Gamma-Herpesvirus Latency Requires T Cell Evasion during Episome Maintenance
<p>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 e...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2005-01-01
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| Series: | PLoS Biology |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1371/journal.pbio.0030120 |
| Summary: | <p>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<sup>+</sup> 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 <italic>cis</italic>-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 <italic>cis-</italic>acting evasion of ORF73 by using an internal ribosome entry site to express in <italic>trans</italic>-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 <italic>trans</italic>-acting CTL evasion proteins, <italic>cis-</italic>acting evasion during episome maintenance was essential for normal host colonisation.</p> |
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| ISSN: | 1544-9173 1545-7885 |