tetano
Editor, Senior Moderator
J Clin Microbiol. 2011 May 4. [Epub ahead of print]
Ultra-sensitive detection of drug resistant pandemic 2009 (H1N1) influenza A virus by Rare-Variant-Sensitive High Resolution Melting.
Chen N, Pinsky BA, Lee BP, Lin M, Schrijver I.
Source
Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Abstract
Oseltamivir (Tamiflu), an oral neuraminidase inhibitor, has been widely used to treat pandemic 2009 (H1N1) influenza A. Though a majority of 2009 (H1N1) influenza A remains oseltamivir-susceptible, the threat of resistance due to the His275Tyr mutation, is highlighted by the limitations of alternative therapies and the potential for rapid, global fixation of this mutation in the circulating influenza A population. In order to better understand the emergence of resistance, we developed a Rare-Variant-Sensitive High Resolution Melting (RVS-HRM) method that is able to detect the His275Tyr oseltamivir resistance mutation to 0.5% in a background of susceptible virus. We applied RVS-HRM to clinical specimens from patients who developed oseltamivir resistance and demonstrated the ultra-sensitive detection of influenza A N1 neuraminidase quasispecies. Interestingly, we were unable to detect the oseltamivir resistance mutation in pre-treatment samples, suggesting that resistant virus does not reach even this very low detection threshold until exposed to selective drug pressure. Thus, patients na?ve to oseltamivir are most likely to be susceptible when this drug is used as a first-line treatment modality.
PMID:
21543559
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/21543559
Ultra-sensitive detection of drug resistant pandemic 2009 (H1N1) influenza A virus by Rare-Variant-Sensitive High Resolution Melting.
Chen N, Pinsky BA, Lee BP, Lin M, Schrijver I.
Source
Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Abstract
Oseltamivir (Tamiflu), an oral neuraminidase inhibitor, has been widely used to treat pandemic 2009 (H1N1) influenza A. Though a majority of 2009 (H1N1) influenza A remains oseltamivir-susceptible, the threat of resistance due to the His275Tyr mutation, is highlighted by the limitations of alternative therapies and the potential for rapid, global fixation of this mutation in the circulating influenza A population. In order to better understand the emergence of resistance, we developed a Rare-Variant-Sensitive High Resolution Melting (RVS-HRM) method that is able to detect the His275Tyr oseltamivir resistance mutation to 0.5% in a background of susceptible virus. We applied RVS-HRM to clinical specimens from patients who developed oseltamivir resistance and demonstrated the ultra-sensitive detection of influenza A N1 neuraminidase quasispecies. Interestingly, we were unable to detect the oseltamivir resistance mutation in pre-treatment samples, suggesting that resistant virus does not reach even this very low detection threshold until exposed to selective drug pressure. Thus, patients na?ve to oseltamivir are most likely to be susceptible when this drug is used as a first-line treatment modality.
PMID:
21543559
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/21543559