tetano
Editor, Senior Moderator
J Infect Dis. (2012) doi: 10.1093/infdis/jis571 First published online: September 10, 2012
Presence of oseltamivir-resistant pandemic A/H1N1 minor variants before drug therapy with subsequent selection and transmission
Elodie Ghedin1,*,
Edward C. Holmes2,3,
Jay V. DePasse1,
Lady Tatiana Pinilla4,
Adam Fitch1,
Marie-Eve Hamelin4,
Jesse Papenburg5 and
Guy Boivin4,*
+ Author Affiliations
1Department of Computational & Systems Biology, Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
2Center for Infectious Disease Dynamics, Department of Biology, The Pennsylvania State University, University Park, PA 16802, USA
3Fogarty International Center, National Institutes of Health, Bethesda, MD 20892, USA
4Centre de Recherche du Centre Hospitalier Universitaire de Qu?bec and Universit? Laval, Qu?bec City, Qu?bec, Canada
5McGill University Health Centre, Montr?al, Qu?bec, Canada
↵*Corresponding authors: Dr. Elodie Ghedin, Center for Vaccine Research, University of Pittsburgh School of Medicine, 3501 5th Avenue, BST3 Room 9043b, Pittsburgh, PA 15261. Phone: (412) 383-5850. E-mail: elg21@pitt.edu. Dr. Guy Boivin, Centre de Recherche en Infectiologie, CHUL, room RC-709, 2705 Laurier, Qu?bec City, QC, Canada. E-mail: guy.boivin@crchul.ulaval.ca
Abstract
A small proportion (1-1.5%) of 2009 pandemic A/H1N1 influenza viruses (A(H1N1)pdm09) are oseltamivir-resistant, due almost exclusively to a H275Y mutation in the neuraminidase protein. However, many individuals infected with resistant strains had not received antivirals. Whether drug-resistant viruses are initially present as minor variants in untreated subjects before they emerge as the dominant strain in a virus population is of great importance for predicting the speed at which resistance will arise. To address this issue, we employed ultra-deep sequencing of viral populations from serial nasopharyngeal specimens from an immunocompromised child and from two individuals in a household outbreak. We observed that the Y275 mutation was present as a minor variant in infected hosts prior to onset of therapy. We also found evidence for the transmission of this drug-resistant variant alongside drug-sensitive viruses. These observations provide important information on the relative fitness of the Y275 mutation in the absence of oseltamivir.
http://jid.oxfordjournals.org/content/early/2012/09/07/infdis.jis571.short?rss=1
Presence of oseltamivir-resistant pandemic A/H1N1 minor variants before drug therapy with subsequent selection and transmission
Elodie Ghedin1,*,
Edward C. Holmes2,3,
Jay V. DePasse1,
Lady Tatiana Pinilla4,
Adam Fitch1,
Marie-Eve Hamelin4,
Jesse Papenburg5 and
Guy Boivin4,*
+ Author Affiliations
1Department of Computational & Systems Biology, Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
2Center for Infectious Disease Dynamics, Department of Biology, The Pennsylvania State University, University Park, PA 16802, USA
3Fogarty International Center, National Institutes of Health, Bethesda, MD 20892, USA
4Centre de Recherche du Centre Hospitalier Universitaire de Qu?bec and Universit? Laval, Qu?bec City, Qu?bec, Canada
5McGill University Health Centre, Montr?al, Qu?bec, Canada
↵*Corresponding authors: Dr. Elodie Ghedin, Center for Vaccine Research, University of Pittsburgh School of Medicine, 3501 5th Avenue, BST3 Room 9043b, Pittsburgh, PA 15261. Phone: (412) 383-5850. E-mail: elg21@pitt.edu. Dr. Guy Boivin, Centre de Recherche en Infectiologie, CHUL, room RC-709, 2705 Laurier, Qu?bec City, QC, Canada. E-mail: guy.boivin@crchul.ulaval.ca
Abstract
A small proportion (1-1.5%) of 2009 pandemic A/H1N1 influenza viruses (A(H1N1)pdm09) are oseltamivir-resistant, due almost exclusively to a H275Y mutation in the neuraminidase protein. However, many individuals infected with resistant strains had not received antivirals. Whether drug-resistant viruses are initially present as minor variants in untreated subjects before they emerge as the dominant strain in a virus population is of great importance for predicting the speed at which resistance will arise. To address this issue, we employed ultra-deep sequencing of viral populations from serial nasopharyngeal specimens from an immunocompromised child and from two individuals in a household outbreak. We observed that the Y275 mutation was present as a minor variant in infected hosts prior to onset of therapy. We also found evidence for the transmission of this drug-resistant variant alongside drug-sensitive viruses. These observations provide important information on the relative fitness of the Y275 mutation in the absence of oseltamivir.
http://jid.oxfordjournals.org/content/early/2012/09/07/infdis.jis571.short?rss=1