Dr. Gilden has devoted 35 years to studying the molecular pathogenesis of VZV infection. He was the first to prove that VZV is latent in normal human ganglia, work that was accomplished before PCR amplification of viral DNA had been developed. His laboratory has analyzed the physical state of VZV nucleic acid and gene expression in >6000 latently infected human ganglia from >700 randomly autopsied subjects. Several resulting milestones include: the first detection of the entire viral genome in human ganglia along the entire neuraxis; the first demonstration of the circular configuration and association of latent VZV DNA with histones; the first demonstration of the highly variable abundance of latent VZV; the first identification of multiple VZV transcripts during latency; and one of the first two demonstrations that VZV is latent exclusively in neurons of human ganglia. Dr. Gilden's correlative clinical-virological studies with VZV identified zoster sine herpete (shingles pain without rash) as a true nosologic entity and discovered that VZV "encephalitis" is primarily a vasculopathy with virus production in cerebral arteries rather than in brain parenchyma. His laboratory has shown that detection of anti-VZV IgG in CSF is a significantly more sensitive indicator of VZV vasculopathy and VZV myelopathy than detection of VZV DNA. He further demonstrated that VZV vasculopathy and VZV infection of the spinal cord, including recurrent myelitis, often manifest without rash. Multiple patients have already benefited from therapy based on improved clinical and virological diagnosis developed by his laboratory, a scenario likely to continue as his group documents VZV infection in the temporal arteries of patients with giant cell arteritis (GCA). In the past 5 years, his group has developed a model of non-productive VZV infection in neurons in vitro  that will allow studies of mechanisms of VZV reactivation.