Document Detail

Activation of NF-κB in CD8+ dendritic cells Ex Vivo by the γ134.5 null mutant correlates with immunity against herpes simplex virus 1.
MedLine Citation:
PMID:  22072757     Owner:  NLM     Status:  MEDLINE    
The γ(1)34.5 protein of herpes simplex viruses (HSV) is essential for virulence. Accordingly, an HSV mutant lacking γ(1)34.5 is attenuated in vivo. Despite its vaccine potential, the mechanism by which the γ(1)34.5 null mutant triggers protective immunity is unknown. In this report we show that vaccination with the γ(1)34.5 null mutant protects against lethal challenge from wild-type virus via IκB kinase in dendritic cells (DCs), which sense virus-associated molecular patterns. Unlike mock-treated DCs, DCs primed with the γ(1)34.5 null mutant ex vivo mediate resistance to wild-type HSV after adoptive transfer into naïve mice. Furthermore, the γ(1)34.5 null mutant activates IκB kinase, which facilitates p65/RelA phosphorylation and nuclear translocation, resulting in DC maturation. While unable to produce infectious virus in DCs, this mutant virus expresses early and late genes. In its abortive infection, the γ(1)34.5 null mutant induces protective immunity more effectively in CD8(+) DCs than in CD8(-) DCs. This is mirrored by a higher level of interleukin-6 (IL-6) and IL-12 secretion by CD8(+) DCs than CD8(-) DCs. Remarkably, inhibition of p65/RelA phosphorylation or nuclear translocation in CD8(+) DCs disrupts protective immunity. These results suggest that engagement of the γ(1)34.5 null mutant with CD8(+) DCs elicits innate immunity to activate NF-κB, which translates into protective immunity.
Huali Jin; Yijie Ma; Zhipeng Yan; Bellur S Prabhakar; Bin He
Related Documents :
17470337 - Role of inflammation in the progression of heart failure.
10984127 - Differential effect of benzydamine on pro- versus anti-inflammatory cytokine production...
19053207 - Emerging applications of anticytokine vaccines.
19803417 - Proinflammatory cytokines in crp baseline regulation.
16611237 - Modulation of alp4 function in schizosaccharomyces pombe induces novel phenotypes that ...
21436367 - Aeromonas spp. induces apoptosis of epithelial cells through an oxidant dependent activ...
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-11-09
Journal Detail:
Title:  Journal of virology     Volume:  86     ISSN:  1098-5514     ISO Abbreviation:  J. Virol.     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2011-12-29     Completed Date:  2012-02-22     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1059-68     Citation Subset:  IM    
Department of Microbiology and Immunology, College of Medicine, University of Illinois, Chicago, Illinois, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Antigens, CD8 / genetics,  immunology
Cells, Cultured
Dendritic Cells / immunology*,  virology
Herpes Simplex / genetics,  immunology*,  virology
Herpesvirus 1, Human / immunology*
Mice, Inbred BALB C
NF-kappa B / genetics,  immunology*
Sequence Deletion*
Viral Proteins / genetics*,  immunology
Grant Support
Reg. No./Substance:
0/Antigens, CD8; 0/NF-kappa B; 0/Viral Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Chicken cells sense influenza A virus infection through MDA5 and CARDIF signaling involving LGP2.
Next Document:  Potent autologous and heterologous neutralizing antibody responses occur in HIV-2 infection across a...