The ?134.5 protein, present both in herpes simplex virus 1 and 2 (HSV), plays an essential role in viral virulence. Unlike wild-type virus, HSV mutants that lack the ?134.5 gene are incapable of replicating and causing diseases. However, the underlying mechanisms are not incompletely understood. The major goal of the proposed research is to investigate the biological functions of ?134.5 during HSV infection. HSV ?134.5 contains an amino-terminal domain, a linker region of triplet repeats, and a carboxyl- terminal domain. A critical function of ?134.5 is to block the interferon response mediated by double-stranded RNA dependent protein kinase PKR. In addition, ?134.5 is involved in virus egress. This activity maps to the amino-terminus of ?134.5 that shuttles between the nucleus, nucleolus and cytoplasm. It is thought that coordinated actions of functional elements in the ?134.5 protein and cellular factors facilitate virus egress that contributes to viral virulence. To test this hypothesis, mutational analysis will be performed to define functional modules of ?134.5. Recombinant viruses will be constructed to study viral replication, spread, and the interferon response in infected cells. Experiments will also be performed to identify targets of ?134.5. Furthermore, studies will be carried out to explore the molecular nature by which ?134.5 promotes viral infection. Taken together, these studies will provide insights into the mechanisms of HSV pathogenesis.

Public Health Relevance

In summary, herpes simplex viruses are human pathogens that cause diseases such as genital herpes, keratitis, and encephalitis. This research is designed to investigate how a pathogenic factor of herpes simplex viruses facilitates viral infection, which may lead to the development of novel vaccines and antiviral therapeutics.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
3R21AI081711-01S1
Application #
7878400
Study Section
Special Emphasis Panel (ZRG1-IDM-P (91))
Program Officer
Beisel, Christopher E
Project Start
2009-08-11
Project End
2011-08-31
Budget Start
2009-08-11
Budget End
2011-08-31
Support Year
1
Fiscal Year
2009
Total Cost
$18,560
Indirect Cost
Name
University of Illinois at Chicago
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
098987217
City
Chicago
State
IL
Country
United States
Zip Code
60612