Amino acid polymorphism at residue 222 of the receptor-binding site of the hemagglutinin of the pandemic influenza A(H1N1)pdm09 from patients 166 with lethal virus pneumonia in 2012-2014

K. G. Krasnoslobodtsev; Краснослободцев К. Г.; D. K. Lvov; Львов Д. К.; S. V. Alkhovsky; Альховский С. В.; E. I. Burtseva; Бурцева Е. И.; I. T. Fedyakina; Федякина И. Т.; L. V. Kolobukhina; Колобухина Л. В.; E. S. Kirillova; Кириллова Е. С.; S. V. Trushakova; Трушакова С. В.; T. A. Oskerko; Оскерко Т. А.; M. Yu. Shchelkanov; Щелканов М. Ю.; P. G. Deryabin; Дерябин П. Г.

doi:10.18821/0507-4088-2016-61-4-166-171

Amino acid polymorphism at residue 222 of the receptor-binding site of the hemagglutinin of the pandemic influenza A(H1N1)pdm09 from patients 166 with lethal virus pneumonia in 2012-2014

Authors: Krasnoslobodtsev K.G.¹, Lvov D.K.¹, Alkhovsky S.V.¹, Burtseva E.I.¹, Fedyakina I.T.¹, Kolobukhina L.V.¹, Kirillova E.S.¹, Trushakova S.V.¹, Oskerko T.A.¹, Shchelkanov M.Y.¹, Deryabin P.G.¹
Affiliations:
1. «Federal Research Centre of Epidemilogy and Microbiology named after the honorary academician N.F. Gamaleya»
Issue: Vol 61, No 4 (2016)
Pages: 166-171
Section: ORIGINAL RESEARCH
URL: https://ogarev-online.ru/0507-4088/article/view/117887
DOI: https://doi.org/10.18821/0507-4088-2016-61-4-166-171
ID: 117887

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Abstract

Survey data from autopsy specimens from patients who died from pneumonia caused by the influenza A(H1N1) pdm09 in 2012-2014 and mutant forms of influenza virus in these patients (position 222 in the receptor-binding region of hemagglutinin) were presented. In total, according to aggregate data, obtained with three different methods (sequencing, next-generation sequencing (NGS), virus isolation) mutant viruses were detected in 17 (41%) from 41 patients. The proportion of the mutant forms in viral populations ranged from 1% to 69.2%. The most frequent mixture was the wild type (D222) and mutant (D222G), with proportion of mutant type ranged from 3.3% to 69.2% in the viral population. Mutation D222N (from 1.1% to 5.5%) was found rarely. Composition of the viral population from one patient is extremely heterogeneous: in left lung there was only wild type D222, meantime in right lung - mixture of mutant forms 222D/N/G (65.4/32.5/1.1%), in trachea - mixture 222D/G/Y/A (61.8/35.6/1.2/1.4%, respectively), and in bronchi compound of 222D/G/N/A (64.3/33.7/1/1%, respectively) were detected. The obtained data indicate that the process of adaptation of the virus in the lower respiratory tract is coupled with the appearance of different virus variants with mutations in the receptor-binding region. Mutant forms of the virus are observed in the lower respiratory tract of the majority of patients with lethal viral pneumonia. However, if they are a minor part of the population, they cannot be detected by the method of conventional sequencing. They can be identified using the NGS methods.

Keywords

A (H1N1)pdm09, next-generation sequencing, influenza, hemagglutinin, A(H1N1)pdm09, next-generation sequencing, receptor specificity, receptor-binding site, a2-3-sialosides, viral pneumonia

