YEN HL, Ilyushina NA, Salomon R, Hoffmann E, et al. Neuraminidase Inhibitor Resistant Recombinant A/Vietnam/1203/04 (H5N1) Influenza Viruses Retain Their Replication Efficiency and Pathogenicity in Vitro and in Vivo. J Virol. 2007 Sep 12
Effective antiviral drugs are essential for early control of an influenza pandemic. It is therefore crucial to evaluate the possible threat posed by neuraminidase (NA) inhibitor-resistant influenza viruses with pandemic potential. Four NA mutations (E119G, H274Y, R292K, or N294S) that have been reported to confer resistance to NA inhibitors are each introduced into recombinant A/Vietnam/1203/04 (VN1203) H5N1 influenza virus. For comparison, the same mutations were introduced into recombinant A/Puerto Rico/8/34 (PR8) H1N1 influenza virus. The E119G and R292K mutations significantly compromised viral growth in vitro, but the H274Y and N294S mutations were stably maintained in VN1203 and PR8 viruses. In both backgrounds, the H274Y and N294S mutations conferred resistance to oseltamivir carboxylate (IC50 increase, > 250-fold and > 20-fold, respectively), and the N294S mutation reduced susceptibility to zanamivir (IC50 increase, > 3.0 fold). Although the H274Y and N294S mutations did not compromise the replication efficiency of VN1203 or PR8 viruses in vitro, these mutations slightly reduced the lethality of PR8 virus in mice. However, the VN1203 virus carrying either H274Y or N294S mutation exhibit similar lethality as the wild-type VN1203 virus. The different enzyme kinetic parameters (Vmax and Km) of avian-like VN1203 NA and human-like PR8 NA suggest that resistance-associated NA mutations can cause different levels of functional loss in NA glycoproteins of the same subtype. Our results suggest that NA inhibitor-resistant H5N1 variants may retain the high pathogenicity of the wild-type virus in mammalian species. Patients receiving NA inhibitors for H5N1 influenza virus infection should be closely monitored for the emergence of resistant variants.
See Also:
- http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=17855542&dopt=AbstractPlus
Latest articles in those days:
- Influenza D Virus Infection in China, 2022-2023 1 days ago
- Evidence of reassortment of avian influenza A (H2) viruses in Brazilian shorebirds 1 days ago
- Epitopes in the HA and NA of H5 and H7 avian influenza viruses that are important for antigenic drift 3 days ago
- Assessment of CD8+ T-cell mediated immunity in an influenza A(H3N2) human challenge model in Belgium: a single centre, randomised, double-blind phase 2 study 3 days ago
- Dual N-linked glycosylation at residues 133 and 158 in the hemagglutinin are essential for the efficacy of H7N9 avian influenza virus like particle vaccine in chickens and mice 3 days ago
[Go Top] [Close Window]