Molecular Biology of Varicella-Zoster Virus Infections

Cohen, J I.

Abstract

Primary infection with varicella-zoster virus (VZV) causes chickenpox, and reactivation of the virus from latency results in zoster. The goals of this project are to identify and determine the function of VZV genes that are expressed during active infection and during latency in the body. VZV genes that are expressed during active infection and regulate viral gene expression in vitro are being studied. Analysis of VZV gene products during acute infection indicate that at least four VZV genes, ORF4, ORF10, ORF61, and ORF62 transactivate the expression of other VZV genes in vitro, and two of these genes (ORF10, ORF62) activate transcription directly. Thus, a limited number of VZV gene products are critical during acute viral infection in regulating VZV replication. Three of these VZV genes (ORF10, ORF61, and ORF62) can complement the function of their herpes simplex virus homologs. Analysis of trigeminal ganglia from human cadavers without active evidence of VZV infection indicates that at least two VZV genes, ORF29 and ORF62, are expressed during viral latency. These genes are expressed exclusively in non- neuronal (satellite) cells. In contrast, other VZV genes, ORF10, ORF28, and ORF61, are not expressed during latency. Therefore, the mechanism of VZV latency in the central nervous system of humans is markedly different from that of the most closely human herpesvirus, herpes simplex virus.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Allergy and Infectious Diseases (NIAID)
• Type: Intramural Research (Z01)
• Project #: 1Z01AI000430-09
• Application #: 3768792
• Support Year: 9
• Fiscal Year: 1993

Institution

• Name: National Institute of Allergy and Infectious Diseases
• Country: United States

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