Regulation of glycoprotein D synthesis of herpes simplex virus 1 by alpha 4 protein, the major regulatory protein of the virus, in stably transformed cell lines: effect of the relative gene copy numbers.
Earlier studies concerning gamma 1 gene regulation by the alpha 4 protein, the major regulatory protein of herpes simplex virus 1 (HSV-1), in stably transformed cell lines, reported conflicting results, i.e., alpha 4 protein positively regulated the gamma 1 gB gene in alpha 4/gB cells, while it negatively regulated the gamma 1 gD gene in alpha 4/BJ cells. Both cell lines were derived from a common parental cell line alpha 4/c 113 that contains 1 copy of the alpha 4 gene, and the only apparent difference between them was the relative copy number of the gB and gD sequences (1 and 30-50, respectively) resident in the cell genome. We investigated this disparity by constructing a cell line (BA 4) that contains one copy each of the alpha 4 and gamma 1 gD sequences, by fusion of alpha 4/c 113 and BJt cells, containing and expressing respectively 1 copy of the alpha 4 and gD genes. BA 4 cells constitutively expressed both the alpha 4, gD genes inherited from the parental cell lines (alpha 4/c 113 and BJt). In BA 4 cells that alpha 4 protein positively regulates the gD gene as evidenced from (i) higher levels of gD expression than the parental BJt cells lacking the alpha 4 gene, and (ii) significant decrease in gD expression under conditions that render the alpha 4 protein produced in BA 4 cells non-functional. In addition the gamma 2gG gene contained within the DNA fragment encoding the gD gene, is also expressed in BA 4 cells. On the basis of these data, we propose that gamma gene regulation by the alpha 4 protein is affected by the relative copy number of these genes, resident in the cell genome.
Department of Biology, Aristotelian University, Thessaloniki, Greece.
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A
Sivropoulou
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M
Arsenakis
D002459:Cell Fusion; D002461:Cell Line, Transformed; D005784:Gene Amplification; D015967:Gene Expression Regulation, Viral; D005814:Genes, Viral; D017874:Immediate-Early Proteins; D018139:Simplexvirus / Q000235:genetics / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000096:biosynthesis* / Q000235:genetics; D054334:Viral Regulatory and Accessory Proteins / Q000502:physiology*
D017874:Immediate-Early Proteins; D014759:Viral Envelope Proteins; D054334:Viral Regulatory and Accessory Proteins; C039447:glycoprotein D, Human herpesvirus 1; C048925:herpes simplex virus, type 1 protein ICP4