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Rapid quantitation of neuraminidase inhibitor drug resistance in influenza virus quasispecies.
Antivir Ther. 2008; 13(6):809-20.AT

Abstract

BACKGROUND

Emerging resistance of influenza viruses to neuraminidase inhibitors is a concern, both in surveillance of global circulating strains and in treatment of individual patients. Current methodologies to detect resistance rely on the use of cultured virus, thus taking time to complete or lacking the sensitivity to detect mutations in viral quasispecies. Methodology for rapid detection of clinically meaningful resistance is needed to assist individual patient management and to track the transmission of resistant viruses in the community.

METHODS

We have developed a pyrosequencing methodology to detect and quantitate influenza neuraminidase inhibitor resistance mutations in cultured virus and directly in clinical material. Our assays target polymorphisms associated with drug resistance in the neuraminidase genes of human influenza A H1N1 as well as human and avian H5N1 viruses. Quantitation can be achieved using viral RNA extracted directly from respiratory or tissue samples, thus eliminating the need for virus culture and allowing the assay of highly pathogenic viruses such as H5N1 without high containment laboratory facilities.

RESULTS

Antiviral-resistant quasispecies are detected and quantitated accurately when present in the total virus population at levels as low as 10%. Pyrosequencing is a real-time assay; therefore, results can be obtained within a clinically relevant timeframe and provide information capable of informing individual patient or outbreak management.

CONCLUSIONS

Pyrosequencing is ideally suited for early identification of emerging antiviral resistance in human and avian influenza infection and is a useful tool for laboratory surveillance and pandemic preparedness.

Authors+Show Affiliations

Health Protection Agency, Centre for Infection, London, UK. angie.lackenby@hpa.org.ukNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Validation Study

Language

eng

PubMed ID

18839782

Citation

Lackenby, Angie, et al. "Rapid Quantitation of Neuraminidase Inhibitor Drug Resistance in Influenza Virus Quasispecies." Antiviral Therapy, vol. 13, no. 6, 2008, pp. 809-20.
Lackenby A, Democratis J, Siqueira MM, et al. Rapid quantitation of neuraminidase inhibitor drug resistance in influenza virus quasispecies. Antivir Ther (Lond). 2008;13(6):809-20.
Lackenby, A., Democratis, J., Siqueira, M. M., & Zambon, M. C. (2008). Rapid quantitation of neuraminidase inhibitor drug resistance in influenza virus quasispecies. Antiviral Therapy, 13(6), 809-20.
Lackenby A, et al. Rapid Quantitation of Neuraminidase Inhibitor Drug Resistance in Influenza Virus Quasispecies. Antivir Ther (Lond). 2008;13(6):809-20. PubMed PMID: 18839782.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Rapid quantitation of neuraminidase inhibitor drug resistance in influenza virus quasispecies. AU - Lackenby,Angie, AU - Democratis,Jane, AU - Siqueira,Marilda M, AU - Zambon,Maria C, PY - 2008/10/9/pubmed PY - 2008/11/8/medline PY - 2008/10/9/entrez SP - 809 EP - 20 JF - Antiviral therapy JO - Antivir. Ther. (Lond.) VL - 13 IS - 6 N2 - BACKGROUND: Emerging resistance of influenza viruses to neuraminidase inhibitors is a concern, both in surveillance of global circulating strains and in treatment of individual patients. Current methodologies to detect resistance rely on the use of cultured virus, thus taking time to complete or lacking the sensitivity to detect mutations in viral quasispecies. Methodology for rapid detection of clinically meaningful resistance is needed to assist individual patient management and to track the transmission of resistant viruses in the community. METHODS: We have developed a pyrosequencing methodology to detect and quantitate influenza neuraminidase inhibitor resistance mutations in cultured virus and directly in clinical material. Our assays target polymorphisms associated with drug resistance in the neuraminidase genes of human influenza A H1N1 as well as human and avian H5N1 viruses. Quantitation can be achieved using viral RNA extracted directly from respiratory or tissue samples, thus eliminating the need for virus culture and allowing the assay of highly pathogenic viruses such as H5N1 without high containment laboratory facilities. RESULTS: Antiviral-resistant quasispecies are detected and quantitated accurately when present in the total virus population at levels as low as 10%. Pyrosequencing is a real-time assay; therefore, results can be obtained within a clinically relevant timeframe and provide information capable of informing individual patient or outbreak management. CONCLUSIONS: Pyrosequencing is ideally suited for early identification of emerging antiviral resistance in human and avian influenza infection and is a useful tool for laboratory surveillance and pandemic preparedness. SN - 1359-6535 UR - https://www.unboundmedicine.com/medline/citation/18839782/Rapid_quantitation_of_neuraminidase_inhibitor_drug_resistance_in_influenza_virus_quasispecies_ L2 - https://medlineplus.gov/birdflu.html DB - PRIME DP - Unbound Medicine ER -