Abstract

Varicella zoster virus (VZV) causes chickenpox and shingles. Virus infection of cells is known to trigger several signaling pathways that are important for cell proliferation and prevention of programmed cell death (also known as apoptosis). We have used a virus genome wide approach to identify functions of VZV proteins. Nearly all VZV genes were individually expressed in tissue culture cells along with a reporter system that responds to specific signaling proteins. Screening the VZV genome, we found that VZV ORF12 protein activated two protein kinases (ERK1/2 and p38). VZV deleted for ORF12 was impaired for activation of the kinases. ORF12 protein was shown to be located in the virus tegument (between the virus envelope and the nucleocapsid). We also found that ORF12 inhibits programmed cell death (apoptosis) induced by chemical treatment of the cells. These experiments indicate that ORF12 protein can activate signaling pathways and inhibit programmed cell death.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAI000430-28
Application #
8555759
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
28
Fiscal Year
2012
Total Cost
$224,339
Indirect Cost

  Institution

Name
National Institute of Allergy and Infectious Diseases
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

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
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
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
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

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