Human cytomegalovirus requires cellular deoxycytidylate deaminase for replication in quiescent cells

Giorgio Gribaudo, Ludovica Riera, Patrizia Caposio, Frank Maley, Santo Landolfo

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

We have previously observed that the expression of two thymidylate biosynthesis enzymes, dihydrofolate reductase and thymidylate synthase (TS), is upregulated in quiescent human fibroblasts infected with human cytomegalovirus (HCMV). Here, we have demonstrated that HCMV increases expression of the cellular deoxycytidylate deaminase (dCMP deaminase), which provides the substrate for TS by converting dCMP to dUMP. We observed an increase in dCMP deaminase protein levels, whereas deoxyuridine triphosphatase (dUTPase), another cellular enzyme that may provide dUMP by hydrolysing dUTP, was undetectable. The essential requirement of cellular dCMP deaminase for productive HCMV replication was further emphasized by showing that a precursor of a potent dCMP deaminase inhibitor, zebularine, suppressed virus replication and DNA synthesis. These results suggest that HCMV exploits the host's dCMP deaminase activity to replicate in quiescent cells.

Original languageEnglish (US)
Pages (from-to)1437-1441
Number of pages5
JournalJournal of General Virology
Volume84
Issue number6
DOIs
StatePublished - Jun 1 2003
Externally publishedYes

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DCMP Deaminase
Cytomegalovirus
pyrimidin-2-one beta-ribofuranoside
Thymidylate Synthase
Deoxyuridine
Enzymes
Virus Replication
Fibroblasts
DNA

ASJC Scopus subject areas

  • Virology
  • Immunology

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Human cytomegalovirus requires cellular deoxycytidylate deaminase for replication in quiescent cells. / Gribaudo, Giorgio; Riera, Ludovica; Caposio, Patrizia; Maley, Frank; Landolfo, Santo.

In: Journal of General Virology, Vol. 84, No. 6, 01.06.2003, p. 1437-1441.

Research output: Contribution to journalArticle

Gribaudo, Giorgio ; Riera, Ludovica ; Caposio, Patrizia ; Maley, Frank ; Landolfo, Santo. / Human cytomegalovirus requires cellular deoxycytidylate deaminase for replication in quiescent cells. In: Journal of General Virology. 2003 ; Vol. 84, No. 6. pp. 1437-1441.
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