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 synthesis 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 MyD116, a murine myeloid differentiation primary responsive gene. The carboxyl-terminal domain of gamma(1)34.5 is required to preclude the shutoff of protein synthesis (J. Chou and B. Roizman, Proc. Natl. Acad. Sci. USA 91:5247-5251, 1994). We report that in-frame substitution of the carboxyl terminus of gamma(1)34.5 with the corresponding domain of MyD116 in the context of the viral genome restored the ability of gamma(1)34.5 to preclude premature shutoff of protein synthesis in both neuroblastoma cells and in human foreskin fibroblasts. The results suggest that (i) in the course of its evolution, the virus "borrowed" a gene fragment to preclude a cell response to infection and (ii) the carboxyl terminus of MyD116 and its family of genes known as GADD34 may have a similar function(s) in cells stressed by growth arrest, DNA damage, and differentiation and in herpes simplex virus infection.
Marjorie B. Kovler Viral Oncology Laboratories, University of Chicago, Illinois 60637, USA.
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B
He
J
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Chou
D A
DA
Liebermann
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B
Hoffman
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B
Roizman
D000818:Animals; D000943:Antigens, Differentiation; D001483:Base Sequence; D001665:Binding Sites; D002264:Carboxylic Acids; D018797:Cell Cycle Proteins; D002460:Cell Line; D002522:Chlorocebus aethiops; D004274:DNA, Recombinant; D005347:Fibroblasts / Q000378:metabolism; D005814:Genes, Viral; D018259:Herpesvirus 1, Human / Q000235:genetics* / Q000502:physiology; D006801:Humans; D015151:Immunoblotting; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins; D009447:Neuroblastoma / Q000378:metabolism; D054645:Protein Phosphatase 1; D011506:Proteins / Q000235:genetics* / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014709:Vero Cells; D014764:Viral Proteins / Q000235:genetics* / Q000502:physiology
D000943:Antigens, Differentiation; D002264:Carboxylic Acids; D018797:Cell Cycle Proteins; D004274:DNA, Recombinant; D009363:Neoplasm Proteins; D011506:Proteins; D011993:Recombinant Fusion Proteins; D014764:Viral Proteins; C066469:gamma 34.5 protein, Human herpesvirus 1; C087519:PPP1R15A protein, human; D054645:Protein Phosphatase 1