The JAK2 inhibitor AZD1480 inhibits hepatitis A virus replication in Huh7 cells

Biochem Biophys Res Commun. 2015 Mar 20;458(4):908-12. doi: 10.1016/j.bbrc.2015.02.058. Epub 2015 Feb 19.

Abstract

The JAK2 inhibitor AZD1480 has been reported to inhibit La protein expression. We previously demonstrated that the inhibition of La expression could inhibit hepatitis A virus (HAV) internal ribosomal entry-site (IRES)-mediated translation and HAV replication in vitro. In this study, we analyzed the effects of AZD1480 on HAV IRES-mediated translation and replication. HAV IRES-mediated translation in COS7-HAV-IRES cells was inhibited by 0.1-1 μM AZD1480, a dosage that did not affect cell viability. Results showed a significant reduction in intracellular HAV HA11-1299 genotype IIIA RNA levels in Huh7 cells treated with AZD1480. Furthermore, AZD1480 inhibited the expression of phosphorylated-(Tyr-705)-signal transducer and activator of transcription 3 (STAT3) and La in Huh7 cells. Therefore, we propose that AZD1480 can inhibit HAV IRES activity and HAV replication through the inhibition of the La protein.

Keywords: AZD1480; HAV; IRES; La; STAT3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology*
  • COS Cells
  • Cell Line
  • Chlorocebus aethiops
  • Hepatitis A / drug therapy*
  • Hepatitis A / metabolism
  • Hepatitis A / virology
  • Hepatitis A virus / drug effects*
  • Hepatitis A virus / genetics
  • Hepatitis A virus / physiology
  • Humans
  • Janus Kinase 2 / antagonists & inhibitors*
  • Pyrazoles / pharmacology*
  • Pyrimidines / pharmacology*
  • RNA, Viral / genetics
  • STAT3 Transcription Factor / metabolism
  • Virus Replication / drug effects*

Substances

  • AZD 1480
  • Antiviral Agents
  • Pyrazoles
  • Pyrimidines
  • RNA, Viral
  • STAT3 Transcription Factor
  • Janus Kinase 2