The Role of Marek’s Disease Virus UL12 and UL29 in DNA Recombination and the Virus Lifecycle

Abstract

Marek’s disease virus (MDV) is an oncogenic alphaherpesvirus that infects chickens and integrates its genome into the telomeres of latently infected cells. MDV encodes two proteins, UL12 and UL29 (ICP8), that are conserved among herpesviruses and could facilitate virus integration. The orthologues of UL12 and UL29 in herpes simplex virus 1 (HSV-1) possess exonuclease and single strand DNA-binding activity, respectively, and facilitate DNA recombination; however, the role of both proteins in the MDV lifecycle remains elusive. To determine if UL12 and/or UL29 are involved in virus replication, we abrogated their expression in the very virulent RB-1B strain. Abrogation of either UL12 or UL29 resulted in a severe impairment of virus replication. We also demonstrated that MDV UL12 can aid in single strand annealing DNA repair, using a well-established reporter cell line. Finally, we assessed the role of UL12 and UL29 in MDV integration and maintenance of the latent virus genome. We could demonstrate that knockdown of UL12 and UL29 does not interfere with the establishment or maintenance of latency. Our data therefore shed light on the role of MDV UL12 and UL29 in MDV replication, DNA repair, and maintenance of the latent virus genome.