Genistein treatment of cells inhibits arenavirus infection.
Arenaviridae is a family of enveloped viruses some of which are capable of causing hemorrhagic fever syndromes in humans. In this report, we demonstrate that treatment of host cells with the tyrosine kinase inhibitor genistein inhibits infection of cells with the New World arenavirus Pichindé (PICV). The greatest degree of inhibition was observed in pre-treated target cells, but modest inhibition of infection was also seen when drug was added to cultures up to 48h after infection. We show that PICV-induced phosphorylation of the activating transcription factor-2 protein (ATF-2) and cyclic adenosine monophosphate response element binding protein (CREB) is inhibited following genistein treatment. Lastly, genistein treatment also inhibited transduction of cells with pseudotyped retrovirus particles expressing envelope proteins of the Old World arenavirus Lassa virus. These results demonstrate that kinase activity is required for arenavirus infection and that therapeutics designed to inhibit kinase activity should be explored.
Vela
Eric M
EM
Department of Pathology, Center for Biodefense and Emerging Infectious Diseases, Institute for Human Infections and Immunity, The University of Texas Medical Branch, Galveston, TX 77555, United States. emvela@utmb.edu
Bowick
Gavin C
GC
Herzog
Norbert K
NK
Aronson
Judith F
JF
D051698:Activating Transcription Factor 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D007836:Lassa virus / Q000187:drug effects; D009698:Nucleoproteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D018052:Pichinde virus / Q000187:drug effects*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects
C497105:ATF2 protein, human; D051698:Activating Transcription Factor 2; D017362:Cyclic AMP Response Element-Binding Protein; D009698:Nucleoproteins; D047428:Protein Kinase Inhibitors; D019833:Genistein; D048049:Extracellular Signal-Regulated MAP Kinases