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.

Project Start
Project End
Budget Start
Budget End
Support Year
27
Fiscal Year
2011
Total Cost
$290,988
Indirect Cost
City
State
Country
Zip Code
Sadaoka, Tomohiko; Schwartz, Cindi L; Rajbhandari, Labchan et al. (2018) Human Embryonic Stem Cell-Derived Neurons Are Highly Permissive for Varicella-Zoster Virus Lytic Infection. J Virol 92:
Cohen, Jeffrey I (2018) Herpesviruses in the Activated Phosphatidylinositol-3-Kinase-? Syndrome. Front Immunol 9:237
Kurapati, Sravya; Sadaoka, Tomohiko; Rajbhandari, Labchan et al. (2017) Role of the JNK Pathway in Varicella-Zoster Virus Lytic Infection and Reactivation. J Virol 91:
Sadaoka, Tomohiko; Depledge, Daniel P; Rajbhandari, Labchan et al. (2016) In vitro system using human neurons demonstrates that varicella-zoster vaccine virus is impaired for reactivation, but not latency. Proc Natl Acad Sci U S A 113:E2403-12
Gershon, Anne A; Breuer, Judith; Cohen, Jeffrey I et al. (2015) Varicella zoster virus infection. Nat Rev Dis Primers 1:15016
Cohen, Jeffrey I (2015) A new vaccine to prevent herpes zoster. N Engl J Med 372:2149-50
Bayat, Ahmad; Burbelo, Peter D; Browne, Sarah K et al. (2015) Anti-cytokine autoantibodies in postherpetic neuralgia. J Transl Med 13:333
Liu, XueQiao; Cohen, Jeffrey I (2015) The role of PI3K/Akt in human herpesvirus infection: From the bench to the bedside. Virology 479-480:568-77
Cohen, Jeffrey I; Ali, Mir A; Bayat, Ahmad et al. (2014) Detection of antibodies to varicella-zoster virus in recipients of the varicella vaccine by using a luciferase immunoprecipitation system assay. Clin Vaccine Immunol 21:1288-91
Yamamoto, Takenobu; Ali, Mir A; Liu, XueQiao et al. (2014) Activation of H2AX and ATM in varicella-zoster virus (VZV)-infected cells is associated with expression of specific VZV genes. Virology 452-453:52-8

Showing the most recent 10 out of 24 publications