PMID- 28874549 OWN - NLM STAT- MEDLINE DCOM- 20180618 LR - 20181113 IS - 1091-6490 (Electronic) IS - 0027-8424 (Print) IS - 0027-8424 (Linking) VI - 114 IP - 42 DP - 2017 Oct 17 TI - Molecular basis of mammalian transmissibility of avian H1N1 influenza viruses and their pandemic potential. PG - 11217-11222 LID - 10.1073/pnas.1713974114 [doi] AB - North American wild birds are an important reservoir of influenza A viruses, yet the potential of viruses in this reservoir to transmit and cause disease in mammals is not well understood. Our surveillance of avian influenza viruses (AIVs) at Delaware Bay, USA, revealed a group of similar H1N1 AIVs isolated in 2009, some of which were airborne-transmissible in the ferret model without prior adaptation. Comparison of the genomes of these viruses revealed genetic markers of airborne transmissibility in the Polymerase Basic 2 (PB2), PB1, PB1-F2, Polymerase Acidic-X (PA-X), Nonstructural Protein 1 (NS1), and Nuclear Export Protein (NEP) genes. We studied the role of NS1 in airborne transmission and found that NS1 mutants that were not airborne-transmissible caused limited tissue pathology in the upper respiratory tract (URT). Viral maturation was also delayed, evident as strong intranuclear staining and little virus at the mucosa. Our study of this naturally occurring constellation of genetic markers has provided insights into the poorly understood phenomenon of AIV airborne transmissibility by revealing a role for NS1 and characteristics of viral replication in the URT that were associated with airborne transmission. The transmissibility of these viruses further highlights the pandemic potential of AIVs in the wild bird reservoir and the need to maintain surveillance. FAU - Zanin, Mark AU - Zanin M AD - Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105. FAU - Wong, Sook-San AU - Wong SS AD - Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105. FAU - Barman, Subrata AU - Barman S AD - Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105. FAU - Kaewborisuth, Challika AU - Kaewborisuth C AD - Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105. FAU - Vogel, Peter AU - Vogel P AD - Veterinary Pathology Core, St. Jude Children's Research Hospital, Memphis, TN 38105. FAU - Rubrum, Adam AU - Rubrum A AD - Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105. FAU - Darnell, Daniel AU - Darnell D AD - Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105. FAU - Marinova-Petkova, Atanaska AU - Marinova-Petkova A AD - Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105. FAU - Krauss, Scott AU - Krauss S AD - Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105. FAU - Webby, Richard J AU - Webby RJ AD - Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105. FAU - Webster, Robert G AU - Webster RG AD - Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105; robert.webster@stjude.org. LA - eng GR - HHSN266200700005C/AI/NIAID NIH HHS/United States GR - HHSN272201400006C/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20170905 PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 SB - IM CIN - Proc Natl Acad Sci U S A. 2017 Oct 17;114(42):11012-11014. PMID: 29073013 MH - Animals MH - Charadriiformes/*virology MH - Chick Embryo MH - Disease Vectors MH - Ferrets MH - Influenza A Virus, H1N1 Subtype/genetics/*pathogenicity MH - Male MH - Orthomyxoviridae Infections/*transmission MH - Respiratory System/virology MH - Virus Replication PMC - PMC5651783 OTO - NOTNLM OT - H1N1 OT - airborne transmission OT - avian influenza virus OT - ferret OT - nonstructural protein 1 COIS- The authors declare no conflict of interest. EDAT- 2017/09/07 06:00 MHDA- 2018/06/19 06:00 PMCR- 2018/04/17 CRDT- 2017/09/07 06:00 PHST- 2017/09/07 06:00 [pubmed] PHST- 2018/06/19 06:00 [medline] PHST- 2017/09/07 06:00 [entrez] PHST- 2018/04/17 00:00 [pmc-release] AID - 1713974114 [pii] AID - 201713974 [pii] AID - 10.1073/pnas.1713974114 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 2017 Oct 17;114(42):11217-11222. doi: 10.1073/pnas.1713974114. Epub 2017 Sep 5.