Cocaine potentiates the switch between latency and replication of Epstein-Barr virus in Raji cells.
This paper shows that cocaine amplifies Epstein-Barr virus (EBV) reactivation in Raji cells. Its effect on early viral protein synthesis was maximal when it was added with 12-O-tetradecanoyl phorbol-13-acetate (TPA) plus n-butyrate, but nil when added alone. The enhancing effect of cocaine on early replicative stages of latent EBV was associated with an increase of Ca(2+) mobilization induced by the drug and with an induction of cellular protein phosphorylation in chemicals and cocaine-treated Raji cells. Cocaine also acted synergistically with TPA and n-butyrate to induce Z Epstein-Barr replication activator (ZEBRA), a nuclear phosphoprotein responsible for the activation of early viral gene expression. These findings provide the first evidence that cocaine may represent an important co-factor in the reactivation of early stages of latent EBV infection.
Di Francesco
P
P
Department of Experimental Medicine and Biochemical Sciences, Microbiology, University of Rome Tor Vergata, Rome, Italy. difra@uniroma2.it
Lisi
A
A
Rieti
S
S
Manni
V
V
Grimaldi
S
S
Garaci
E
E
D001692:Biological Transport / Q000187:drug effects; D002087:Butyrates / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002273:Carcinogens / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D004357:Drug Synergism; D004854:Herpesvirus 4, Human / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015534:Trans-Activators / Q000096:biosynthesis; D014407:Tumor Cells, Cultured; D014764:Viral Proteins; D017735:Virus Latency / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects*
C063676:BZLF1 protein, Herpesvirus 4, Human; D002087:Butyrates; D002273:Carcinogens; D004268:DNA-Binding Proteins; D015534:Trans-Activators; D014764:Viral Proteins; D003042:Cocaine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium