Shortening the unstructured, interdomain region of the non-structural protein NS1 of an avian H1N1 influenza virus increases its replication and pathogenicity in chickens.
Currently circulating H5N1 influenza viruses have undergone a complex evolution since the appearance of their progenitor A/Goose/Guangdong/1/96 in 1996. After the eradication of the H5N1 viruses that emerged in Hong Kong in 1997 (HK/97 viruses), new genotypes of H5N1 viruses emerged in the same region in 2000 that were more pathogenic for both chickens and mice than HK/97 viruses. These, as well as virtually all highly pathogenic H5N1 viruses since 2000, harbour a deletion of aa 80-84 in the unstructured region of the non-structural (NS) protein NS1 linking its RNA-binding domain to its effector domain. NS segments harbouring this mutation have since been found in non-H5N1 viruses and we asked whether this 5 aa deletion could have a general effect not limited to the NS1 of H5N1 viruses. We genetically engineered this deletion in the NS segment of a duck-origin avian H1N1 virus, and compared the in vivo and in vitro properties of the WT and NSdel8084 viruses. In experimentally infected chickens, the NSdel8084 virus showed both an increased replication potential and an increased pathogenicity. This in vivo phenotype was correlated with a higher replicative efficiency in vitro, both in embryonated eggs and in a chicken lung epithelial cell line. Our data demonstrated that the increased replicative potential conferred by this small deletion was a general feature not restricted to NS1 from H5N1 viruses and suggested that viruses acquiring this mutation may be selected positively in the future.
UMR1282 Infectiologie et Santé Publique, Université François Rabelais de Tours, 37000 Tours, France.|Equipe PIA, UMR1282 Infectiologie et Santé Publique, INRA, 37380 Nouzilly, France.
Sascha
S
Trapp
Equipe BioVA, UMR1282 Infectiologie et Santé Publique, Institut National de la Recherche Agronomique, 37380 Nouzilly, France.|UMR1282 Infectiologie et Santé Publique, Université François Rabelais de Tours, 37000 Tours, France.|Equipe PIA, UMR1282 Infectiologie et Santé Publique, INRA, 37380 Nouzilly, France.
Denis
D
Soubieux
UMR1282 Infectiologie et Santé Publique, Université François Rabelais de Tours, 37000 Tours, France.|Equipe PIA, UMR1282 Infectiologie et Santé Publique, INRA, 37380 Nouzilly, France.
Hélène
H
Marty
UMR1282 Infectiologie et Santé Publique, Université François Rabelais de Tours, 37000 Tours, France.|Equipe PIA, UMR1282 Infectiologie et Santé Publique, INRA, 37380 Nouzilly, France.
Evelyne
E
Esnault
Equipe BioVA, UMR1282 Infectiologie et Santé Publique, Institut National de la Recherche Agronomique, 37380 Nouzilly, France.|UMR1282 Infectiologie et Santé Publique, Université François Rabelais de Tours, 37000 Tours, France.
Thomas W
TW
Hoffmann
Equipe BioVA, UMR1282 Infectiologie et Santé Publique, Institut National de la Recherche Agronomique, 37380 Nouzilly, France.|UMR1282 Infectiologie et Santé Publique, Université François Rabelais de Tours, 37000 Tours, France.
Margaux
M
Chandenier
UMR1282 Infectiologie et Santé Publique, Université François Rabelais de Tours, 37000 Tours, France.|Equipe PIA, UMR1282 Infectiologie et Santé Publique, INRA, 37380 Nouzilly, France.
Adrien
A
Lion
UMR1282 Infectiologie et Santé Publique, Université François Rabelais de Tours, 37000 Tours, France.|Equipe PIA, UMR1282 Infectiologie et Santé Publique, INRA, 37380 Nouzilly, France.
Emmanuel
E
Kut
UMR1282 Infectiologie et Santé Publique, Université François Rabelais de Tours, 37000 Tours, France.|Equipe PIA, UMR1282 Infectiologie et Santé Publique, INRA, 37380 Nouzilly, France.
Pascale
P
Quéré
LUNAM Université, École Nationale Vétérinaire, agro-alimentaire et de l'alimentation Nantes-Atlantique (Oniris), 44307 Nantes, France.|INRA UMR 703, APEX, Oniris-La Chantrerie, 44307 Nantes, France.
Thibaut
T
Larcher
LUNAM Université, École Nationale Vétérinaire, agro-alimentaire et de l'alimentation Nantes-Atlantique (Oniris), 44307 Nantes, France.|INRA UMR 703, APEX, Oniris-La Chantrerie, 44307 Nantes, France.
Mireille
M
Ledevin
Université Paris Diderot, Sorbonne Paris Cité, Unité de Génétique Moléculaire des Virus à ARN, EA302, 75015 Paris, France.|CNRS, UMR3569, 75015 Paris, France.|Institut Pasteur, Unité de Génétique Moléculaire des Virus à ARN, Département de Virologie, 75015 Paris, France.
Sandie
S
Munier
Université Paris Diderot, Sorbonne Paris Cité, Unité de Génétique Moléculaire des Virus à ARN, EA302, 75015 Paris, France.|CNRS, UMR3569, 75015 Paris, France.|Institut Pasteur, Unité de Génétique Moléculaire des Virus à ARN, Département de Virologie, 75015 Paris, France.
Nadia
N
Naffakh
Equipe BioVA, UMR1282 Infectiologie et Santé Publique, Institut National de la Recherche Agronomique, 37380 Nouzilly, France.|UMR1282 Infectiologie et Santé Publique, Université François Rabelais de Tours, 37000 Tours, France.|Equipe PIA, UMR1282 Infectiologie et Santé Publique, INRA, 37380 Nouzilly, France.
Daniel
D
Marc
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002642:Chick Embryo; D002645:Chickens; D016207:Cytokines / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D053124:Influenza A Virus, H5N1 Subtype / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D005585:Influenza in Birds / Q000276:immunology / Q000473:pathology / Q000821:virology; D007370:Interferon Type I / Q000096:biosynthesis; D008168:Lung / Q000473:pathology / Q000821:virology; D051379:Mice; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D013045:Species Specificity; D019562:Viral Load; D017361:Viral Nonstructural Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D014774:Virulence / Q000235:genetics / Q000502:physiology; D014779:Virus Replication / Q000235:genetics / Q000502:physiology
D016207:Cytokines; D004279:DNA, Viral; C085820:INS1 protein, influenza virus; D007370:Interferon Type I; D012333:RNA, Messenger; D017361:Viral Nonstructural Proteins