Susceptibility to Systemic Mouse Adenovirus Type 1 Infection

Introduction: Recombination-activating gene 1 (Rag1) and Rag2, which are essential in V(D)J recombination, play a crucial role in B and T cell maturation. Method: We investigated the effects of Rag2 deficiency in clustered regularly interspaced short palindromic repeats/Cas9-mediated FVB-Rag2 knocko...

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Autores principales:	Han-Kyul Lee, Sun-Min Seo, Jun-Young Kim, Han-Woong Kim, Eui-Suk Jeong, Yang-Kyu Choi
Formato:	article
Lenguaje:	EN
Publicado:	Karger Publishers 2021
Materias:	Specialties of internal medicine RC581-951
Acceso en línea:	https://doaj.org/article/24c336e45690474090c0cfde561fb74c
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spelling	oai:doaj.org-article:24c336e45690474090c0cfde561fb74c2021-12-02T12:40:22ZRag2 Deficiency Enhances Susceptibility to Systemic Mouse Adenovirus Type 1 Infection0300-55261423-010010.1159/000520463https://doaj.org/article/24c336e45690474090c0cfde561fb74c2021-11-01T00:00:00Zhttps://www.karger.com/Article/FullText/520463https://doaj.org/toc/0300-5526https://doaj.org/toc/1423-0100Introduction: Recombination-activating gene 1 (Rag1) and Rag2, which are essential in V(D)J recombination, play a crucial role in B and T cell maturation. Method: We investigated the effects of Rag2 deficiency in clustered regularly interspaced short palindromic repeats/Cas9-mediated FVB-Rag2 knockout (KO) and wild-type (WT) mice infected with mouse adenovirus type 1 (MAV-1) via the intranasal route. Results: MAV-1 infection caused more severe histopathological changes in FVB-Rag2 KO mice than in WT mice. FVB-Rag2 KO mice exhibited moderate to severe inflammation on day 4 and severe inflammation on day 8 post infection. In contrast, WT mice showed mild inflammation on day 4 and mild to severe inflammation on day 8 post infection, including interstitial pneumonia and inflammatory cell infiltration in the lungs and liver. Viral loads in the spleen and kidneys were significantly higher in FVB-Rag2 KO mice than in WT mice on day 8 post infection. Levels of cytokines and chemokines, including MIP-1α, IP-10, IFN-α, IFN-γ, and TNF-α, were upregulated in the spleens of FVB-Rag2 KO mice compared with those of WT mice. The upregulation of several cytokines occurred concurrently with the histopathological changes. MAV-1 infection induced more severe systemic infection in FVB-Rag2 KO mice than in WT mice. Conclusion: In mice, Rag2 deficiency induces inflammatory cell recruitment via the upregulation of cytokine and chemokine levels. The MAV-1 infection model can be utilized to assess the efficacy and safety of therapeutic agents for human adenoviral diseases.Han-Kyul LeeSun-Min SeoJun-Young KimHan-Woong KimEui-Suk JeongYang-Kyu ChoiKarger PublishersarticleSpecialties of internal medicineRC581-951ENIntervirology (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Specialties of internal medicine RC581-951
spellingShingle	Specialties of internal medicine RC581-951 Han-Kyul Lee Sun-Min Seo Jun-Young Kim Han-Woong Kim Eui-Suk Jeong Yang-Kyu Choi Rag2 Deficiency Enhances Susceptibility to Systemic Mouse Adenovirus Type 1 Infection
description	Introduction: Recombination-activating gene 1 (Rag1) and Rag2, which are essential in V(D)J recombination, play a crucial role in B and T cell maturation. Method: We investigated the effects of Rag2 deficiency in clustered regularly interspaced short palindromic repeats/Cas9-mediated FVB-Rag2 knockout (KO) and wild-type (WT) mice infected with mouse adenovirus type 1 (MAV-1) via the intranasal route. Results: MAV-1 infection caused more severe histopathological changes in FVB-Rag2 KO mice than in WT mice. FVB-Rag2 KO mice exhibited moderate to severe inflammation on day 4 and severe inflammation on day 8 post infection. In contrast, WT mice showed mild inflammation on day 4 and mild to severe inflammation on day 8 post infection, including interstitial pneumonia and inflammatory cell infiltration in the lungs and liver. Viral loads in the spleen and kidneys were significantly higher in FVB-Rag2 KO mice than in WT mice on day 8 post infection. Levels of cytokines and chemokines, including MIP-1α, IP-10, IFN-α, IFN-γ, and TNF-α, were upregulated in the spleens of FVB-Rag2 KO mice compared with those of WT mice. The upregulation of several cytokines occurred concurrently with the histopathological changes. MAV-1 infection induced more severe systemic infection in FVB-Rag2 KO mice than in WT mice. Conclusion: In mice, Rag2 deficiency induces inflammatory cell recruitment via the upregulation of cytokine and chemokine levels. The MAV-1 infection model can be utilized to assess the efficacy and safety of therapeutic agents for human adenoviral diseases.
format	article
author	Han-Kyul Lee Sun-Min Seo Jun-Young Kim Han-Woong Kim Eui-Suk Jeong Yang-Kyu Choi
author_facet	Han-Kyul Lee Sun-Min Seo Jun-Young Kim Han-Woong Kim Eui-Suk Jeong Yang-Kyu Choi
author_sort	Han-Kyul Lee
title	Rag2 Deficiency Enhances Susceptibility to Systemic Mouse Adenovirus Type 1 Infection
title_short	Rag2 Deficiency Enhances Susceptibility to Systemic Mouse Adenovirus Type 1 Infection
title_full	Rag2 Deficiency Enhances Susceptibility to Systemic Mouse Adenovirus Type 1 Infection
title_fullStr	Rag2 Deficiency Enhances Susceptibility to Systemic Mouse Adenovirus Type 1 Infection
title_full_unstemmed	Rag2 Deficiency Enhances Susceptibility to Systemic Mouse Adenovirus Type 1 Infection
title_sort	rag2 deficiency enhances susceptibility to systemic mouse adenovirus type 1 infection
publisher	Karger Publishers
publishDate	2021
url	https://doaj.org/article/24c336e45690474090c0cfde561fb74c
work_keys_str_mv	AT hankyullee rag2deficiencyenhancessusceptibilitytosystemicmouseadenovirustype1infection AT sunminseo rag2deficiencyenhancessusceptibilitytosystemicmouseadenovirustype1infection AT junyoungkim rag2deficiencyenhancessusceptibilitytosystemicmouseadenovirustype1infection AT hanwoongkim rag2deficiencyenhancessusceptibilitytosystemicmouseadenovirustype1infection AT euisukjeong rag2deficiencyenhancessusceptibilitytosystemicmouseadenovirustype1infection AT yangkyuchoi rag2deficiencyenhancessusceptibilitytosystemicmouseadenovirustype1infection
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Rag2 Deficiency Enhances Susceptibility to Systemic Mouse Adenovirus Type 1 Infection

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