Herpes simplex virus type 1 gene UL14: Phenotype of a null mutant and identification of the encoded protein

Herpes simplex virus type 1 (HSV-1) gene UL14 is located between divergentl y transcribed genes UL13 and UL15 and overlaps the promoters for both of th ese genes. UL14 also exhibits a substantial overlap of its coding region wi th that of UL13, It is one of the few HSV-1 genes for which a phenotype and protein product have not been described, Using mass spectrometric and immu nological approaches, we demonstrated that the UL14 protein is a minor comp onent of the virion tegument of 32 kDa which is expressed late in infection , In infected cells, the UL14 protein was detected in the nucleus at discre te sites within electron-dense nuclear bodies and in the cytoplasm initiall y in a diffuse distribution and then at discrete sites. Some of the UL14 pr otein was phosphorylated, A mutant with a 4-bp deletion in the central regi on of UL14 failed to produce the UL14 protein and generated small plaques. The mutant exhibited an extended growth cycle at low multiplicity of infect ion and appeared to be compromised in efficient transit of virus particles from the infected cell. In mice injected intracranially, the 50% lethal dos e of the mutant was reduced more than 30,000-fold. Recovery of the mutant f rom the latently infected sacral ganglia of mice injected peripherally was significantly less than that of wild-type virus, suggesting a marked defect in the establishment of, or reactivation from, latent infection.