Molecular Biology of Varicella Zoster Virus Infection

Cohen, Jeffrey

Abstract

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 molecular basis for latency of VZV and for attenuation of the Oka vaccine strain of VZV.We have developed a small animal model for VZV latency by infecting neonatal rats with the virus. These animals become latently infected, and analysis of the their nervous system shows viral DNA is present 6 weeks after infection. A VZV gene (ORF21) that has been associated with latent infection in humans is expressed 6 weeks after infection, while another gene (ORF40) not associated with latency is not expressed. To begin to understand the molecular basis for attenutation of the Oka vaccine strain of VZV, we have sequenced a large portion of the Oka vaccine strain and compared it to the sequence of the parental (wild-type) Oka strain. Several differences were noted in one VZV gene (ORF62)and tests based on differences in this gene successfully distinguished the Oka vaccine strain from its wild-type parent. These changes remained stable after passage of the virus in humans.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Allergy and Infectious Diseases (NIAID)
• Type: Intramural Research (Z01)
• Project #: 1Z01AI000430-16
• Application #: 6431564
• Study Section: (LCI)
• Support Year: 16
• Fiscal Year: 2000

Institution

• Name: Niaid Extramural Activities
• 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