Abstract

The major basic research focus of this laboratory involves this project, with the following goals: 1) to identify, map and characterize varicella-zoster virus genes and proteins active in latent or productive infections. 2) to define the temporal sequence of gene expression. 3) to determine the interaction of antiviral drugs with viral gene products through a molecular analysis of drug-resistant mutants. 4) to characterize the molecular epidemiology of varicella-zoster virus infections. To accomplish these ends we have constructed recombinant libraries of the complete VZV genome in a variety of vectors. The genome and most, if not all, of the major viral messages have been identified and preliminarily mapped, and two gene products representing immediate early and early functions have been identified and located. Our current efforts are directed at finer mapping of selected viral transcripts, defining the temporal sequence of gene expression using cell-free virus, and utilizing herpes simplex virus mutants to help identify and map complementary VZV gene functions in the establishment of an in situ hybridization system using a 35S riboprobe for detection of latent sequences within human trigeminal ganglia.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000430-02
Application #
3960607
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
Niaid Extramural Activities
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Rau, Rachel; Fitzhugh, Courtney D; Baird, Kristin et al. (2008) Triad of severe abdominal pain, inappropriate antidiuretic hormone secretion, and disseminated varicella-zoster virus infection preceding cutaneous manifestations after hematopoietic stem cell transplantation: utility of PCR for early recognition and ther Pediatr Infect Dis J 27:265-8
Cohen, Jeffrey I; Krogmann, Tammy; Pesnicak, Lesley et al. (2007) Absence or overexpression of the Varicella-Zoster Virus (VZV) ORF29 latency-associated protein impairs late gene expression and reduces VZV latency in a rodent model. J Virol 81:1586-91
Li, Qingxue; Krogmann, Tammy; Ali, Mir A et al. (2007) The amino terminus of varicella-zoster virus (VZV) glycoprotein E is required for binding to insulin-degrading enzyme, a VZV receptor. J Virol 81:8525-32
Cohen, Jeffrey I (2007) Varicella-zoster vaccine virus: evolution in action. Proc Natl Acad Sci U S A 104:7-8
Ambagala, Aruna P N; Cohen, Jeffrey I (2007) Varicella-Zoster virus IE63, a major viral latency protein, is required to inhibit the alpha interferon-induced antiviral response. J Virol 81:7844-51
Hoover, Susan E; Cohrs, Randall J; Rangel, Zoila G et al. (2006) Downregulation of varicella-zoster virus (VZV) immediate-early ORF62 transcription by VZV ORF63 correlates with virus replication in vitro and with latency. J Virol 80:3459-68
Cohrs, Randall J; Gilden, Donald H; Gomi, Yasuyuki et al. (2006) Comparison of virus transcription during lytic infection of the Oka parental and vaccine strains of Varicella-Zoster virus. J Virol 80:2076-82
Li, Qingxue; Ali, Mir A; Cohen, Jeffrey I (2006) Insulin degrading enzyme is a cellular receptor mediating varicella-zoster virus infection and cell-to-cell spread. Cell 127:305-16
Hu, Huiling; Cohen, Jeffrey I (2005) Varicella-zoster virus open reading frame 47 (ORF47) protein is critical for virus replication in dendritic cells and for spread to other cells. Virology 337:304-11
Cohen, Jeffrey I; Krogmann, Tammy; Bontems, Sebastien et al. (2005) Regions of the varicella-zoster virus open reading frame 63 latency-associated protein important for replication in vitro are also critical for efficient establishment of latency. J Virol 79:5069-77

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