Giuseppe
Emeritus
[Source: Science, full text: (LINK). Abstract, edited.]
<CITE><ABBR>Science</ABBR> 22 June 2012: Vol. 336 no. 6088 pp. 1541-1547 - DOI: 10.1126/science.1222526 </CITE>
<CITE></CITE>
<CITE></CITE>Report The Potential for Respiratory Droplet?Transmissible A/H5N1 Influenza Virus to Evolve in a Mammalian Host
Colin A. Russell<SUP>1</SUP>,<SUP>2</SUP>,<SUP>3</SUP>, Judith M. Fonville<SUP>1</SUP>,<SUP>2</SUP>, Andr? E. X. Brown<SUP>4</SUP>, David F. Burke<SUP>1</SUP>,<SUP>2</SUP>, David L. Smith<SUP>3</SUP>,<SUP>5</SUP>,<SUP>6</SUP>, Sarah L. James<SUP>1</SUP>,<SUP>2</SUP>, Sander Herfst<SUP>7</SUP>, Sander van Boheemen<SUP>7</SUP>, Martin Linster<SUP>7</SUP>, Eefje J. Schrauwen<SUP>7</SUP>, Leah Katzelnick<SUP>1</SUP>,<SUP>2</SUP>, Ana Moster?n<SUP>1</SUP>,<SUP>2</SUP>,<SUP>8</SUP>, Thijs Kuiken<SUP>7</SUP>, Eileen Maher<SUP>9</SUP>, Gabriele Neumann<SUP>9</SUP>, Albert D. M. E. Osterhaus<SUP>7</SUP>, Yoshihiro Kawaoka<SUP>9</SUP>,<SUP>10</SUP>,<SUP>11</SUP>,<SUP>12</SUP>, Ron A. M. Fouchier<SUP>7</SUP>, Derek J. Smith<SUP>1</SUP>,<SUP>2</SUP>,<SUP>3</SUP>,<SUP>7</SUP>,*
Author Affiliations: <SUP>1</SUP>Department of Zoology, University of Cambridge, Cambridge CB2 3EJ, UK. <SUP>2</SUP>World Health Organization (WHO) Collaborating Center for Modeling, Evolution, and Control of Emerging Infectious Diseases, Cambridge CB2 3EJ, UK. <SUP>3</SUP>Fogarty International Center, National Institutes of Health, Bethesda, MD 20892, USA. <SUP>4</SUP>Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, UK. <SUP>5</SUP>Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA. <SUP>6</SUP>Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA. <SUP>7</SUP>Department of Virology, Erasmus Medical Center, Rotterdam 3015 CE, the Netherlands. <SUP>8</SUP>Center for Research in Health and Economics, Universitat Pompeu Fabra, Barcelona 08005, Spain. <SUP>9</SUP>Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706, USA. <SUP>10</SUP>Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. <SUP>11</SUP>Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. <SUP>12</SUP>Exploratory Research for Advanced Technology (ERATO) Infection-Induced Host Responses Project, Japan Science and Technology Agency, Saitama 102-0076, Japan.
*To whom correspondence should be addressed. E-mail: dsmith@zoo.cam.ac.uk
Abstract
Avian A/H5N1 influenza viruses pose a pandemic threat. As few as five amino acid substitutions, or four with reassortment, might be sufficient for mammal-to-mammal transmission through respiratory droplets. From surveillance data, we found that two of these substitutions are common in A/H5N1 viruses, and thus, some viruses might require only three additional substitutions to become transmissible via respiratory droplets between mammals. We used a mathematical model of within-host virus evolution to study factors that could increase and decrease the probability of the remaining substitutions evolving after the virus has infected a mammalian host. These factors, combined with the presence of some of these substitutions in circulating strains, make a virus evolving in nature a potentially serious threat. These results highlight critical areas in which more data are needed for assessing, and potentially averting, this threat.
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<CITE><ABBR>Science</ABBR> 22 June 2012: Vol. 336 no. 6088 pp. 1541-1547 - DOI: 10.1126/science.1222526 </CITE>
<CITE></CITE>
<CITE></CITE>Report The Potential for Respiratory Droplet?Transmissible A/H5N1 Influenza Virus to Evolve in a Mammalian Host
Colin A. Russell<SUP>1</SUP>,<SUP>2</SUP>,<SUP>3</SUP>, Judith M. Fonville<SUP>1</SUP>,<SUP>2</SUP>, Andr? E. X. Brown<SUP>4</SUP>, David F. Burke<SUP>1</SUP>,<SUP>2</SUP>, David L. Smith<SUP>3</SUP>,<SUP>5</SUP>,<SUP>6</SUP>, Sarah L. James<SUP>1</SUP>,<SUP>2</SUP>, Sander Herfst<SUP>7</SUP>, Sander van Boheemen<SUP>7</SUP>, Martin Linster<SUP>7</SUP>, Eefje J. Schrauwen<SUP>7</SUP>, Leah Katzelnick<SUP>1</SUP>,<SUP>2</SUP>, Ana Moster?n<SUP>1</SUP>,<SUP>2</SUP>,<SUP>8</SUP>, Thijs Kuiken<SUP>7</SUP>, Eileen Maher<SUP>9</SUP>, Gabriele Neumann<SUP>9</SUP>, Albert D. M. E. Osterhaus<SUP>7</SUP>, Yoshihiro Kawaoka<SUP>9</SUP>,<SUP>10</SUP>,<SUP>11</SUP>,<SUP>12</SUP>, Ron A. M. Fouchier<SUP>7</SUP>, Derek J. Smith<SUP>1</SUP>,<SUP>2</SUP>,<SUP>3</SUP>,<SUP>7</SUP>,*
Author Affiliations: <SUP>1</SUP>Department of Zoology, University of Cambridge, Cambridge CB2 3EJ, UK. <SUP>2</SUP>World Health Organization (WHO) Collaborating Center for Modeling, Evolution, and Control of Emerging Infectious Diseases, Cambridge CB2 3EJ, UK. <SUP>3</SUP>Fogarty International Center, National Institutes of Health, Bethesda, MD 20892, USA. <SUP>4</SUP>Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, UK. <SUP>5</SUP>Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA. <SUP>6</SUP>Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA. <SUP>7</SUP>Department of Virology, Erasmus Medical Center, Rotterdam 3015 CE, the Netherlands. <SUP>8</SUP>Center for Research in Health and Economics, Universitat Pompeu Fabra, Barcelona 08005, Spain. <SUP>9</SUP>Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706, USA. <SUP>10</SUP>Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. <SUP>11</SUP>Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. <SUP>12</SUP>Exploratory Research for Advanced Technology (ERATO) Infection-Induced Host Responses Project, Japan Science and Technology Agency, Saitama 102-0076, Japan.
*To whom correspondence should be addressed. E-mail: dsmith@zoo.cam.ac.uk
Abstract
Avian A/H5N1 influenza viruses pose a pandemic threat. As few as five amino acid substitutions, or four with reassortment, might be sufficient for mammal-to-mammal transmission through respiratory droplets. From surveillance data, we found that two of these substitutions are common in A/H5N1 viruses, and thus, some viruses might require only three additional substitutions to become transmissible via respiratory droplets between mammals. We used a mathematical model of within-host virus evolution to study factors that could increase and decrease the probability of the remaining substitutions evolving after the virus has infected a mammalian host. These factors, combined with the presence of some of these substitutions in circulating strains, make a virus evolving in nature a potentially serious threat. These results highlight critical areas in which more data are needed for assessing, and potentially averting, this threat.
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