Giuseppe
Emeritus
Does Pandemic A/H1N1 Virus Have the Potential To Become More Pathogenic? (mBio, abstract, edited)
[Source: mBio, full text: <cite cite="http://mbio.asm.org/content/1/5/e00249-10.short?rss=1">Does Pandemic A/H1N1 Virus Have the Potential To Become More Pathogenic? ? mBio</cite>. Abstract, edited.]
Does Pandemic A/H1N1 Virus Have the Potential To Become More Pathogenic?
1. Natalia A. Ilyushina a,b*, 2. Mariette F. Ducatez a, 3. Jerold E. Rehg c, 4. Bindumadhav M. Marathe a, 5. Henju Marjuki a, 6. Nicolai V. Bovin d, 7. Robert G. Webster a, and 8. Richard J. Webby a
Author Affiliations
1. Department of Infectious Diseases, St. Jude Children?s Research Hospital, Memphis, Tennessee, USA(a);
2. The D.I. Ivanovsky Institute of Virology RAMS, Moscow, Russia(b);
3. Department of Pathology, St. Jude Children?s Research Hospital, Memphis, Tennessee, USA(c); and
4. Shemyakin Institute of Bioorganic Chemistry, Moscow, Russia(d)
1. Address correspondence to Richard J. Webby, richard.webby@stjude.org.
* Present address: Department of Pediatrics, Dartmouth Medical School, Lebanon, New Hampshire, USA.
1. N.A.I. and M.F.D. contributed equally to this work.
2. Editor W. Ian Lipkin, Columbia University
ABSTRACT
Epidemiologic observations that have been made in the context of the current pandemic influenza virus include a stable virulence phenotype and a lack of propensity to reassort with seasonal strains. In an attempt to determine whether either of these observations could change in the future, we coinfected differentiated human airway cells with seasonal oseltamivir-resistant A/New Jersey/15/07 and pandemic A/Tennessee/1-560/09 (H1N1) viruses in three ratios (10:90, 50:50, and 90:10) and examined the resulting progeny viruses after 10 sequential passages. When the pandemic virus was initially present at multiplicities of infection equal to or greater than those for the seasonal virus, only pandemic virus genotypes were detected. These adapted pandemic strains did, however, contain two nonsynonymous mutations (hemagglutinin K154Q and polymerase acidic protein L295P) that conferred a more virulent phenotype, both in cell cultures and in ferrets, than their parental strains. The polymerase acidic protein mutation increased polymerase activity at 37?C, and the hemagglutinin change affected binding of the virus to α2,6-sialyl receptors. When the seasonal A/H1N1 virus was initially present in excess, the dominant progeny virus was a reassortant containing the hemagglutinin gene from the seasonal strain and the remaining genes from the pandemic virus. Our study demonstrates that the emergence of an A/H1N1 pandemic strain of higher virulence is possible and that, despite their lack of detection thus far in humans, viable seasonal/pandemic virus reassortants can be generated.
IMPORTANCE
This report supplies a key piece of information for investigating future evolution scenarios of pandemic A/H1N1 influenza in the human population. We report that the emergence of an A/H1N1 pandemic strain of higher virulence is possible and that, despite their lack of detection thus far in humans, viable seasonal/pandemic virus reassortants can be generated.
Footnotes
* Citation Ilyushina, N. A., M. F. Ducatez, J. E. Rehg, B. M. Marathe, H. Marjuki, et al. 2010. Does pandemic A/H1N1 virus have the potential to become more pathogenic? mBio 1(5):e00249-10. doi:10.1128/mBio.00249-10.
* Received 24 September 2010
* Accepted 18 October 2010
* Published 16 November 2010
* Copyright ? 2010 Ilyushina et al.
This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported License, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited.
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[Source: mBio, full text: <cite cite="http://mbio.asm.org/content/1/5/e00249-10.short?rss=1">Does Pandemic A/H1N1 Virus Have the Potential To Become More Pathogenic? ? mBio</cite>. Abstract, edited.]
Does Pandemic A/H1N1 Virus Have the Potential To Become More Pathogenic?
1. Natalia A. Ilyushina a,b*, 2. Mariette F. Ducatez a, 3. Jerold E. Rehg c, 4. Bindumadhav M. Marathe a, 5. Henju Marjuki a, 6. Nicolai V. Bovin d, 7. Robert G. Webster a, and 8. Richard J. Webby a
Author Affiliations
1. Department of Infectious Diseases, St. Jude Children?s Research Hospital, Memphis, Tennessee, USA(a);
2. The D.I. Ivanovsky Institute of Virology RAMS, Moscow, Russia(b);
3. Department of Pathology, St. Jude Children?s Research Hospital, Memphis, Tennessee, USA(c); and
4. Shemyakin Institute of Bioorganic Chemistry, Moscow, Russia(d)
1. Address correspondence to Richard J. Webby, richard.webby@stjude.org.
* Present address: Department of Pediatrics, Dartmouth Medical School, Lebanon, New Hampshire, USA.
1. N.A.I. and M.F.D. contributed equally to this work.
2. Editor W. Ian Lipkin, Columbia University
ABSTRACT
Epidemiologic observations that have been made in the context of the current pandemic influenza virus include a stable virulence phenotype and a lack of propensity to reassort with seasonal strains. In an attempt to determine whether either of these observations could change in the future, we coinfected differentiated human airway cells with seasonal oseltamivir-resistant A/New Jersey/15/07 and pandemic A/Tennessee/1-560/09 (H1N1) viruses in three ratios (10:90, 50:50, and 90:10) and examined the resulting progeny viruses after 10 sequential passages. When the pandemic virus was initially present at multiplicities of infection equal to or greater than those for the seasonal virus, only pandemic virus genotypes were detected. These adapted pandemic strains did, however, contain two nonsynonymous mutations (hemagglutinin K154Q and polymerase acidic protein L295P) that conferred a more virulent phenotype, both in cell cultures and in ferrets, than their parental strains. The polymerase acidic protein mutation increased polymerase activity at 37?C, and the hemagglutinin change affected binding of the virus to α2,6-sialyl receptors. When the seasonal A/H1N1 virus was initially present in excess, the dominant progeny virus was a reassortant containing the hemagglutinin gene from the seasonal strain and the remaining genes from the pandemic virus. Our study demonstrates that the emergence of an A/H1N1 pandemic strain of higher virulence is possible and that, despite their lack of detection thus far in humans, viable seasonal/pandemic virus reassortants can be generated.
IMPORTANCE
This report supplies a key piece of information for investigating future evolution scenarios of pandemic A/H1N1 influenza in the human population. We report that the emergence of an A/H1N1 pandemic strain of higher virulence is possible and that, despite their lack of detection thus far in humans, viable seasonal/pandemic virus reassortants can be generated.
Footnotes
* Citation Ilyushina, N. A., M. F. Ducatez, J. E. Rehg, B. M. Marathe, H. Marjuki, et al. 2010. Does pandemic A/H1N1 virus have the potential to become more pathogenic? mBio 1(5):e00249-10. doi:10.1128/mBio.00249-10.
* Received 24 September 2010
* Accepted 18 October 2010
* Published 16 November 2010
* Copyright ? 2010 Ilyushina et al.
This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported License, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited.
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