Ravi Mahalingam, PhD

My laboratory at the University of Colorado Anschutz Medical Campus conducts cutting-edge research on varicella zoster virus (VZV) that has contributed significantly to our current understanding of the pathogenesis of virus latency and reactivation in humans. Having studied VZV for 25 years, I have more than 120 publications addressing important aspects of VZV infection. I was the first to demonstrate the presence of VZV DNA in multiple ganglia in humans along the entire neuraxis, results published in NEJM. Before the advent of real-time PCR, I used competitive PCR to demonstrate the low abundance (as few as 36 copies in 105 cells) of latent VZV DNA in human ganglia. In the next few years, I reported the expression of VZV ORF63 protein in the cytoplasm of human ganglia latently infected with VZV. I also demonstrated the persistence of VZV DNA in blood mononuclear cells from elderly patients with post-herpetic neuralgia. Later, I established an animal model of VZV latency in nonhuman primates infected with simian varicella virus (SVV). By generating SVV expressing green fluorescent protein (GFP), it became possible to identify cells infected with SVV both in vitro and in vivo; this virus is now used by multiple laboratories to study varicella pathogenesis and latency in experimentally infected animals. I later used this model to show that varicella enters ganglia before the appearance of rash. I sequenced the complete 125,000-base pair SVV genome, paving the way for molecular analysis of latency and reactivation. In 2007, I reported reactivation of SVV in immunosuppressed Cynomolgus monkeys, the pathogenic features of which are shared with patients with human VZV infection. Recently, I showed that SVV ORF63 is essential for viral replication in culture. Finally, I have mentored and trained numerous graduate students and postdoctoral fellows in Neurovirology.