Partial substitution of the functions of the herpes simplex virus 1 U(L)13 gene by the human cytomegalovirus U(L)97 gene.
The predicted amino acid sequence of the human cytomegalovirus U(L)97 protein bears partial homology to the herpes simplex virus 1 U(L)13 protein, especially in regions that are homologous to conserved domains characteristic of protein kinases. Earlier studies showed that U(L)13 mediated the posttranslational processing of several herpes simplex virus 1 proteins including ICP22. Whereas no kinase activity has been specifically attributed to U(L)13, it has been shown that U(L)97 can phosphorylate ganciclovir. To examine whether U(L)97 can substitute for U(L)13, we constructed a herpes simplex virus 1 recombinant virus, R4970, in which U(L)13 was replaced by U(L)97 and in addition, the thymidine kinase gene was deleted. Characterization of this recombinant virus showed the following: (1) The recombinant virus grew as well as the wild-type virus in BHKTK+ cells, which restricted the growth of the U(L)13 virus. (2) U(L)97 could partially mediate the posttranslational modification of HSV-1 ICP22. This modification correlated with the restoration of the amounts of ICP0 and U(S)11 proteins, which were down regulated in the U(L)13- virus-infected cells. (3) The recombinant virus was sensitive to ganciclovir in Vero- and KHOS-infected cells but not in the 143 thymidine kinase minus cells derived from KHOS cells. Vero cells infected with this recombinant virus phosphorylated ganciclovir. We conclude that U(L)97 partially compensates for U(L)13 functions.
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The Marjorie B. Kovler Viral Oncology Laboratories, University of Chicago, Illinois 60637, USA.
Talarico
C
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Burnette
T C
TC
Biron
K
K
Roizman
B
B
D000818:Animals; D002522:Chlorocebus aethiops; D003587:Cytomegalovirus / Q000235:genetics*; D004274:DNA, Recombinant; D005814:Genes, Viral; D006801:Humans; D016865:Reassortant Viruses / Q000235:genetics; D018139:Simplexvirus / Q000235:genetics*; D014709:Vero Cells
D004274:DNA, Recombinant