| pubmed-article:20585572 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:20585572 | lifeskim:mentions | umls-concept:C0521026 | lld:lifeskim |
| pubmed-article:20585572 | lifeskim:mentions | umls-concept:C0035820 | lld:lifeskim |
| pubmed-article:20585572 | lifeskim:mentions | umls-concept:C0332307 | lld:lifeskim |
| pubmed-article:20585572 | lifeskim:mentions | umls-concept:C0021747 | lld:lifeskim |
| pubmed-article:20585572 | lifeskim:mentions | umls-concept:C0058980 | lld:lifeskim |
| pubmed-article:20585572 | lifeskim:mentions | umls-concept:C0442886 | lld:lifeskim |
| pubmed-article:20585572 | lifeskim:mentions | umls-concept:C1539341 | lld:lifeskim |
| pubmed-article:20585572 | lifeskim:mentions | umls-concept:C1415900 | lld:lifeskim |
| pubmed-article:20585572 | lifeskim:mentions | umls-concept:C2587213 | lld:lifeskim |
| pubmed-article:20585572 | lifeskim:mentions | umls-concept:C0205225 | lld:lifeskim |
| pubmed-article:20585572 | pubmed:issue | 6 | lld:pubmed |
| pubmed-article:20585572 | pubmed:dateCreated | 2010-6-29 | lld:pubmed |
| pubmed-article:20585572 | pubmed:abstractText | 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. | lld:pubmed |
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| pubmed-article:20585572 | pubmed:language | eng | lld:pubmed |
| pubmed-article:20585572 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20585572 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:20585572 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:20585572 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:20585572 | pubmed:issn | 1553-7374 | lld:pubmed |
| pubmed-article:20585572 | pubmed:author | pubmed-author:SureshMM | lld:pubmed |
| pubmed-article:20585572 | pubmed:author | pubmed-author:WilliamsBryan... | lld:pubmed |
| pubmed-article:20585572 | pubmed:author | pubmed-author:CzuprynskiCha... | lld:pubmed |
| pubmed-article:20585572 | pubmed:author | pubmed-author:NakayamaYumiY | lld:pubmed |
| pubmed-article:20585572 | pubmed:author | pubmed-author:ChesterThomas... | lld:pubmed |
| pubmed-article:20585572 | pubmed:author | pubmed-author:PlischErin... | lld:pubmed |
| pubmed-article:20585572 | pubmed:author | pubmed-author:SullivanJerem... | lld:pubmed |
| pubmed-article:20585572 | pubmed:issnType | Electronic | lld:pubmed |
