Characterization of a trypsin-dependent avian influenza H5N1-pseudotyped HIV vector system for high throughput screening of inhibitory molecules

Zhujun Ao, Ami Patel, Kaylie Tran, Xinying He, Keith Fowke, Kevin Coombs, Darwyn Kobasa, Gary Kobinger, Xiaojian Yao

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

In this study, we have generated and characterized an avian influenza H5N1 hemagglutinin (HA), neuraminidase (NA) and M2 ion channel pseudotyped HIV-based vector system (HaNaM-pseudotyped HIV vector). The cleavage site of the HA protein was modified to necessitate trypsin-dependent maturation of the glycoprotein. HA, NA and M2 were efficiently incorporated in HIV vector particles which could transduce different cell lines in a trypsin-dependent manner. Results also showed that the presence of avian influenza M2 and NA proteins maximized both vector production and transduction and that transduction was highly sensitive to the specific NA inhibitor oseltamivir (Tamiflu). H5N1 HaNaM-pseudotyped HIV vector system was also adapted for cell-based high throughput screening of drug candidates against influenza virus infection, and its high sensitivity to the specific oseltamivir validates its potential utility in the identification of new influenza inhibitors. Overall, the trypsin-dependent H5N1-pseudotyped HIV vector can mimic avian influenza virus infection processes with sufficient precision to allow for the identification of new antivirals and to study avian influenza virus biology in a lower biosafety level laboratory environment.

Original languageEnglish (US)
Pages (from-to)12-18
Number of pages7
JournalAntiviral research
Volume79
Issue number1
DOIs
StatePublished - Jul 2008
Externally publishedYes

Keywords

  • Avian influenza virus
  • H5N1-pseudotyped HIV vector system
  • Hemagglutinin
  • M2 protein
  • Neuraminidase

ASJC Scopus subject areas

  • Pharmacology
  • Virology

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