Gamma-herpesvirus latency requires T cell evasion during episome maintenance

Bennett, Neil J., May, Janet S. and Stevenson, Philip G. (2005) Gamma-herpesvirus latency requires T cell evasion during episome maintenance. PLoS Biology, 3 4: 0638-0649. doi:10.1371/journal.pbio.0030120


Author Bennett, Neil J.
May, Janet S.
Stevenson, Philip G.
Title Gamma-herpesvirus latency requires T cell evasion during episome maintenance
Journal name PLoS Biology   Check publisher's open access policy
ISSN 1544-9173
1545-7885
Publication date 2005-03-22
Sub-type Article (original research)
DOI 10.1371/journal.pbio.0030120
Open Access Status DOI
Volume 3
Issue 4
Start page 0638
End page 0649
Total pages 12
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Language eng
Formatted abstract
The gamma-herpesviruses persist as latent episomes in a dynamic lymphocyte pool. Their consequent need to express a viral episome maintenance protein presents a potential immune target. The glycine-alanine repeat of the Epstein-Barr virus episome maintenance protein, EBNA-1, limits EBNA-1 epitope presentation to CD8+ T lymphocytes (CTLs). However, CTL recognition occurs in vitro, so the significance of such evasion for viral fitness is unclear. We used the murine gamma-herpesvirus-68 (MHV-68) to define the in vivo contribution of cis-acting CTL evasion to host colonisation. Although the ORF73 episome maintenance protein of MHV-68 lacks a glycine-alanine repeat, it was equivalent to EBNA-1 in conferring limited presentation on linked epitopes. This was associated with reduced protein synthesis and reduced protein degradation. We bypassed the cis-acting evasion of ORF73 by using an internal ribosome entry site to express in trans-a CTL target from the same mRNA. This led to a severe, MHC class I-restricted and CTL-dependent reduction in viral latency. Thus, despite MHV-68 encoding at least two trans-acting CTL evasion proteins, cis-acting evasion during episome maintenance was essential for normal host colonisation.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Chemical Engineering Publications
 
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