tetano
Editor, Senior Moderator
J Virol. 2012 Nov 14. [Epub ahead of print]
Systematic identification of H274Y compensatory mutations in influenza A virus neuraminidase by high-throughput screening.
Wu NC, Young AP, Dandekar S, Wijersuriya H, Al-Mawsawi LQ, Wu TT, Sun R.
Source
Department of Molecular and Medical Pharmacology, University of California, Los Angeles David Geffen School of Medicine, Los Angeles, CA 90095, USA.
Abstract
Compensatory mutations contribute to the appearance of the oseltamivir-resistance substitution H274Y in neuraminidase (NA) gene of H1N1 influenza viruses. Here, we describe a high-throughput screening method utilizing error-prone PCR and next generation sequencing to comprehensively screen NA for H274Y compensatory mutations. We found four mutations that can either fully (R194G, E214D) or partially (L250P, F239Y) compensate for the fitness deficiency of H274Y mutant. The compensatory effect of E214D is applicable in both the seasonal flu strain (A/New Caledonia/20/1999) and the 2009 pandemic swine flu (A/California/04/2009). The technique described here has the potential to profile a gene at the single nucleotide level to comprehend the dynamics of mutation space and fitness, and thus offers prediction power for emerging mutant species.
PMID:
23152521
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23152521
Systematic identification of H274Y compensatory mutations in influenza A virus neuraminidase by high-throughput screening.
Wu NC, Young AP, Dandekar S, Wijersuriya H, Al-Mawsawi LQ, Wu TT, Sun R.
Source
Department of Molecular and Medical Pharmacology, University of California, Los Angeles David Geffen School of Medicine, Los Angeles, CA 90095, USA.
Abstract
Compensatory mutations contribute to the appearance of the oseltamivir-resistance substitution H274Y in neuraminidase (NA) gene of H1N1 influenza viruses. Here, we describe a high-throughput screening method utilizing error-prone PCR and next generation sequencing to comprehensively screen NA for H274Y compensatory mutations. We found four mutations that can either fully (R194G, E214D) or partially (L250P, F239Y) compensate for the fitness deficiency of H274Y mutant. The compensatory effect of E214D is applicable in both the seasonal flu strain (A/New Caledonia/20/1999) and the 2009 pandemic swine flu (A/California/04/2009). The technique described here has the potential to profile a gene at the single nucleotide level to comprehend the dynamics of mutation space and fitness, and thus offers prediction power for emerging mutant species.
PMID:
23152521
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23152521