Giuseppe
Emeritus
Abstract. Minimal molecular constraints for respiratory droplet transmission of an avian?human H9N2 influenza A virus ? PNAS
Minimal molecular constraints for respiratory droplet transmission of an avian?human H9N2 influenza A virus
1. Erin M. Sorrell,1, 2. Hongquan Wan,1,2, 3. Yonas Araya, 4. Haichen Song,3 and 5. Daniel R. Perez,4
-Author Affiliations
1. Department of Veterinary Medicine, University of Maryland, College Park, and Virginia?Maryland Regional College of Veterinary Medicine, 8075 Greenmead Drive, College Park, MD 20742
1. Edited by Peter Palese, Mount Sinai School of Medicine, New York, NY, and approved March 17, 2009 2.
1E.M.S. and H.W. contributed equally to this work. (received for review January 27, 2009)
Abstract
Pandemic influenza requires interspecies transmission of an influenza virus with a novel hemagglutinin (HA) subtytpe that can adapt to its new host through either reassortment or point mutations and transmit by aerosolized respiratory droplets. Two previous pandemics of 1957 and 1968 resulted from the reassortment of low pathogenic avian viruses and human subtypes of that period; however, conditions leading to a pandemic virus are still poorly understood. Given the endemic situation of avian H9N2 influenza with human-like receptor specificity in Eurasia and its occasional transmission to humans and pigs, we wanted to determine whether an avian?human H9N2 reassortant could gain respiratory transmission in a mammalian animal model, the ferret. Here we show that following adaptation in the ferret, a reassortant virus carrying the surface proteins of an avian H9N2 in a human H3N2 backbone can transmit efficiently via respiratory droplets, creating a clinical infection similar to human influenza infections. Minimal changes at the protein level were found in this virus capable of respiratory droplet transmission. A reassortant virus expressing only the HA and neuraminidase (NA) of the ferret-adapted virus was able to account for the transmissibility, suggesting that currently circulating avian H9N2 viruses require little adaptation in mammals following acquisition of all human virus internal genes through reassortment. Hemagglutinin inhibition (HI) analysis showed changes in the antigenic profile of the virus, which carries profound implications for vaccine seed stock preparation against avian H9N2 influenza. This report illustrates that aerosolized respiratory transmission is not exclusive to current human H1, H2, and H3 influenza subtypes.
* aerosol * ferrets * contact * pandemic * preparedness
Footnotes
* 4To whom correspondence should be addressed. E-mail: dperez1@umd.edu
* Author contributions: D.R.P. designed research; E.M.S., H.W., Y.A., and H.S. performed research; E.M.S., H.W., H.S., and D.R.P. analyzed data; and E.M.S., H.W., and D.R.P. wrote the paper. * ↵2Present address: Molecular, Virology, and Vaccines Branch, Influenza Division, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333.
* ↵3Present address: Synbiotics Corporation, 8075 Greenmead Drive, College Park, MD 20742.
* The authors declare no conflict of interest.
* This article is a PNAS Direct Submission.
* Data deposition: The nucleotide sequences of the RCP10 virus, A/ferret/Maryland/P10-UMD/08 (H9N2), have been deposited at NCBI's GenBank (accession nos. CY036274?CY036281). * This article contains supporting information online at www.pnas.org/cgi/content/full/0900877106/DCSupplemental.
* Freely available online through the PNAS open access option.
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<cite cite="http://www.pnas.org/content/106/18/7565.short?rss=1">Minimal molecular constraints for respiratory droplet transmission of an avian?human H9N2 influenza A virus ? PNAS</cite>1. Erin M. Sorrell,1, 2. Hongquan Wan,1,2, 3. Yonas Araya, 4. Haichen Song,3 and 5. Daniel R. Perez,4
-Author Affiliations
1. Department of Veterinary Medicine, University of Maryland, College Park, and Virginia?Maryland Regional College of Veterinary Medicine, 8075 Greenmead Drive, College Park, MD 20742
1. Edited by Peter Palese, Mount Sinai School of Medicine, New York, NY, and approved March 17, 2009 2.
1E.M.S. and H.W. contributed equally to this work. (received for review January 27, 2009)
Abstract
Pandemic influenza requires interspecies transmission of an influenza virus with a novel hemagglutinin (HA) subtytpe that can adapt to its new host through either reassortment or point mutations and transmit by aerosolized respiratory droplets. Two previous pandemics of 1957 and 1968 resulted from the reassortment of low pathogenic avian viruses and human subtypes of that period; however, conditions leading to a pandemic virus are still poorly understood. Given the endemic situation of avian H9N2 influenza with human-like receptor specificity in Eurasia and its occasional transmission to humans and pigs, we wanted to determine whether an avian?human H9N2 reassortant could gain respiratory transmission in a mammalian animal model, the ferret. Here we show that following adaptation in the ferret, a reassortant virus carrying the surface proteins of an avian H9N2 in a human H3N2 backbone can transmit efficiently via respiratory droplets, creating a clinical infection similar to human influenza infections. Minimal changes at the protein level were found in this virus capable of respiratory droplet transmission. A reassortant virus expressing only the HA and neuraminidase (NA) of the ferret-adapted virus was able to account for the transmissibility, suggesting that currently circulating avian H9N2 viruses require little adaptation in mammals following acquisition of all human virus internal genes through reassortment. Hemagglutinin inhibition (HI) analysis showed changes in the antigenic profile of the virus, which carries profound implications for vaccine seed stock preparation against avian H9N2 influenza. This report illustrates that aerosolized respiratory transmission is not exclusive to current human H1, H2, and H3 influenza subtypes.
* aerosol * ferrets * contact * pandemic * preparedness
Footnotes
* 4To whom correspondence should be addressed. E-mail: dperez1@umd.edu
* Author contributions: D.R.P. designed research; E.M.S., H.W., Y.A., and H.S. performed research; E.M.S., H.W., H.S., and D.R.P. analyzed data; and E.M.S., H.W., and D.R.P. wrote the paper. * ↵2Present address: Molecular, Virology, and Vaccines Branch, Influenza Division, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333.
* ↵3Present address: Synbiotics Corporation, 8075 Greenmead Drive, College Park, MD 20742.
* The authors declare no conflict of interest.
* This article is a PNAS Direct Submission.
* Data deposition: The nucleotide sequences of the RCP10 virus, A/ferret/Maryland/P10-UMD/08 (H9N2), have been deposited at NCBI's GenBank (accession nos. CY036274?CY036281). * This article contains supporting information online at www.pnas.org/cgi/content/full/0900877106/DCSupplemental.
* Freely available online through the PNAS open access option.
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