Varicella Virus Pathogenesis, Latency and Reactivation

Varicella Virus Pathogenesis, Latency and Reactivation

February 14, 2019


727 E. Tyler St.
Tempe, AZ 85281


Biodesign Institute, Auditorium

Date and Time

March 15, 2019, 12:00 pm (Length: 1 hour 0 minutes)

iCal Download

Ravi Mahalingam, PhD, Research Professor, Department of Neurology, University of Colorado, Anschutz Medical Campus

Varicella zoster virus (VZV), an exclusively human herpesvirus, causes chickenpox in children establishes latent infection in ganglia and reactivates decades later to produce zoster and associated neurological complications. Clinical, pathological, virological and immunological features of simian varicella virus (SVV) infection in nonhuman primates are similar to VZV infection in humans. Experimental infection of African green monkeys (AGM) with SVV has been used to demonstrate hematogenous spread of virus to ganglia in the absence of varicella rash.  During primary infection in AGMs, alveolar myeloid and T-cells are infected in lungs and during viremia SVV initially infects central memory and subsequently effector memory T-cells.  SVV is found in perivascular skin infiltrates composed of macrophages, dendritic cells, and memory T-cells, implicating hematogenous spread. In ganglia, SVV is found primarily in neurons and occasionally in memory T-cells adjacent to neurons suggesting the role of memory T-cells in dissemination. Intrabronchial inoculation of Rhesus macaques (RM) with SVV provides the most useful model to study latency. SVV DNA can be detected in saliva of RM concomitant with viremia. Immunosuppressive treatments of monkeys latently infected with SVV results in zoster. T-cell infiltration in ganglia with reactivated SVV in cynomolgus macaques correlates with expression of CXCL10 transcripts but not with SVV proteins. CD4-T cell depletion of RM latently infected with SVV results in reactivation and virus spread to multiple organs suggesting a critical role of CD4-T cell immunity in controlling latency. SVV infection of nonhuman primates provide a way to dissect, at the molecular level, the cascade of cellular and immune factors during primary infection as well as reactivation.