Influence of single amino acid substitutions in the hemagglutinin on the antigenic and receptor-binding properties of influenza virus B/Florida/04/2006 of Yamagata-like evolutionary lineage

Influenza A and B viruses use sialylated oligosaccharide chains expressed on the surface of a host cell as the cell entry receptors. The type of the bond between sialic acid (SA) and the neighboring galactose residue (Gal) is one of the main characteristics that define the type of receptor. Influenza viruses recognize SAα2-3Gal- or SAα2-6Gal-structures on the surface of the cells. Influenza A viruses of avian origin bind α2-3-sialylated glycans, while the human strains bind preferentially α2-6-sialylated ones. However, the receptor-binding specificity of influenza B viruses has not been characterized sufficiently so far. In this study, we selected the escape mutants of influenza B/Florida/04/2006 strain (Yamagata-like lineage) using monoclonal antibodies (mAb) to hemagglutinin (HA). The analysis of the amino acid sequences of mAb-induced escape mutants revealed the single amino acid substitutions 40Tyr→His, 85His→Tyr, 202Asn→Lys and 242Ser→Arg in 10F4-, 8Н11-, 8Н3- and 9А3-induced HA variants, correspondingly. It was shown that the single amino acid substitutions 202Asn→Lys and 242Ser→Arg alter the receptor-binding specificity of the influenza B virus. These findings are important for the understanding of the influence of individual amino acid residues in HA on the receptor-binding properties of influenza B Yamagata-like lineage viruses and allow us to predict the possible ways of their evolution.Influenza A and B viruses use sialylated oligosaccharide chains expressed on the surface of a host cell as the cell entry receptors. The type of the bond between sialic acid (SA) and the neighboring galactose residue (Gal) is one of the main characteristics that define the type of receptor. Influenza viruses recognize SAα2-3Gal- or SAα2-6Gal-structures on the surface of the cells. Influenza A viruses of avian origin bind α2-3-sialylated glycans, while the human strains bind preferentially α2-6-sialylated ones. However, the receptor-binding specificity of influenza B viruses has not been characterized sufficiently so far. In this study, we selected the escape mutants of influenza B/Florida/04/2006 strain (Yamagata-like lineage) using monoclonal antibodies (mAb) to hemagglutinin (HA). The analysis of the amino acid sequences of mAb-induced escape mutants revealed the single amino acid substitutions 40Tyr→His, 85His→Tyr, 202Asn→Lys and 242Ser→Arg in 10F4-, 8Н11-, 8Н3- and 9А3-induced HA variants, correspondingly. It was shown that the single amino acid substitutions 202Asn→Lys and 242Ser→Arg alter the receptor-binding specificity of the influenza B virus. These findings are important for the understanding of the influence of individual amino acid residues in HA on the receptor-binding properties of influenza B Yamagata-like lineage viruses and allow us to predict the possible ways of their evolution

Development of the cell-ELISA test for the subtype identification of circulating influenza A(H1) and A(H3) viruses

The sensitive version of cell-ELISA was developed for the subtype-specific differentiation of current influenza A(H1N1)pdm09 and A(H3N2) viruses that are circulating in the human population. This method is based on the estimation of virus reproduction in infected MDCK cells. The detection step of this method is an interaction of the subtype-specific monoclonal antibodies (mAbs) with the viral hemagglutinin (НА) molecule. The influenza A virus strains, isolated in the 2014 epidemic season, were used to validate this method.It was shown that when using mAbs # 1/ # 2 or # 4 at a concentration of 10-15 µg/ml, the developed variant of cell-ELISA was able to detect НА protein synthesized in the infected cells of influenza A(H3N2) and A(H1N1)pdm09 viruses, respectively.The developed method can be used for the identification of modern influenza A viruses with low hemagglutination activity, which is not possible by the conventional hemagglutination inhibition test.The sensitive version of cell-ELISA was developed for the subtype-specific differentiation of current influenza A(H1N1)pdm09 and A(H3N2) viruses that are circulating in the human population. This method is based on the estimation of virus reproduction in infected MDCK cells. The detection step of this method is an interaction of the subtype-specific monoclonal antibodies (mAbs) with the viral hemagglutinin (НА) molecule. The influenza A virus strains, isolated in the 2014 epidemic season, were used to validate this method. It was shown that when using mAbs # 1/ # 2 or # 4 at a concentration of 10-15 µg/ml, the developed variant of cell-ELISA was able to detect НА protein synthesized in the infected cells of influenza A(H3N2) and A(H1N1)pdm09 viruses, respectively. The developed method can be used for the identification of modern influenza A viruses with low hemagglutination activity, which is not possible by the conventional hemagglutination inhibition test