References

Львов Д.К., Бурцева Е.И., Прилипов А.Г., Богданова В.С., Щелканов М.Ю., Бовин Н.В. и др. Возможная связь летальной пневмонии с мутациями пандемического вируса гриппа A/H1N1swl в рецепторсвязывающем сайте субъединицы HA1 гемагглютинина. Вопросы вирусологии. 2010; (4): 4-9.
Львов Д.К., Малышев Н.А., Колобухина Л.В., Меркулова Л.Н., Бурцева Е.И., Щелканов М.Ю. и др. Грипп, вызванный новым пандемическим вирусом А/H1N1swl: клиника, диагностика, лечение. Методические рекомендации. М.; 2009.
Львов Д.К., Бурцева Е.И., Прилипов А.Г., Богданова В.С., Щелканов М.Ю., Бовин Н.В. и др. Распространение нового пандемического вируса гриппа A (H1N1)v в России. Вопросы вирусологии. 2010; 55 (3): 4-9.
Львов Д.К., Щелканов М.Ю., Бовин Н.В., Малышев Н.А., Чучалин А.Г., Колобухина Л.В. и др. Корреляция между рецепторной специфичностью штаммов пандемического вируса гриппа A (H1N1) pdm09, изолированных в 2009-2011 гг., структурой рецепторсвязывающего сайта и вероятностью развития летальной первичной вирусной пневмонии. Вопросы вирусологии. 2012; 57 (1): 14-7.
Львов Д.К., Яшкулов К.Б., Прилипов А.Г., Бурцева Е.И., Щелканов М.Ю., Шляпникова О.В. и др. Обнаружение аминокислотных замен аспарагиновой кислоты на глицин и аспарагин в рецепторсвязывающем сайте гемагглютинина в вариантах пандемического вируса гриппа A/H1N1 от больных с летальным исходом и со среднетяжелой формой заболевания. Вопросы вирусологии. 2010; 55 (3): 15-9.
Соминина А.А., Бурцева Е.И., Лобова Т.Г., Коновалова Н.И., Гудкова Т.М., Литвинова О.М. и др. Выделение вирусов гриппа в клеточных культурах и куриных эмбрионах и их идентификация. Методические рекомендации. М.; 2006.
Gilca R., De Serres G., Boulianne N., Ouhoummane N., Papenburg J., Douville-Fradet M. et al. Risk factors for hospitalization and severe outcomes of 2009 pandemic H1N1 influenza in Quebec, Canada. Influenza Other Respir. Viruses. 2011; 5 (4): 247-55.
Laura G.M., Sonja A.R., Denise J.J. 2009 pandemic influenza A (H1N1) in pregnancy: a systematic review of the literature. Am. J. Obstet. Gynecol. 2011; 205 (1): 10-8.
Ruggiero T., Rosa F., Cerutti F., Pagani N., Allice T., Stella M.L. et al. A (H1N1) pdm09 hemagglutinin D222G and D222N variants are frequently harbored by patients requiring extracorporeal membrane oxygenation and advanced respiratory assistance for severe A (H1N1) pdm09 infection. Influenza Other Respir. Viruses. 2013; 7 (6): 1416-26.
Shinya K., Ebina M., Yamada S., Ono M., Kasai N., Kawaoka Y. Avian flu: influenza virus receptors in the human airway. Nature. 2006; 440 (7083): 435-6.
Chunli W., Xiaowen C., Xin W., Xing L., Fan Y., Tao L. et al. Clinical and molecular characteristics of the 2009 pandemic influenza H1N1 infection with severe or fatal disease from 2009 to 2011 in Shenzhen, China. J. Med. Virol. 2013; 85 (3): 405-12.
Zehender G., Pariani E., Piralla A., Lai A., Gabanelli E., Ranghiero A. et al. Reconstruction of the evolutionary dynamics of the A (H1N1) pdm09 influenza virus in Italy during the pandemic and postpandemic phases. PLoS One. 2012; 7 (11): e47517.
Kong W., Liu L., Wang Y., Gao H., Wei K., Sun H. et al. Hemagglutinin mutation D222N of the 2009 pandemic H1N1 influenza virus alters receptor specificity without affecting virulence in mice. Virus Res. 2014; 189: 79-86.
Zhang W., Shi Y., Qi J., Gao F., Li Q., Fan Z. et al. Molecular basis of the receptor binding specificity switch of the hemagglutinins from both the 1918 and 2009 pandemic influenza A viruses by a D225G substitution. J. Virol. 2013; 87 (10): 5949-58.
Chutinimitkul S., Herfst S., Steel J., Lowen A.C., Ye J., van Riel D. et al. Virulence-associated substitution D222G in the hemagglutinin of 2009 pandemic influenza A (H1N1) virus affects receptor binding. J. Virol. 2010; 84 (22): 11 802-13.
Chen Z., Wang W., Zhou H., Suguitan A.L., Shambaugh C., Kim L. et al. Generation of live attenuated novel influenza virus A/California/7/09 (H1N1) vaccines with high yield in embryonated chicken eggs. J. Virol. 2009; 84 (1): 44-51.
Kilander A., Rykkvin R., Dudman S.G., Hungnes O. Observed association between the HA1 mutation D222G in the 2009 pandemic influenza A (H1N1) virus and severe clinical outcome, Norway 2009-2010. Euro Surveill. 2010; 15 (9). pii: 19498.
Wedde M., Wählisch S., Wolff T., Schweiger B. Predominance of HA-222D/G polymorphism in influenza A (H1N1)pdm09 viruses associated with fatal and severe outcomes recently circulating in Germany. PloS One. 2013; 8 (2): e57059.

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Amino acid polymorphism at residue 222 of the receptor-binding site of the hemagglutinin of the pandemic influenza A(H1N1)pdm09 from patients 166 with lethal virus pneumonia in 2012-2014

Full Text

Abstract

Keywords

About the authors

References

Supplementary files