Abstract

Human herpes viruses are responsible for a variety of clinically significant diseases which, under certain circumstances, can be life threatening. Because viral DNA synthesis is central to the HSV replication process, identification and characterization of viral DNA synthetic enzymes and DNA structural elements required for initiation of DNA synthesis are essential prerequisites in efforts aimed at controlling HSV infection. Preliminary evidence has suggested the existence of a """"""""viral DNA replication complex"""""""" composed of several virus-coded enzymes. The genetic studies proposed herein are designed to identify viral genes involved in HSV-1 DNA synthesis through the isolation and characterization of a series of isogenic temperature-sensitive (ts) mutants of HSV-1, 2) provide further genetic evidence for the existence of a viral DNA replication complex and identify its components through the isolation and mapping of ts+ extragenic suppressor mutations, and 3) localize and characterize the putative origin of replication located in the long unique region of the HSV-1 genome (ori(L)). It is anticipated that the availability of HSV-1 ts mutants in essential viral replication genes will not only serve to further our understanding of HSV DNA synthesis but will also identify viral enzymes as potential targets of antiviral chemotherapy.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI021747-02
Application #
3132049
Study Section
Experimental Virology Study Section (EVR)
Project Start
1984-12-01
Project End
1987-11-30
Budget Start
1985-12-01
Budget End
1986-11-30
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
University of Connecticut
Department
Type
School of Medicine & Dentistry
DUNS #
City
Farmington
State
CT
Country
United States
Zip Code
06030

  Publications

Grady, Lorry M; Szczepaniak, Renata; Murelli, Ryan P et al. (2017) The exonuclease activity of HSV-1 UL12 is required for the production of viral DNA that can be packaged to produce infectious virus. J Virol :
Bermek, Oya; Weller, Sandra K; Griffith, Jack D (2017) The UL8 subunit of the helicase-primase complex of herpes simplex virus promotes DNA annealing and has a high affinity for replication forks. J Biol Chem 292:15611-15621
Darwish, Anthar S; Grady, Lorry M; Bai, Ping et al. (2016) ICP8 Filament Formation Is Essential for Replication Compartment Formation during Herpes Simplex Virus Infection. J Virol 90:2561-70
Lou, Dianne I; Kim, Eui Tae; Meyerson, Nicholas R et al. (2016) An Intrinsically Disordered Region of the DNA Repair Protein Nbs1 Is a Species-Specific Barrier to Herpes Simplex Virus 1 in Primates. Cell Host Microbe 20:178-88
Smith, Samantha; Weller, Sandra K (2015) HSV-I and the cellular DNA damage response. Future Virol 10:383-397
Mossman, Karen L; Weller, Sandra K (2015) HSV cheats the executioner. Cell Host Microbe 17:148-51
Pozhidaeva, Alexandra K; Mohni, Kareem N; Dhe-Paganon, Sirano et al. (2015) Structural Characterization of Interaction between Human Ubiquitin-specific Protease 7 and Immediate-Early Protein ICP0 of Herpes Simplex Virus-1. J Biol Chem 290:22907-18
Smith, Samantha; Reuven, Nina; Mohni, Kareem N et al. (2014) Structure of the herpes simplex virus 1 genome: manipulation of nicks and gaps can abrogate infectivity and alter the cellular DNA damage response. J Virol 88:10146-56
Weller, Sandra K; Sawitzke, James A (2014) Recombination promoted by DNA viruses: phage ? to herpes simplex virus. Annu Rev Microbiol 68:237-58
Grady, Lorry M; Bai, Ping; Weller, Sandra K (2014) HSV-1 protein expression using recombinant baculoviruses. Methods Mol Biol 1144:293-304

Showing the most recent 10 out of 59 publications