A possible association of fatal pneumonia with mutations of pandemic influenza A/H1N1 sw1 virus in the receptor-binding site of the HA1 subunit

The paper gives the results of sequence analysis of 150 positive samples in real-time RT-PCR, including 47 autopsy materials from patients (including 10 pregnant women), who died from fatal pneumonia mainly in November-December 2009, in whom the lifetime etiological diagnosis had not been made and h...

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Published in:	Voprosy virusologiĭ Vol. 55; no. 4; p. 4
Main Authors:	L'vov, D K, Burtseva, E I, Prilipov, A G, Bogdanova, V S, Shchelkanov, M Iu, Bovin, N V, Samokhvalov, E I, Fediakina, I T, Deriabin, P G, Kolobukhina, L V, Shtyria, Iu A, Shevchenko, E S, Malyshev, N A, Merkulova, L N, Bazarova, M V, Maslov, A I, Ishchenko, N M, Iskhakova, E A, Al'khovskiĭ, S V, Grebennikova, T V, Sadykova, G K, L'vov, D N, Zhuravleva, M M, Iamnikova, S S, Shliapnikova, O V, Poglazov, A B, Trushakova, S V, Lavrishcheva, V V, Aristova, V A, Proshina, E S, Vereshchagin, N N, Kuz'michev, A G, Iashkulov, K B, Dzhambinov, S D, Bushkieva, B Ts, Eliseeva, S M, Bystrakov, S I, Sokolova, I A, Dzhaparidzhe, N I, Ledenev, Iu A, Rosolovskiĭ, A P, Gareev, R V, Boldyreva, V V, Anan'ev, V Iu, Baranov, N I, Gorelikov, V N, Garbuz, Iu A, Reznik, V I, Ivanov, L I, Zdanovskaia, N N, Sergeeva, N M, Podolianko, I A, Elovskiĭ, O V, Gromova, M A, Kalaeva, E E, Grigor'ev, S N, Eremeeva, Iu V, Dovgal', M V, Fedelesh, I Iu, Sakharova, E A, Burtnik, V I, Avdoshina, L N, Shapiro, N P, Maslov, D V, Ianovich, V A, Ott, V A, Lebedev, G B
Format:	Journal Article
Language:	Russian
Published:	Russia (Federation) 01-07-2010
Subjects:	Binding Sites - genetics Disease Outbreaks Female Hemagglutinin Glycoproteins, Influenza Virus - genetics Hemagglutinin Glycoproteins, Influenza Virus - metabolism Humans Influenza A Virus, H1N1 Subtype - genetics Influenza A Virus, H1N1 Subtype - pathogenicity Influenza, Human - epidemiology Influenza, Human - mortality Influenza, Human - virology Lung - virology Male Pneumonia, Viral - epidemiology Pneumonia, Viral - mortality Pneumonia, Viral - virology Polymerase Chain Reaction Pregnancy Pregnancy Complications, Infectious - epidemiology Pregnancy Complications, Infectious - mortality Pregnancy Complications, Infectious - virology Protein Subunits - genetics Protein Subunits - metabolism Receptors, Virus - metabolism Russia - epidemiology Sequence Analysis, Protein Virulence Russia
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Summary:	The paper gives the results of sequence analysis of 150 positive samples in real-time RT-PCR, including 47 autopsy materials from patients (including 10 pregnant women), who died from fatal pneumonia mainly in November-December 2009, in whom the lifetime etiological diagnosis had not been made and hence no early etiotropic therapy performed. 70% of the primary materials from the deceased patients were found to have pandemic influenza A(H1N1) v mutants in the lung tissue with D222G (15%), D222N (15%), D222E (2%) substitutions, as well as a mixture of mutants (38%). Nasopharyngeal lavages from 3 Chukotka deceased patients exhibited only consensus (nonmutant) D222 virus variants; there was a mixture of consensus and mutant virus variants in the trachea and a mixture of mutant ones in the lung. Preliminary data from the study of the interaction of the hemagglutinin of two strains having D222G and D222N mutations with 9 oligosaccharides imitating the variants of cell receptors for influenza A virus suggest that there is a double receptor specificity for alpha2'-3' and alpha2'-6'-sialosides with a preponderance of alpha2'-3'-specificity. Further spread of the mutants that have acquired a high virulence and preserved their capacity for the respiratory route of human infection may lead to the situation similar to that seen in the 1918-1919 pandemic. Another scenario for evolution of the virus is to preserve its receptor specificity for alpha2'-3'-sialosides and high virulence with losses of alpha2'-6' specificity and capacity for aerosol transmission, by damping the pandemic.
ISSN:	0507-4088