tetano
Editor, Senior Moderator
Published ahead of print 20 November 2013, doi: 10.1128/JVI.02044-13 JVI.02044-13
Emergence of the Virulence-associated PB2 E627K Substitution in a Fatal Human Case of Highly Pathogenic Avian Influenza Virus A(H7N7) Infection Determined by Illumina Ultra-deep Sequencing
Marcel Jonges1,2#,
Matthijs R.A. Welkers3,
Rienk E. Jeeninga3,
Adam Meijer1,
Peter Schneeberger4,
Ron A.M. Fouchier2,
Menno D. de Jong3 and
Marion Koopmans1,2
+ Author Affiliations
Department of Virology, Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands1
Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands2
Department of Medical Microbiology, Academic Medical Center, Amsterdam, The Netherlands3
Department of Medical Microbiology and Infection Control, Jeroen Bosch Hospital, 's-Hertogenbosch, The Netherlands4
ABSTRACT
Avian influenza viruses are capable of crossing the species barrier and infect humans. Although evidence of human-to-human transmission of avian influenza viruses to date is limited, evolution of variants towards more efficient human-to-human transmission could result in a new influenza virus pandemic. In both the avian influenza A(H5N1) and the recently emerging avian influenza A(H7N9) viruses, the PB2 E627K mutation appears of key importance for human adaptation. During a large influenza A(H7N7) outbreak in the Netherlands in 2003, the A(H7N7) virus isolated from a fatal human case contained the PB2 E627K mutation as well as a HA K416R mutation. In this study, we aimed to investigate whether these mutations occurred in the avian or the human host by Illumina ultra-deep sequencing of three previously uninvestigated clinical samples obtained from the fatal case. In addition, we investigated three chicken samples, two of which were obtained from the source farm. Results showed that the PB2 E627K mutation was not present in any of the chicken samples tested. Surprisingly, the avian samples were characterized by the presence of influenza defective RNA segments, suggestive for the synthesis of defective-interfering viruses during infection in poultry. In the human samples, the PB2 E627K mutation was identified with increasing frequency during infection. Our results strongly suggest that human adaptation marker PB2 E627K has emerged during virus infection of a single human host, emphasizing the importance of reducing human exposure to avian influenza viruses to reduce the likelihood of viral adaptation to humans.
http://jvi.asm.org/content/early/2013/11/15/JVI.02044-13.abstract
Emergence of the Virulence-associated PB2 E627K Substitution in a Fatal Human Case of Highly Pathogenic Avian Influenza Virus A(H7N7) Infection Determined by Illumina Ultra-deep Sequencing
Marcel Jonges1,2#,
Matthijs R.A. Welkers3,
Rienk E. Jeeninga3,
Adam Meijer1,
Peter Schneeberger4,
Ron A.M. Fouchier2,
Menno D. de Jong3 and
Marion Koopmans1,2
+ Author Affiliations
Department of Virology, Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands1
Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands2
Department of Medical Microbiology, Academic Medical Center, Amsterdam, The Netherlands3
Department of Medical Microbiology and Infection Control, Jeroen Bosch Hospital, 's-Hertogenbosch, The Netherlands4
ABSTRACT
Avian influenza viruses are capable of crossing the species barrier and infect humans. Although evidence of human-to-human transmission of avian influenza viruses to date is limited, evolution of variants towards more efficient human-to-human transmission could result in a new influenza virus pandemic. In both the avian influenza A(H5N1) and the recently emerging avian influenza A(H7N9) viruses, the PB2 E627K mutation appears of key importance for human adaptation. During a large influenza A(H7N7) outbreak in the Netherlands in 2003, the A(H7N7) virus isolated from a fatal human case contained the PB2 E627K mutation as well as a HA K416R mutation. In this study, we aimed to investigate whether these mutations occurred in the avian or the human host by Illumina ultra-deep sequencing of three previously uninvestigated clinical samples obtained from the fatal case. In addition, we investigated three chicken samples, two of which were obtained from the source farm. Results showed that the PB2 E627K mutation was not present in any of the chicken samples tested. Surprisingly, the avian samples were characterized by the presence of influenza defective RNA segments, suggestive for the synthesis of defective-interfering viruses during infection in poultry. In the human samples, the PB2 E627K mutation was identified with increasing frequency during infection. Our results strongly suggest that human adaptation marker PB2 E627K has emerged during virus infection of a single human host, emphasizing the importance of reducing human exposure to avian influenza viruses to reduce the likelihood of viral adaptation to humans.
http://jvi.asm.org/content/early/2013/11/15/JVI.02044-13.abstract