Sarcelle
15.09.2007, 11:08
Characterization of human H1N1 influenza virus variants selected in vitro with zanamivir in the presence of sialic acid-containing molecules.
Virus Res. 2007 Aug 31;
http://www.ncbi.nlm.nih.gov:80/sites/entrez=cmd=Retrieve&db=PubMed&list_uids=17765996&dopt=AbstractPlus
Giannecchini S, Campitelli L, Bandini G, Donatelli I, Azzi A.
Virology Unit, Department of Public Health, University of Florence, I-50134 Florence, Italy.
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.
PMID: 17765996 [PubMed - as supplied by publisher]
Virus Res. 2007 Aug 31;
http://www.ncbi.nlm.nih.gov:80/sites/entrez=cmd=Retrieve&db=PubMed&list_uids=17765996&dopt=AbstractPlus
Giannecchini S, Campitelli L, Bandini G, Donatelli I, Azzi A.
Virology Unit, Department of Public Health, University of Florence, I-50134 Florence, Italy.
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.
PMID: 17765996 [PubMed - as supplied by publisher]