TY - JOUR
T1 - The replication of viral and cellular DNA in human herpesvirus 6-infected cells
AU - Di Luca, Dario
AU - Katsafanas, George
AU - Schirmer, Eric C.
AU - Balachandran, N.
AU - Frenkel, Niza
N1 - Funding Information:
Health Service Grant Al24224 from the National Institutes of Health and a grant from Wesley Foundation of Wichita, Kansas,
Funding Information:
We thank Dr. Carlos Lopez and Ms. Karen Sanderlin (CDC) for the gift of HHV-6 strain 229 and for communicating to us the initial procedures of virus propagation. D.D.L. was the recipient of an A.I.R.C. (Associazione ltaliana per la Ricerca sul Cancro) fellowship. Work performed at the University of Kansas was supported by Public
PY - 1990/3
Y1 - 1990/3
N2 - Human herpesvirus 6 (HHV-6) is a newly identified lymphotropic herpesvirus. We have analyzed viral and host DNA replication in peripheral blood lymphocytes infected in the absence of drugs or infected in the presence of phosphonoacetic acid (PAA) or acyclovir (ACV). The results revealed the following: (i) Infection with HHV-6 resulted in the shutoff of host DNA replication. (ii) PAA at concentrations of 100 and 300 μg/ml significantly reduced virus replication. The drug inhibited viral DNA replication, whereas host cell DNA replication was not affected. This strongly suggests that HHV-6 encodes a PAA sensitive viral DNA polymerase. (iii) ACV at 20 μM did not interfere with virus production and virus spread. ACV at 100 μM only partly interfered with virus replication, whereas at 400 μM the block was more complete. Viral DNA replication was not affected by ACV at 20 μM. However, approximately 60 and 85% inhibition in viral DNA replication was observed in the presence of 100 and 400 μM of ACV. (iv) Assays for viral thymidine kinase (TK) revealed no significant increase in TK activity, whereas increased TK activity was noted following infection of the same peripheral blood lymphocytes with herpes simplex virus. Thus, either HHV-6 does not encode a tk enzyme which can phosphorylate ACV or the inefficient block may reflect lower sensitivity of the HHV-6 DNA polymerase to the drug.
AB - Human herpesvirus 6 (HHV-6) is a newly identified lymphotropic herpesvirus. We have analyzed viral and host DNA replication in peripheral blood lymphocytes infected in the absence of drugs or infected in the presence of phosphonoacetic acid (PAA) or acyclovir (ACV). The results revealed the following: (i) Infection with HHV-6 resulted in the shutoff of host DNA replication. (ii) PAA at concentrations of 100 and 300 μg/ml significantly reduced virus replication. The drug inhibited viral DNA replication, whereas host cell DNA replication was not affected. This strongly suggests that HHV-6 encodes a PAA sensitive viral DNA polymerase. (iii) ACV at 20 μM did not interfere with virus production and virus spread. ACV at 100 μM only partly interfered with virus replication, whereas at 400 μM the block was more complete. Viral DNA replication was not affected by ACV at 20 μM. However, approximately 60 and 85% inhibition in viral DNA replication was observed in the presence of 100 and 400 μM of ACV. (iv) Assays for viral thymidine kinase (TK) revealed no significant increase in TK activity, whereas increased TK activity was noted following infection of the same peripheral blood lymphocytes with herpes simplex virus. Thus, either HHV-6 does not encode a tk enzyme which can phosphorylate ACV or the inefficient block may reflect lower sensitivity of the HHV-6 DNA polymerase to the drug.
UR - http://www.scopus.com/inward/record.url?scp=0025268739&partnerID=8YFLogxK
U2 - 10.1016/0042-6822(90)90200-B
DO - 10.1016/0042-6822(90)90200-B
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AN - SCOPUS:0025268739
VL - 175
SP - 199
EP - 210
JO - Virology
JF - Virology
SN - 0042-6822
IS - 1
ER -