Role of PKR and Type I IFNs in viral control during primary and secondary infection.

Type I interferons (IFNs) are known to mediate viral control, and also promote survival and expansion of virus-specific CD8+ T cells. However, it is unclear whether signaling cascades involved in eliciting these diverse cellular effects are also distinct. One of the best-characterized anti-viral sig...

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Autores principales:	Yumi Nakayama, Erin H Plisch, Jeremy Sullivan, Chester Thomas, Charles J Czuprynski, Bryan R G Williams, M Suresh
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/67966041c01049d29b0c04ea45a7eb6e
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spelling	oai:doaj.org-article:67966041c01049d29b0c04ea45a7eb6e2021-12-02T20:00:33ZRole of PKR and Type I IFNs in viral control during primary and secondary infection.1553-73661553-737410.1371/journal.ppat.1000966https://doaj.org/article/67966041c01049d29b0c04ea45a7eb6e2010-06-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20585572/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Type I interferons (IFNs) are known to mediate viral control, and also promote survival and expansion of virus-specific CD8+ T cells. However, it is unclear whether signaling cascades involved in eliciting these diverse cellular effects are also distinct. One of the best-characterized anti-viral signaling mechanisms of Type I IFNs is mediated by the IFN-inducible dsRNA activated protein kinase, PKR. Here, we have investigated the role of PKR and Type I IFNs in regulating viral clearance and CD8+ T cell response during primary and secondary viral infections. Our studies demonstrate differential requirement for PKR, in viral control versus elicitation of CD8+ T cell responses during primary infection of mice with lymphocytic choriomeningitis virus (LCMV). PKR-deficient mice mounted potent CD8+ T cell responses, but failed to effectively control LCMV. The compromised LCMV control in the absence of PKR was multifactorial, and linked to less effective CD8+ T cell-mediated viral suppression, enhanced viral replication in cells, and lower steady state expression levels of IFN-responsive genes. Moreover, we show that despite normal expansion of memory CD8+ T cells and differentiation into effectors during a secondary response, effective clearance of LCMV but not vaccinia virus required PKR activity in infected cells. In the absence of Type I IFN signaling, secondary effector CD8+ T cells were ineffective in controlling both LCMV and vaccinia virus replication in vivo. These findings provide insight into cellular pathways of Type I IFN actions, and highlight the under-appreciated importance of innate immune mechanisms of viral control during secondary infections, despite the accelerated responses of memory CD8+ T cells. Additionally, the results presented here have furthered our understanding of the immune correlates of anti-viral protective immunity, which have implications in the rational design of vaccines.Yumi NakayamaErin H PlischJeremy SullivanChester ThomasCharles J CzuprynskiBryan R G WilliamsM SureshPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 6, Iss 6, p e1000966 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Yumi Nakayama Erin H Plisch Jeremy Sullivan Chester Thomas Charles J Czuprynski Bryan R G Williams M Suresh Role of PKR and Type I IFNs in viral control during primary and secondary infection.
description	Type I interferons (IFNs) are known to mediate viral control, and also promote survival and expansion of virus-specific CD8+ T cells. However, it is unclear whether signaling cascades involved in eliciting these diverse cellular effects are also distinct. One of the best-characterized anti-viral signaling mechanisms of Type I IFNs is mediated by the IFN-inducible dsRNA activated protein kinase, PKR. Here, we have investigated the role of PKR and Type I IFNs in regulating viral clearance and CD8+ T cell response during primary and secondary viral infections. Our studies demonstrate differential requirement for PKR, in viral control versus elicitation of CD8+ T cell responses during primary infection of mice with lymphocytic choriomeningitis virus (LCMV). PKR-deficient mice mounted potent CD8+ T cell responses, but failed to effectively control LCMV. The compromised LCMV control in the absence of PKR was multifactorial, and linked to less effective CD8+ T cell-mediated viral suppression, enhanced viral replication in cells, and lower steady state expression levels of IFN-responsive genes. Moreover, we show that despite normal expansion of memory CD8+ T cells and differentiation into effectors during a secondary response, effective clearance of LCMV but not vaccinia virus required PKR activity in infected cells. In the absence of Type I IFN signaling, secondary effector CD8+ T cells were ineffective in controlling both LCMV and vaccinia virus replication in vivo. These findings provide insight into cellular pathways of Type I IFN actions, and highlight the under-appreciated importance of innate immune mechanisms of viral control during secondary infections, despite the accelerated responses of memory CD8+ T cells. Additionally, the results presented here have furthered our understanding of the immune correlates of anti-viral protective immunity, which have implications in the rational design of vaccines.
format	article
author	Yumi Nakayama Erin H Plisch Jeremy Sullivan Chester Thomas Charles J Czuprynski Bryan R G Williams M Suresh
author_facet	Yumi Nakayama Erin H Plisch Jeremy Sullivan Chester Thomas Charles J Czuprynski Bryan R G Williams M Suresh
author_sort	Yumi Nakayama
title	Role of PKR and Type I IFNs in viral control during primary and secondary infection.
title_short	Role of PKR and Type I IFNs in viral control during primary and secondary infection.
title_full	Role of PKR and Type I IFNs in viral control during primary and secondary infection.
title_fullStr	Role of PKR and Type I IFNs in viral control during primary and secondary infection.
title_full_unstemmed	Role of PKR and Type I IFNs in viral control during primary and secondary infection.
title_sort	role of pkr and type i ifns in viral control during primary and secondary infection.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/67966041c01049d29b0c04ea45a7eb6e
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Role of PKR and Type I IFNs in viral control during primary and secondary infection.

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