Primary infection with varicella-zoster virus (VZV) causes chickenpox, and reactivation of the virus from latency results in zoster. The purpose of this project is to study the mechanisms for immune evasion and latent infection by VZV. We have shown that infection of fibroblasts with VZV results in down-regulation of expression of proteins that are important for recognition by the immune system (MHC class I antigens). While the total amount of these proteins was unchanged in infected cells, the amount of class I antigen expressed on the surface of infected cells was reduced. Since MHC class I proteins are important for the immune system to recognize VZV infected cells, the ability of the virus to reduce their expression provides a mechanism by which the virus might evade the immune system. We have also studied a VZV gene (ORF21) that has been reported to be expressed during latency in humans. During infection of cells in culture, this gene was shown to be up-regulated by VZV infection or by expression of a VZV immediate-early gene (ORF62). The ends of the RNA transcripts that encode VZV ORF21 have been mapped and the region of the gene that regulates its expression (promoter) has been identified.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000430-14
Application #
6098935
Study Section
Special Emphasis Panel (LCI)
Project Start
Project End
Budget Start
Budget End
Support Year
14
Fiscal Year
1998
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
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
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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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