Abstract
The mechanisms involved in the herpes simplex virus type 1 (HSV-1) latency-reactivation cycle are not fully understood. The latency-associated transcript (LAT) is the only HSV-1 RNA abundantly detected during neuronal latency. LAT plays a significant role in latency because LAT(−) mutants have a reduced reactivation phenotype. Several novel viral transcripts have been identified within the LAT locus, including UOL, which is located just upstream of LAT. The authors report here on a mutant, ΔUOL, which has a 437-nucleotide deletion that deletes most of UOL. ΔUOL replicated similarly to its wild-type parental McKrae HSV-1 strain in infected cells, the eyes, trigeminal ganglia, and brains of mice and rabbits. It was indistinguishable from wild-type virus as regards explant-induced reactivation in mice, and spontaneous reactivation in rabbits. In contrast, ΔUOL was significantly less virulent in mice. Thus, UOL appears to be dispensable for the wild-type reactivation phenotype while appearing to play a role in neurovirulence in ocularly infected animals.
Keywords:
This work was supported by Research to Prevent Blindness, The Discovery Fund for Eye Research, The Henry L. Guenther Foundation, Public Health Service grant NIH EY13191, and UCI COM grants. Dr. Wechsler is an RPB Senior Scientific Investigator. The authors thank Jennifer Cooper for her technical advice in mouse TG explant reactivation assays. They also thank Anita Avery for her excellent assistance with tissue culture and virus titrations. Received 16 July 2005; revised 10 October 2005; accepted 25 November 2005.