Giuseppe
Emeritus
Variations in the Hemagglutinin of the 2009 H1N1 Pandemic Virus: Potential for Strains with Altered Virulence Phenotype? (PLoS, abstract, edited)
[Source: PLoS Pathogens, full text: <cite cite="http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1001145?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+plospathogens%2FNewArticles+%28Ambra+-+Pathogens+New+Articles%29">PLoS Pathogens: Variations in the Hemagglutinin of the 2009 H1N1 Pandemic Virus: Potential for Strains with Altered Virulence Phenotype?</cite>. Abstract, edited.]
Variations in the Hemagglutinin of the 2009 H1N1 Pandemic Virus: Potential for Strains with Altered Virulence Phenotype?
Jianqiang Ye 1,2, Erin M. Sorrell 1,2, Yibin Cai 1,2, Hongxia Shao 1,2, Kemin Xu 1,2, Lindomar Pena 1,2, Danielle Hickman 1,2, Haichen Song 3, Matthew Angel 1,2, Rafael A. Medina 4,5,6, Balaji Manicassamy 4,5,6, Adolfo Garcia-Sastre 4,5,6, Daniel R. Perez 1,2*
1 Virginia-Maryland Regional College of Veterinary Medicine, College Park, Maryland, United States of America,
2 Department of Veterinary Medicine, University of Maryland, College Park, Maryland, United States of America,
3 Synbiotics Corporation, College Park, Maryland, United States of America,
4 Department of Microbiology, Mount Sinai School of Medicine, New York, New York, United States of America,
5 Institute of Global Health and Emerging Pathogens, Mount Sinai School of Medicine, New York, New York, United States of America,
6 Department of Medicine, Division of Infectious Diseases, Mount Sinai School of Medicine, New York, New York, United States of America
Abstract
A novel, swine-origin influenza H1N1 virus (H1N1pdm) caused the first pandemic of the 21st century. This pandemic, although efficient in transmission, is mild in virulence. This atypical mild pandemic season has raised concerns regarding the potential of this virus to acquire additional virulence markers either through further adaptation or possibly by immune pressure in the human host. Using the mouse model we generated, within a single round of infection with A/California /04/09/H1N1 (Ca/04), a virus lethal in mice?herein referred to as mouse-adapted Ca/04 (ma-Ca/04). Five amino acid substitutions were found in the genome of ma-Ca/04: 3 in HA (D131E, S186P and A198E), 1 in PA (E298K) and 1 in NP (D101G). Reverse genetics analyses of these mutations indicate that all five mutations from ma-Ca/04 contributed to the lethal phenotype; however, the D131E and S186P mutations?which are also found in the 1918 and seasonal H1N1 viruses?in HA alone were sufficient to confer virulence of Ca/04 in mice. HI assays against H1N1pdm demonstrate that the D131E and S186P mutations caused minor antigenic changes and, likely, affected receptor binding. The rapid selection of ma-Ca/04 in mice suggests that a virus containing this constellation of amino acids might have already been present in Ca/04, likely as minor quasispecies.
Author Summary
The 19th century experienced three major influenza pandemics: the Spanish flu of 1918 (H1N1), the Asian flu of 1957 (H2N2) and the Hong Kong flu of 1968 (H3N2). These pandemics were introduced into the human population through the accumulation of avian and human influenza genes (genetic reassortment), creating with each pandemic a novel influenza virus, one that the human population had not been exposed to. These pandemics were associated with high morbidity and mortality; the 1918 pandemic was responsible for an estimated 40 million deaths. In April 2009, a novel, swine-origin influenza H1N1 virus (H1N1pdm) caused the first influenza pandemic of the 21st century. This pandemic was a result of genetic reassortment between not only human and avian influenza genes, but also swine influenza genes. This H1N1 pandemic, although efficient in human-to-human transmission, differed greatly from the previous pandemics in its mild virulence. This atypical mild pandemic season has raised concerns regarding the potential of this virus to become more virulent. Using a mouse model, we were able to demonstrate that this pandemic strain is amenable to mutations that lead to a more virulent virus.
Citation: Ye J, Sorrell EM, Cai Y, Shao H, Xu K, et al. (2010) Variations in the Hemagglutinin of the 2009 H1N1 Pandemic Virus: Potential for Strains with Altered Virulence Phenotype? PLoS Pathog 6(10): e1001145. doi:10.1371/journal.ppat.1001145
Editor: Raul Andino, University of California San Francisco, United States of America
Received: March 5, 2010; Accepted: September 9, 2010; Published: October 14, 2010
Copyright: ? 2010 Ye et al.
