Viral drug sensitivity testing using quantitative PCR: Effect of tyrosine kinase inhibitors on polyomavirus BK replication

Parmjeet S. Randhawa, Noush A. Farasati, Yuchen Huang, Markus Y. Mapara, Ron Shapiro

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Our objective was to determine whether quantitative polymerase chain reaction (PCR) can be used to measure the effect of tyrosine kinase (TK) inhibition on polyomavirus BK (BKV) replication. The BKV was grown in a cell culture system. The rate of viral replication in the presence or absence of the drug being tested was assessed by amplifying the viral genome using primers directed against the viral capsid 1 protein. Dasatinib, erlotinib, gefitinib, imatinib, sunitinib, and sorafenib all showed antiviral activity at micromolar concentrations. The 50% effective concentration for erlotinib and sorafenib was within blood concentrations readily achieved in human subjects. Quantitative PCR is a convenient method for viral drug sensitivity testing for slow-growing viruses that do not readily produce cytopathic effect. TK inhibitors deserve further consideration as a potential therapeutic option for BKV-associated nephropathy and hemorrhagic cystitis.

Original languageEnglish
Pages (from-to)916-920
Number of pages5
JournalAmerican Journal of Clinical Pathology
Volume134
Issue number6
DOIs
StatePublished - Dec 2010
Externally publishedYes

Keywords

  • Bk polyomavirus
  • Infection
  • Tyrosine kinase

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