Use of a rodent model to show that varicella-zoster virus ORF61 is dispensable for establishment of latency.

Abstract

Varicella-zoster virus (VZV) results in a latent infection in humans after primary infection. Latency has also been established in guinea pigs and rats after inoculation with the virus. It was found that infection of cotton rats with the Oka vaccine strain of VZV results in a latent infection. To begin to identify which genes are required for latency, we infected cotton rats with VZV strain Oka that is deleted for ORF61. ORF61 protein transactivates certain VZV promoters and enhances the infectivity of viral DNA in transient transfections. Deletion of ORF61 results in abnormal syncytia and impairs the growth of VZV in vitro. Inoculation of cotton rats with ORF61-deleted Oka virus resulted in latent VZV infection in the nervous system similar to that seen for animals infected with parental virus. Thus, the cotton rat can be used to study the ability of mutants in the Oka vaccine strain of VZV to establish latent infection.