Simian varicella virus (SVV) infection of primates and varicella-zoster virus (VZV) infection of humans share clinical, pathological, immunological and virological features. Both viruses become latent in ganglia at all levels of the neuraxis. Unlike any animal model of varicella latency, both VZV and SVV reactivate from latently infected ganglia of their natural host. Furthermore, human ganglia cannot be removed during life, while monkey ganglia containing latently infected or reactivated SVV can be analyzed before death in anaesthetized monkeys. These features provide a rationale for our hypothesis that the physical state of latent SVV in ganglia of monkeys naturally infected with SVV parallels VZV latency in humans, and that this model can be used to test immunosuppression as an effector ofvaricella reactivation. To test our hypothesis, we will identify all SVV genes that are transcribed and translated in intently infected monkey ganglia as wall as identify the calls within Intently infected monkey ganglia that harbor SVV. Also, based on clinical protocols currently being used that result in VZV reactivation in humans, we will analyze reactivation of latent SVV induced by x-irradiation, immunosuppressive drugs, and anti-inflammatory drug therapy, separately and in combinations. A more comprehensive knowledge of the physical state of latent and reactivated simian varicella virus, gained by testing our hypothesis, will lead to experiments designed to understand and prevent the cascade of events leading to human varicella reactivation, a cause of serious neurologic disease, particularly in the rapidly increasing elderly and immunocompromised populations.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Program Projects (P01)
Project #
2P01NS032623-16A1
Application #
6746018
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Project Start
2003-12-01
Project End
2008-11-30
Budget Start
2003-12-01
Budget End
2005-01-31
Support Year
16
Fiscal Year
2004
Total Cost
$342,381
Indirect Cost
Name
University of Colorado Denver
Department
Type
DUNS #
041096314
City
Aurora
State
CO
Country
United States
Zip Code
80045
Cohrs, Randall J; Lee, Katherine S; Beach, Addilynn et al. (2017) Targeted Genome Sequencing Reveals Varicella-Zoster Virus Open Reading Frame 12 Deletion. J Virol 91:
Ouwendijk, Werner J D; van Veen, Suzanne; Mahalingam, Ravi et al. (2017) Simian varicella virus inhibits the interferon gamma signalling pathway. J Gen Virol :
Ouwendijk, Werner J D; Getu, Sarah; Mahalingam, Ravi et al. (2016) Characterization of the immune response in ganglia after primary simian varicella virus infection. J Neurovirol 22:376-88
Birlea, Marius; Owens, Gregory P; Eshleman, Emily M et al. (2013) Human anti-varicella-zoster virus (VZV) recombinant monoclonal antibody produced after Zostavax immunization recognizes the gH/gL complex and neutralizes VZV infection. J Virol 87:415-21
Mueller, Niklaus H; Bos, Nathan L; Seitz, Scott et al. (2012) Recombinant monoclonal antibody recognizes a unique epitope on varicella-zoster virus immediate-early 63 protein. J Virol 86:6345-9
Nagel, Maria A; Bert, Robert J; Gilden, Don (2012) Raeder syndrome produced by extension of chronic inflammation to the internal carotid artery. Neurology 79:1296-7
Wolf, James; Nagel, Maria A; Mahalingam, Ravi et al. (2012) Chronic active varicella zoster virus infection. Neurology 79:828-9
Brennan, Kathryn M; Galban-Horcajo, Francesc; Rinaldi, Simon et al. (2011) Lipid arrays identify myelin-derived lipids and lipid complexes as prominent targets for oligoclonal band antibodies in multiple sclerosis. J Neuroimmunol 238:87-95
Azarkh, Yevgeniy; Gilden, Don; Cohrs, Randall J (2010) Molecular characterization of varicella zoster virus in latently infected human ganglia: physical state and abundance of VZV DNA, Quantitation of viral transcripts and detection of VZV-specific proteins. Curr Top Microbiol Immunol 342:229-41
Sargsyan, S A; Shearer, A J; Ritchie, A M et al. (2010) Absence of Epstein-Barr virus in the brain and CSF of patients with multiple sclerosis. Neurology 74:1127-35

Showing the most recent 10 out of 146 publications