Characterization of human H1N1 influenza virus variants selected in vitro with zanamivir in the presence of sialic acid-containing molecules
- Resource Type
- Article
- Authors
- Giannecchini, Simone; Campitelli, Laura; Bandini, Giacomo; Donatelli, Isabella; Azzi, Alberta
- Source
- Virus Research. Nov2007, Vol. 129 Issue 2, p241-245. 5p.
- Subject
- *INFLUENZA viruses
*SIALIC acids
*NEURAMINIDASE
*RESPIRATORY infections
- Language
- ISSN
- 0168-1702
Abstract: Understanding the molecular mechanisms of influenza virus resistance to neuraminidase inhibitors is a main concern for their clinical use. In an attempt to reproduce in vivo selective conditions where influenza virus resistance to neuraminidase inhibitors can occur the zanamivir selection of an A/H1N1 influenza virus strain was carried out in Madin-Darby canine kidney cells performed in the presence or absence of sialic acid-containing inhibitor analogues that act as virus decoy receptors. The zanamivir-selected variants passaged in the presence of sialic acid-containing molecules resembling the human-like virus receptor lost the ability to bind red blood cells. Furthermore, whereas all zanamivir-selected variants exhibited a robust reduction in susceptibility to zanamivir in plaque assays only those obtained after extensive passages acquired a powerful neuraminidase enzyme resistance to zanamivir and oseltamivir. Evidence that balanced neuraminidase and hemagglutinin activities mediated by mutations induced during selection could play a role in the decrease of virus replication susceptibility to zanamivir is reported. [Copyright &y& Elsevier]