This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This research was possible through funding by the CDC-HHS grant (1U01CI000355), NIAID-NIH grant, (R01AI052155), CSREES-USDA grant (1865-05523), and NIAID-NIH contract (HHSN266186700010C). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
* E-mail: dperez1@umd.edu
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[Source: PLoS Pathogens, full text: <cite cite="http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1001145?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+plospathogens%2FNewArticles+%28Ambra+-+Pathogens+New+Articles%29">PLoS Pathogens: Variations in the Hemagglutinin of the 2009 H1N1 Pandemic Virus: Potential for Strains with Altered Virulence Phenotype?</cite>. Abstract, edited.]
Variations in the Hemagglutinin of the 2009 H1N1 Pandemic Virus: Potential for Strains with Altered Virulence Phenotype?
Jianqiang Ye 1,2, Erin M. Sorrell 1,2, Yibin Cai 1,2, Hongxia Shao 1,2, Kemin Xu 1,2, Lindomar Pena 1,2, Danielle Hickman 1,2, Haichen Song 3, Matthew Angel 1,2, Rafael A. Medina 4,5,6, Balaji Manicassamy 4,5,6, Adolfo Garcia-Sastre 4,5,6, Daniel R. Perez 1,2*
1 Virginia-Maryland Regional College of Veterinary Medicine, College Park, Maryland, United States of America,
2 Department of Veterinary Medicine, University of Maryland, College Park, Maryland, United States of America,
3 Synbiotics Corporation, College Park, Maryland, United States of America,
4 Department of Microbiology, Mount Sinai School of Medicine, New York, New York, United States of America,
5 Institute of Global Health and Emerging Pathogens, Mount Sinai School of Medicine, New York, New York, United States of America,
6 Department of Medicine, Division of Infectious Diseases, Mount Sinai School of Medicine, New York, New York, United States of America
Abstract
A novel, swine-origin influenza H1N1 virus (H1N1pdm) caused the first pandemic of the 21st century. This pandemic, although efficient in transmission, is mild in virulence. This atypical mild pandemic season has raised concerns regarding the potential of this virus to acquire additional virulence markers either through further adaptation or possibly by immune pressure in the human host. Using the mouse model we generated, within a single round of infection with A/California /04/09/H1N1 (Ca/04), a virus lethal in mice?herein referred to as mouse-adapted Ca/04 (ma-Ca/04). Five amino acid substitutions were found in the genome of ma-Ca/04: 3 in HA (D131E, S186P and A198E), 1 in PA (E298K) and 1 in NP (D101G). Reverse genetics analyses of these mutations indicate that all five mutations from ma-Ca/04 contributed to the lethal phenotype; however, the D131E and S186P mutations?which are also found in the 1918 and seasonal H1N1 viruses?in HA alone were sufficient to confer virulence of Ca/04 in mice. HI assays against H1N1pdm demonstrate that the D131E and S186P mutations caused minor antigenic changes and, likely, affected receptor binding. The rapid selection of ma-Ca/04 in mice suggests that a virus containing this constellation of amino acids might have already been present in Ca/04, likely as minor quasispecies.
Author Summary
The 19th century experienced three major influenza pandemics: the Spanish flu of 1918 (H1N1), the Asian flu of 1957 (H2N2) and the Hong Kong flu of 1968 (H3N2). These pandemics were introduced into the human population through the accumulation of avian and human influenza genes (genetic reassortment), creating with each pandemic a novel influenza virus, one that the human population had not been exposed to. These pandemics were associated with high morbidity and mortality; the 1918 pandemic was responsible for an estimated 40 million deaths. In April 2009, a novel, swine-origin influenza H1N1 virus (H1N1pdm) caused the first influenza pandemic of the 21st century. This pandemic was a result of genetic reassortment between not only human and avian influenza genes, but also swine influenza genes. This H1N1 pandemic, although efficient in human-to-human transmission, differed greatly from the previous pandemics in its mild virulence. This atypical mild pandemic season has raised concerns regarding the potential of this virus to become more virulent. Using a mouse model, we were able to demonstrate that this pandemic strain is amenable to mutations that lead to a more virulent virus.
Citation: Ye J, Sorrell EM, Cai Y, Shao H, Xu K, et al. (2010) Variations in the Hemagglutinin of the 2009 H1N1 Pandemic Virus: Potential for Strains with Altered Virulence Phenotype? PLoS Pathog 6(10): e1001145. doi:10.1371/journal.ppat.1001145
Editor: Raul Andino, University of California San Francisco, United States of America
Received: March 5, 2010; Accepted: September 9, 2010; Published: October 14, 2010
Copyright: ? 2010 Ye et al.
This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This research was possible through funding by the CDC-HHS grant (1U01CI000355), NIAID-NIH grant, (R01AI052155), CSREES-USDA grant (1865-05523), and NIAID-NIH contract (HHSN266186700010C). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
* E-mail: dperez1@umd.edu
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