TY - JOUR
T1 - Human cytomegalovirus requires cellular deoxycytidylate deaminase for replication in quiescent cells
AU - Gribaudo, Giorgio
AU - Riera, Ludovica
AU - Caposio, Patrizia
AU - Maley, Frank
AU - Landolfo, Santo
PY - 2003/6/1
Y1 - 2003/6/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0038315265&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0038315265&partnerID=8YFLogxK
U2 - 10.1099/vir.0.18979-0
DO - 10.1099/vir.0.18979-0
M3 - Article
C2 - 12771412
AN - SCOPUS:0038315265
SN - 0022-1317
VL - 84
SP - 1437
EP - 1441
JO - Journal of General Virology
JF - Journal of General Virology
IS - 6
ER -