Herpesviruses encode a number of genes that encode proteins that limit the host response to the virus, allowing the virus to avoid destruction by the immune system. Certain herpesvirus proteins block recognition of virus-infected cells by down-regulating expression of MHC class I molecules on the surface of infected cells. One mechanism that viruses accomplish this is by inhibiting transport of viral proteins by the host cell proteins TAP (transporter associated with antigen processing). In collaboration with Emmanuel Wiertz at the University Medical Center of Utrecht in the Netherlands, we found that a herpesvirus protein that inhibits TAP, UL49.5 protein, is present in a large number of herpesviruses in the genus varicellovirus. These include herpesviruses in cattle, pigs, horses, cats, deer, and other animals. While varicella-zoster virus (VZV) is also a member of the genus varicellovirus, and we previously showed that VZV down-regulates MHC class I on the surface of infected cells, we found that the UL49.5 protein of VZV did not inhibit TAP function. This suggests that VZV UL49.5 has either lost this activity, or that the virus is still evolving and may ultimately develop this function.
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