Virologica Sinica

, Volume 28, Issue 2, pp 81–91

Analysis of oseltamivir resistance substitutions in influenza virus glycoprotein neuraminidase using a lentivirus-based surrogate assay system

  • Jennifer Tisoncik-Go
  • Katie S. Cordero
  • Lijun Rong
Research Article

DOI: 10.1007/s12250-013-3307-8

Cite this article as:
Tisoncik-Go, J., Cordero, K.S. & Rong, L. Virol. Sin. (2013) 28: 81. doi:10.1007/s12250-013-3307-8

Abstract

Influenza A virus poses a great threat to global health, and oseltamivir (trade marked as Tamiflu), which targets influenza surface glycoprotein neuraminidase (NA), is used clinically as a major anti-influenza treatment. However, certain substitutions in NA can render an influenza virus resistant to this drug. In this study, using a lentiviral pseudotyping system, which alleviates the safety concerns of studying highly pathogenic influenza viruses such as avian influenza H5N1, that utilizes influenza surface glycoproteins (hemagglutinin or HA, and NA) and an HIV-core combined with a luciferase reporter gene as a surrogate assay, we first assessed the functionality of NA by measuring pseudovirion release in the absence or presence of oseltamivir. We demonstrated that oseltamivir displays a dose-dependent inhibition on NA activity. In contrast, a mutant NA (H274Y) is more resistant to oseltamivir treatment. In addition, the effects of several previously reported substitution NA mutants were examined as well. Our results demonstrate that this lentivirus-based pseudotyping system provides a quick, safe, and effective way to assess resistance to neuraminidase inhibitors. And we believe that as new mutations appear in influenza isolates, their impact on the effectiveness of current and future anti-NA can be quickly and reliably evaluated by this assay.

Keywords

Influenza virus Neuraminidase (NA) Oseltamivir Drug resistance 

Copyright information

© Wuhan Institute of Virology, CAS and Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Jennifer Tisoncik-Go
    • 1
  • Katie S. Cordero
    • 1
  • Lijun Rong
    • 1
  1. 1.Department of Microbiology and Immunology, College of MedicineUniversity of Illinois at ChicagoChicagoUSA
  2. 2.Department of MicrobiologyUniversity of WashingtonSeattleUSA

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