Dr. Arvin’s laboratory investigates the molecular virology of varicella zoster virus (VZV), a medically important human herpesvirus that causes varicella, establishes latency in sensory ganglia and can reactivate to cause herpes zoster. She has shown that VZV is both a neurotropic and a lymphotropic herpesvirus. She studies events in VZV pathogenesis in xenografts of human skin, T cell and dorsal root ganglia using the SCID mouse model developed by our group. The functions of VZV gene products and their subdomains and regulation of their expression by promoter elements targeted by viral and cellular transactivators are investigated by mutagenesis of the VZV genome using VZV cosmids and BACs; VZV recombinants are recovered if mutations are not lethal and are evaluated for the effects of targeted gene and promoter region deletions, point mutations and linker insertions on VZV replication in vitro and on VZV T cell, skin and neurotropism in the SCID mouse model. The mechanisms and pathways by which VZV overcomes innate antiviral cellular defenses or is modulated by these responses are investigated in vitro and in differentiated human cells within their intact tissue microenvironments in vivo. These studies are relevant for developing genetically engineered, live attenuated vaccines and antiviral drugs for VZV. In addition to basic research, our laboratory is involved with clinical studies to assess T cell responses to VZV induced by varicella vaccine in healthy and immunocompromised individuals, T cell immunity to influenza viruses and age-related effects on measles immunity in infants.