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. 2006 Apr 28;164(1):37–51. doi: 10.1111/j.1600-065X.1998.tb01206.x

Cytotoxic T‐lymphocyte escape viral variants: how important are they in viral evasion of immune clearance in vivo?

Persephone Borrow 1,✉, George M Shaw 2
PMCID: PMC7165923  PMID: 9795762

Abstract

Summary: Although viral variants which are not recognized by epitope‐specific cytotoxic T lymphocytes (CTL) have been shown lo arise during a number of persistent virus infections, in many cases their significance remains controversial: it has been argued that the immune response is sufficiently plastic to contain their replication. In this review, we describe the mechanisms by which amino acid changes in viral proteins may affect epitope recognition by virus‐specific CTL, and discuss the viral and immunological basis for the emergence of viral variants bearing such amino acid changes during infection. We then consider the impact that viral variation may have on the host CTL response and its ability to contain virus replication. We argue that the emergence of a viral variant demonstrates that it must have an in vivo replicative advantage, and that as such, the variant must tip the balance between virus replication and immune control somewhat in favor of the virus. Further, we suggest that although the immune response can evolve to recognize new viral epitopes, the CTL generated following such evolution frequently have a reduced ability to contain virus replication. We conclude that this escape mechanism likely does make a significant contribution to persistence/pathogenesis during a number of different virus infections.

Acknowledgements
The authors are supported by grant numbers R01 A137430‐03 (PB)and UO1 AI41530 (PB and GMS) from the NIH and by core funding from the Edward Jenner Institute for Vaccine Research (PB), This is publication number 5 from the Edward Jenner Institute for Vaccine Research.

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