THE CARBOXYL-TERMINUS OF THE MURINE MYD116 GENE SUBSTITUTES FOR THE CORRESPONDING DOMAIN OF THE GAMMA(1)34.5 GENE OF HERPES-SIMPLEX VIRUS TO PRECLUDE THE PREMATURE SHUTOFF OF TOTAL PROTEIN-SYNTHESIS IN INFECTED HUMAN-CELLS

The herpes simplex virus 1 mutants from which both copies of the gamma (1)34.5 gene had been deleted trigger total shutoff of protein synthes is in human neuroblastoma cells and human foreskin fibroblasts but not in African green monkey (Vero) cells. The carboxyl-terminal 64 amino acids of gamma(1)34.5 are homologous to the corresponding domain of My D116, a murine myeloid differentiation primary responsive gene. The ca rboxyl-terminal domain of gamma(1)34.5 is required to preclude the shu toff of protein synthesis (J. Chou and B. Roizman, Proc. Natl. Acad, S ci, USA 91:5247-5251, 1994). We report that in-frame substitution of t he carboxyl terminus of gamma(1)34.5 with the corresponding domain of MyD116 in the context of the viral genome restored the ability of gamm a(1)34.5 to preclude premature shutoff of protein synthesis in both ne uroblastoma cells and in human foreskin fibroblasts. The results sugge st that (i) in the course of its evolution, the virus ''borrowed'' a g ene fragment to preclude a cell response to infection and (ii) the car boxyl terminus of MyD116 and its family of genes known as GADD34 may h ave a similar function(s) in cells stressed by growth arrest, DNA dama ge, and differentiation and in herpes simplex virus infection.