Aurintricarboxylic acid inhibits the early stage of vaccinia virus replication by targeting both cellular and viral factors.
Aurintricarboxylic acid (ATA) has been shown to inhibit the replication of viruses from several different families, including human immunodeficiency virus, vesicular stomatitis virus, and the coronavirus causing severe acute respiratory syndrome. This study characterizes the inhibitory effect of ATA on vaccinia virus replication in HeLa, Huh7, and AD293 cells. Vaccinia virus replication is significantly abrogated upon ATA treatment, which is associated with the inhibition of early viral gene transcription. This inhibitory effect may be attributed to two findings. First, ATA blocks the phosphorylation of extracellular signal-regulated kinase 1/2, an event shown to be essential for vaccinia virus replication. Second, ATA inhibits the phosphatase activity of the viral enzyme H1L, which is required to initiate viral transcription. Thus, ATA inhibits vaccinia virus replication by targeting both cellular and viral factors essential for the early stage of replication.
Myskiw
Chad
C
National Microbiology Laboratory, Canadian Science Centre for Human and Animal Health, 1015 Arlington Street, Winnipeg, Manitoba R3E 3R2, Canada.
Deschambault
Yvon
Y
Jefferies
Kristel
K
He
Runtao
R
Cao
Jingxin
J
D000998:Antiviral Agents / Q000494:pharmacology*; D001312:Aurintricarboxylic Acid / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008113:Liver Neoplasms / Q000473:pathology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D014616:Vaccinia virus / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D010948:Viral Plaque Assay; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D001312:Aurintricarboxylic Acid; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D010749:Phosphoprotein Phosphatases