title: Molecular genetic analysis of the Influenza A(H1N1)pdm09 virus from lethal and recovered cases in Russia from 2009 to 2014: Deletions in the nucleoprotein.
abstract: Influenza A(H1N1)pdm09 virus caused about 2000 laboratory confirmed lethal cases in Russia during 2009-2010 and 1302, 135 and 29 cases in the 2010-2011, 2012-2013 and 2013-2014 seasons respectively. The on average short duration (7.8±5 days) of lethal cases of Influenza A(H1N1)pdm09 infections in Russia suggests primary viral rather than secondary bacterial pneumonia. Hemorrhagic syndrome was recorded in 36.6% of patients. An examination of 221 lung samples from lethal influenza cases for the presence of bacterial DNA that could cause pneumonia did not reveal bacterial superinfections in 86% of cases. Molecular-genetic analyses of Influenza A(H1N1)pdm09 viruses from lethal and recovered cases were performed. Amino acids G and N at position 222 of the influenza virus hemagglutinin, which increase the affinity for the lower respiratory tract receptors, were detected more often in the lungs of patients who died than in respiratory swabs collected from recovered patients (p<0.0001 and p=0.007). Viruses harboring various mutations (222D/G/N/S) was significantly associated with lung samples compared with respiratory swabs from recovered patients (p<0.0001). Amino acid 222E, which increases the affinity for upper respiratory tract receptors, was found more frequently in recovered patients than in patients with lethal disease (27% versus 3%, p=0.005). Phylogenetic analysis identified an isolated cluster of viruses in the 2009-2010 season that harbored amino acid 222E, which could explain the high transmissibility of the virus at the beginning of the pandemic. Bayesian skyline plot implied a decline in the effective population size of Influenza A(H1N1)pdm09 viruses in Russia from 2010-2011 to 2011-2012, followed by an increase in 2012-2013; this trend was accompanied by the increased genetic diversity of the hemagglutinin antigenic sites. Mutations of viral RNA leading to oseltamivir resistance were found in 2.8% of tested patients during only 2010-2011 season. Deletions in the nucleoprotein cDNA were found in influenza viruses from two patients.
authors.affiliation: The Central Research Institute for Epidemiology of Rospotrebnadzor (CRIE), Department of Molecular Diagnostics and Epidemiology, 3A Novogireyevskaya Str., Moscow 111123, Russian Federation. Electronic address: svetlana.yatsyshina@pcr.ms.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Yatsyshina
authors.affiliation: The Central Research Institute for Epidemiology of Rospotrebnadzor (CRIE), Department of Molecular Diagnostics and Epidemiology, 3A Novogireyevskaya Str., Moscow 111123, Russian Federation. Electronic address: ania_renteeva@mail.ru.
authors.forename: Anna
authors.initials: A
authors.lastname: Renteeva
authors.affiliation: The Central Research Institute for Epidemiology of Rospotrebnadzor (CRIE), Department of Molecular Diagnostics and Epidemiology, 3A Novogireyevskaya Str., Moscow 111123, Russian Federation. Electronic address: andreideviatkin@gmail.com.
authors.forename: Andrei
authors.initials: A
authors.lastname: Deviatkin
authors.affiliation: The Central Research Institute for Epidemiology of Rospotrebnadzor (CRIE), Department of Molecular Diagnostics and Epidemiology, 3A Novogireyevskaya Str., Moscow 111123, Russian Federation. Electronic address: vorobyevakdl@yandex.ru.
authors.forename: Nadezhda
authors.initials: N
authors.lastname: Vorobyeva
authors.affiliation: The Central Research Institute for Epidemiology of Rospotrebnadzor (CRIE), Department of Molecular Diagnostics and Epidemiology, 3A Novogireyevskaya Str., Moscow 111123, Russian Federation. Electronic address: andrey.minenko@gmail.com.
authors.forename: Angrey
authors.initials: A
authors.lastname: Minenko
authors.affiliation: The Central Research Institute for Epidemiology of Rospotrebnadzor (CRIE), Department of Molecular Diagnostics and Epidemiology, 3A Novogireyevskaya Str., Moscow 111123, Russian Federation. Electronic address: anna.valdokhina@pcr.ms.
authors.forename: Anna
authors.initials: A
authors.lastname: Valdokhina
authors.affiliation: The Central Research Institute for Epidemiology of Rospotrebnadzor (CRIE), Department of Molecular Diagnostics and Epidemiology, 3A Novogireyevskaya Str., Moscow 111123, Russian Federation. Electronic address: mariyaelkina@yahoo.com.
authors.forename: Mariya
authors.initials: M
authors.lastname: Elkina
authors.affiliation: The Central Research Institute for Epidemiology of Rospotrebnadzor (CRIE), Department of Molecular Diagnostics and Epidemiology, 3A Novogireyevskaya Str., Moscow 111123, Russian Federation. Electronic address: konstantinkul@gmail.com.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Kuleshov
authors.affiliation: The Central Research Institute for Epidemiology of Rospotrebnadzor (CRIE), Department of Molecular Diagnostics and Epidemiology, 3A Novogireyevskaya Str., Moscow 111123, Russian Federation. Electronic address: german@pcr.ru.
authors.forename: German
authors.initials: G
authors.lastname: Shipulin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007223:Infant; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics; D007251:Influenza, Human / Q000401:mortality / Q000821:virology*; D008168:Lung / Q000821:virology; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D009698:Nucleoproteins / Q000235:genetics*; D010802:Phylogeny; D017384:Sequence Deletion; D014764:Viral Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: D009698:Nucleoproteins; D014764:Viral Proteins
keywords: Deletions; Influenza; Influenza virus; Molecular methods; Mutations; Pneumonia