Giuseppe
Emeritus
Antimicrob Agents Chemother. 2009 Dec 22. [Epub ahead of print]
Detection of molecular markers of drug resistance in the 2009 pandemic influenza A (H1N1) viruses using pyrosequencing.
Deyde VM, Sheu TG, Trujillo AA, Okomo-Adhiambo M, Garten R, Klimov AI, Gubareva LV. - Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta GA, 30333, USA.
Background:
M2 blockers, amantadine and rimantadine, and neuraminidase (NA) inhibitors (NAIs), oseltamivir and zanamivir, are FDA-approved for control of influenza A virus infections. The 2009 pandemic viruses (H1N1pdm) are reassortants that acquired M and NA gene segments from a Eurasian adamantane resistant swine virus. NAI-resistance in the H1N1pdm viruses has been rare and is mainly limited to oseltamivir exposed patients. The pyrosequencing assay has been proven a useful tool in surveillance for drug resistance in seasonal influenza A viruses.
Method:
Here we provide a protocol which allows detection of adamantane resistance markers as well as the I43T change- which is unique to the H1N1pdm M2 protein. The protocol also allows detection of changes at residues V116, I117, E119, Q136, K150, D151, D199, I223, H275, and N295 in the NA, known to alter NAI drug susceptibility.
Results:
We report here detection of the first cases of the oseltamivir resistance mutation H275Y and the change I223V in viruses from the US using the approach described in this study. Moreover, the assay permits a quick identification of the major NA group (V106/N248, I106/D248, or I106/N248) to which a pandemic virus belongs.
Conclusions:
pyrosequencing is well suited for detection of drug resistance markers and signature mutations in the M and NA of the pandemic H1N1 influenza viruses.
PMID: 20028826 [PubMed - as supplied by publisher]
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Detection of molecular markers of drug resistance in the 2009 pandemic influenza A (H1N1) viruses using pyrosequencing.
Deyde VM, Sheu TG, Trujillo AA, Okomo-Adhiambo M, Garten R, Klimov AI, Gubareva LV. - Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta GA, 30333, USA.
Background:
M2 blockers, amantadine and rimantadine, and neuraminidase (NA) inhibitors (NAIs), oseltamivir and zanamivir, are FDA-approved for control of influenza A virus infections. The 2009 pandemic viruses (H1N1pdm) are reassortants that acquired M and NA gene segments from a Eurasian adamantane resistant swine virus. NAI-resistance in the H1N1pdm viruses has been rare and is mainly limited to oseltamivir exposed patients. The pyrosequencing assay has been proven a useful tool in surveillance for drug resistance in seasonal influenza A viruses.
Method:
Here we provide a protocol which allows detection of adamantane resistance markers as well as the I43T change- which is unique to the H1N1pdm M2 protein. The protocol also allows detection of changes at residues V116, I117, E119, Q136, K150, D151, D199, I223, H275, and N295 in the NA, known to alter NAI drug susceptibility.
Results:
We report here detection of the first cases of the oseltamivir resistance mutation H275Y and the change I223V in viruses from the US using the approach described in this study. Moreover, the assay permits a quick identification of the major NA group (V106/N248, I106/D248, or I106/N248) to which a pandemic virus belongs.
Conclusions:
pyrosequencing is well suited for detection of drug resistance markers and signature mutations in the M and NA of the pandemic H1N1 influenza viruses.
PMID: 20028826 [PubMed - as supplied by publisher]
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