CD8+ T cell evasion mandates CD4+ T cell control of chronic gamma-herpesvirus infection

Tan, Cindy S. E., Lawler, Clara and Stevenson, Philip G. (2017) CD8+ T cell evasion mandates CD4+ T cell control of chronic gamma-herpesvirus infection. PLoS Pathogens, 13 4: e1006311. doi:10.1371/journal.ppat.1006311


Author Tan, Cindy S. E.
Lawler, Clara
Stevenson, Philip G.
Title CD8+ T cell evasion mandates CD4+ T cell control of chronic gamma-herpesvirus infection
Formatted title
CD8+ T cell evasion mandates CD4+ T cell control of chronic gamma-herpesvirus infection
Journal name PLoS Pathogens   Check publisher's open access policy
ISSN 1553-7366
1553-7374
Publication date 2017-04-10
Sub-type Article (original research)
DOI 10.1371/journal.ppat.1006311
Open Access Status DOI
Volume 13
Issue 4
Start page e1006311
Total pages 17
Place of publication San Francisco, United States
Publisher Public Library of Science
Language eng
Subject 2405 Parasitology
2404 Microbiology
2403 Immunology
1312 Molecular Biology
1311 Genetics
2406 Virology
Abstract Gamma-herpesvirus infections are regulated by both CD4and CD8T cells. However clinical disease occurs mainly in CD4T cell-deficient hosts. In CD4T cell-deficient mice, CD8T cells control acute but not chronic lung infection by Murid Herpesvirus-4 (MuHV-4). We show that acute and chronic lung infections differ in distribution: most acute infection was epithelial, whereas most chronic infection was in myeloid cells. CD8T cells controlled epithelial infection, but CD4T cells and IFNγ were required to control myeloid cell infection. Disrupting the MuHV-4 K3, which degrades MHC class I heavy chains, increased viral epitope presentation by infected lung alveolar macrophages and allowed CD8T cells to prevent disease. Thus, viral CD8T cell evasion led to niche-specific immune control, and an essential role for CD4T cells in limiting chronic infection.
Formatted abstract
Gamma-herpesvirus infections are regulated by both CD4+ and CD8+ T cells. However clinical disease occurs mainly in CD4+ T cell-deficient hosts. In CD4+ T cell-deficient mice, CD8+ T cells control acute but not chronic lung infection by Murid Herpesvirus-4 (MuHV-4). We show that acute and chronic lung infections differ in distribution: most acute infection was epithelial, whereas most chronic infection was in myeloid cells. CD8+ T cells controlled epithelial infection, but CD4+ T cells and IFNγ were required to control myeloid cell infection. Disrupting the MuHV-4 K3, which degrades MHC class I heavy chains, increased viral epitope presentation by infected lung alveolar macrophages and allowed CD8+ T cells to prevent disease. Thus, viral CD8+ T cell evasion led to niche-specific immune control, and an essential role for CD4+ T cells in limiting chronic infection.
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 1060138
1064015
1079180
ft130100138
Institutional Status UQ
Additional Notes Article number e1006311

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
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School of Chemistry and Molecular Biosciences
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Created: Fri, 21 Apr 2017, 11:28:46 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences