( h the murine gamma-herpesvirus-68 (MHV-...)Touching Molecules With Your Bare Hands

h the murine gamma-herpesvirus-68 (MHV-68). Though MHV-68 infects mice, it behaves similarly to EBV and KSHV infections in humans, producing an acute mononucleosis-like illness and a pervasive pool of latently infected B cells. The episome maintenance protein in MHV-68 and KSHV is called ORF73. None of the viruses can maintain latent infections with deficient episome maintenance proteins.

Stevenson and colleagues first demonstrated that ORF73 limits T cell recognition and then identified a key region responsible for immune evasion by modifying different regions of the viral protein. In the next round of experiments, the authors asked how the viral protein manages this feat. They discovered that ORF73 limits T cell recognition much like EBNA-1 does, by reducing synthesis and degradation of the protein. One region strongly associated with inhibiting epitope presentation to killer T cells corresponded to reduced protein synthesis. When the authors modified the ORF73 transcript to circumvent T cell evasion, the T cells “wiped out?latent virus. These results indicate that avoiding epitope presentation during episome maintenance is key to the virus’s survival.

Interestingly, the MHV-68 episome maintenance protein mediates immune evasion even though it lacks the amino acid element that does the job for EBV. Future studies will have to determine the responsible MHV-68 epitope and the mechanisms that engineer immune avoidance. Since a majority of epitopes that killer T cells recognize come from aborted translation events, it may be that evasive action is taken at the RNA transcript stage, before RNA is translated into protein. Evading killer T cells, the authors argue, is key to the survival of the gamma-herpesvirus. By figuring out just how evasion occurs, scientists can identify a promising target for controlling infection.

Copyright: © 2005 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons
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