RIG-I and MDA5 Protect Mice From Pichinde Virus Infection by Controlling Viral Replication and Regulating Immune Responses to the Infection

RIG-I and MDA5 are major cytoplasmic innate-immune sensor proteins that recognize aberrant double-stranded RNAs generated during virus infection to activate type 1 interferon (IFN-I) and IFN-stimulated gene (ISG) expressions to control virus infection. The roles of RIG-I and MDA5 in controlling repl...

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Autores principales:	Morgan Brisse, Qinfeng Huang, Mizanur Rahman, Da Di, Yuying Liang, Hinh Ly
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	Pichinde virus mammarenavirus arenavirus innate immunity RIG-I MDA5 Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/c1563cafbac644feb7d2e5c31997264f
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spelling	oai:doaj.org-article:c1563cafbac644feb7d2e5c31997264f2021-12-03T04:58:19ZRIG-I and MDA5 Protect Mice From Pichinde Virus Infection by Controlling Viral Replication and Regulating Immune Responses to the Infection1664-322410.3389/fimmu.2021.801811https://doaj.org/article/c1563cafbac644feb7d2e5c31997264f2021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.801811/fullhttps://doaj.org/toc/1664-3224RIG-I and MDA5 are major cytoplasmic innate-immune sensor proteins that recognize aberrant double-stranded RNAs generated during virus infection to activate type 1 interferon (IFN-I) and IFN-stimulated gene (ISG) expressions to control virus infection. The roles of RIG-I and MDA5 in controlling replication of Pichinde virus (PICV), a mammarenavirus, in mice have not been examined. Here, we showed that MDA5 single knockout (SKO) and RIG-I/MDA5 double knockout (DKO) mice are highly susceptible to PICV infection as evidenced by their significant reduction in body weights during the course of the infection, validating the important roles of these innate-immune sensor proteins in controlling PICV infection. Compared to the wildtype mice, SKO and DKO mice infected with PICV had significantly higher virus titers and lower IFN-I expressions early in the infection but appeared to exhibit a late and heightened level of adaptive immune responses to clear the infection. When a recombinant rPICV mutant virus (rPICV-NPmut) that lacks the ability to suppress IFN-I was used to infect mice, as expected, there were heightened levels of IFN-I and ISG expressions in the wild-type mice, whereas infected SKO and DKO mice showed delayed mouse growth kinetics and relatively low, delayed, and transient levels of innate and adaptive immune responses to this viral infection. Taken together, our data suggest that PICV infection triggers activation of immune sensors that include but might not be necessarily limited to RIG-I and MDA5 to stimulate effective innate and adaptive immune responses to control virus infection in mice.Morgan BrisseMorgan BrisseQinfeng HuangMizanur RahmanDa DiYuying LiangHinh LyHinh LyFrontiers Media S.A.articlePichinde virusmammarenavirusarenavirusinnate immunityRIG-IMDA5Immunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Pichinde virus mammarenavirus arenavirus innate immunity RIG-I MDA5 Immunologic diseases. Allergy RC581-607
spellingShingle	Pichinde virus mammarenavirus arenavirus innate immunity RIG-I MDA5 Immunologic diseases. Allergy RC581-607 Morgan Brisse Morgan Brisse Qinfeng Huang Mizanur Rahman Da Di Yuying Liang Hinh Ly Hinh Ly RIG-I and MDA5 Protect Mice From Pichinde Virus Infection by Controlling Viral Replication and Regulating Immune Responses to the Infection
description	RIG-I and MDA5 are major cytoplasmic innate-immune sensor proteins that recognize aberrant double-stranded RNAs generated during virus infection to activate type 1 interferon (IFN-I) and IFN-stimulated gene (ISG) expressions to control virus infection. The roles of RIG-I and MDA5 in controlling replication of Pichinde virus (PICV), a mammarenavirus, in mice have not been examined. Here, we showed that MDA5 single knockout (SKO) and RIG-I/MDA5 double knockout (DKO) mice are highly susceptible to PICV infection as evidenced by their significant reduction in body weights during the course of the infection, validating the important roles of these innate-immune sensor proteins in controlling PICV infection. Compared to the wildtype mice, SKO and DKO mice infected with PICV had significantly higher virus titers and lower IFN-I expressions early in the infection but appeared to exhibit a late and heightened level of adaptive immune responses to clear the infection. When a recombinant rPICV mutant virus (rPICV-NPmut) that lacks the ability to suppress IFN-I was used to infect mice, as expected, there were heightened levels of IFN-I and ISG expressions in the wild-type mice, whereas infected SKO and DKO mice showed delayed mouse growth kinetics and relatively low, delayed, and transient levels of innate and adaptive immune responses to this viral infection. Taken together, our data suggest that PICV infection triggers activation of immune sensors that include but might not be necessarily limited to RIG-I and MDA5 to stimulate effective innate and adaptive immune responses to control virus infection in mice.
format	article
author	Morgan Brisse Morgan Brisse Qinfeng Huang Mizanur Rahman Da Di Yuying Liang Hinh Ly Hinh Ly
author_facet	Morgan Brisse Morgan Brisse Qinfeng Huang Mizanur Rahman Da Di Yuying Liang Hinh Ly Hinh Ly
author_sort	Morgan Brisse
title	RIG-I and MDA5 Protect Mice From Pichinde Virus Infection by Controlling Viral Replication and Regulating Immune Responses to the Infection
title_short	RIG-I and MDA5 Protect Mice From Pichinde Virus Infection by Controlling Viral Replication and Regulating Immune Responses to the Infection
title_full	RIG-I and MDA5 Protect Mice From Pichinde Virus Infection by Controlling Viral Replication and Regulating Immune Responses to the Infection
title_fullStr	RIG-I and MDA5 Protect Mice From Pichinde Virus Infection by Controlling Viral Replication and Regulating Immune Responses to the Infection
title_full_unstemmed	RIG-I and MDA5 Protect Mice From Pichinde Virus Infection by Controlling Viral Replication and Regulating Immune Responses to the Infection
title_sort	rig-i and mda5 protect mice from pichinde virus infection by controlling viral replication and regulating immune responses to the infection
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/c1563cafbac644feb7d2e5c31997264f
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RIG-I and MDA5 Protect Mice From Pichinde Virus Infection by Controlling Viral Replication and Regulating Immune Responses to the Infection

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