Aphidicolin inhibits in vitro the activity of pseudorabies virus (PRV) DNA polymerase and in vivo the viral proliferation.
We have purified and characterized Pseudorabies virus (PRV) DNA polymerase from infected TK- mouse cells. PRV DNA polymerase has a 3'- > 5' exonuclease activity; it is stimulated by ionic strength, requires magnesium for optimal activity and it is more sensitive to aphidicolin than eukaryotic and HSV-1 replicative DNA polymerases. Aphidicolin inhibits in vitro PRV DNA polymerase competitively with respect to dCTP with a Ki of 0.06 microM and completely blocks viral growth in vivo at 4.4 microM. The high sensitivity to aphidicolin of animal herpesvirus DNA polymerases might allow a topical use of this drug in the treatment of animal herpesvirus keratitis and stomatitis.
Verri
A
A
Istituto di Genetica Biochimica ed Evoluzionistica, CNR, Pavia, Italy.
Maga
G
G
Spadari
S
S
Ponti
W
W
Strosselli
S
S
Bonizzi
L
L
Rocchi
M
M
Poli
G
G
Focher
F
F
D000818:Animals; D016590:Aphidicolin / Q000494:pharmacology*; D002460:Cell Line; D011558:Herpesvirus 1, Suid / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D051379:Mice; D019384:Nucleic Acid Synthesis Inhibitors; D014779:Virus Replication / Q000187:drug effects
D019384:Nucleic Acid Synthesis Inhibitors; D016590:Aphidicolin