The influenza epidemic in Russia during the 2014–2015 season

The goal of this study was to compare the data on the intensity of the influenza A(H3N2) and B epidemic (especially the death toll) in the 2014–2015 season with the previous epidemic of the 2013-2014 season. The data on weekly morbidity, hospitalization, deaths from influenza, and acute respiratory diseases in different age groups of inhabitants of 59 cities located in 7 Federal districts of the Russian Federation were collected using the database of the Research Institute of Influenza.Analysis of this data showed that the influenza epidemic in 2014-2015 began earlier (in December) compared to the epidemic of 2013-2014, and spread mainly from Europe through Russia to the East. The intensity of the epidemic of 2014-2015 was higher compared to the previous one. The epidemic was more prevalent by regions and cities and a wider engagement of different age groups (except children up to 2 years of age) was observed. At the peak of the epidemic, the morbidity level was higher, the average duration of the epidemic was longer, and the number of patients among cities’ inhabitants (especially among children 7-14 years of age and adults) was higher than in the previous season. The rates of hospitalization with influenza and acute respiratory viral infections (ARVI) among patients older than 65 years were also higher (1.4 times) as well as the frequency of hospitalization with a diagnosis of “influenza” (2.7 times) and the number of deaths from laboratory confirmed influenza (1.8 times).Although the influenza pandemic virus strain A(H1N1)pdm09 was not the main causative agent of the 2015 epidemic and was distributed sporadically it still remained the leading cause of deaths from influenza in the course of this epidemic (45.5% of all cases). The deaths associated with this strain were recorded only in the European part of Russian Federation.The goal of this study was to compare the data on the intensity of the influenza A(H3N2) and B epidemic (especially the death toll) in the 2014–2015 season with the previous epidemic of the 2013-2014 season. The data on weekly morbidity, hospitalization, deaths from influenza, and acute respiratory diseases in different age groups of inhabitants of 59 cities located in 7 Federal districts of the Russian Federation were collected using the database of the Research Institute of Influenza. Analysis of this data showed that the influenza epidemic in 2014-2015 began earlier (in December) compared to the epidemic of 2013-2014, and spread mainly from Europe through Russia to the East. The intensity of the epidemic of 2014-2015 was higher compared to the previous one. The epidemic was more prevalent by regions and cities and a wider engagement of different age groups (except children up to 2 years of age) was observed. At the peak of the epidemic, the morbidity level was higher, the average duration of the epidemic was longer, and the number of patients among cities’ inhabitants (especially among children 7-14 years of age and adults) was higher than in the previous season. The rates of hospitalization with influenza and acute respiratory viral infections (ARVI) among patients older than 65 years were also higher (1.4 times) as well as the frequency of hospitalization with a diagnosis of “influenza” (2.7 times) and the number of deaths from laboratory confirmed influenza (1.8 times). Although the influenza pandemic virus strain A(H1N1)pdm09 was not the main causative agent of the 2015 epidemic and was distributed sporadically it still remained the leading cause of deaths from influenza in the course of this epidemic (45.5% of all cases). The deaths associated with this strain were recorded only in the European part of Russian Federation

Changes in the antigenic and genetic structure of influenza viruses: analysis of surveillance data of influenza A and B in Russia in 2006-2013

The goal of this research project was to study the natural variability of human influenza A and B viruses based on the analysis of the population structure of influenza viruses, circulating in Russia in 2006-2013, in order to determine the direction of their genetic and antigenic drift by comparison to the WHO reference strains. Our results proved that during that period significant changes occurred in the genetic structure of influenza viruses, their phylogenetic affiliation, as well as their sensitivity to antiviral drugs. According to the surveillance data, the percentage of influenza A(H1N1) viruses among patients with influenza-like illness or acute respiratory infection gradually decreased from 42% of the total number of influenza viruses in 2006-2007 to 19% in 2008- 2009. Influenza A(H1N1) viruses are characterized by «silent» variability that manifests in the gradual accumulation of amino acid substitutions in the minor undetectable group of viruses.The share of influenza A(H3N2) viruses varied from 10% in the 1st post pandemic year to approx. 60% in 2008-2009 and 2011- 2012 epidemic seasons. All of the influenza A strains isolated during the last years of the period, covered in this study, were found to be susceptible to neuraminidase inhibitors and resistant to adamantane antivirals.Influenza B viruses of both Yamagata and Victoria lineages circulated in Russia in the period from 2006 to 2013. The vast majority of these influenza B viruses belonged to the Victoria lineage. Phylogenetic and antigenic analyses of influenza B viruses have demonstrated a gradual drift of Russian isolates from the reference strains. No changes leading to resistance to oseltamivir or zanamivir were found in influenza B strains isolated until 2013.The goal of this research project was to study the natural variability of human influenza A and B viruses based on the analysis of the population structure of influenza viruses, circulating in Russia in 2006-2013, in order to determine the direction of their genetic and antigenic drift by comparison to the WHO reference strains. Our results proved that during that period significant changes occurred in the genetic structure of influenza viruses, their phylogenetic affiliation, as well as their sensitivity to antiviral drugs. According to the surveillance data, the percentage of influenza A(H1N1) viruses among patients with influenza-like illness or acute respiratory infection gradually decreased from 42% of the total number of influenza viruses in 2006-2007 to 19% in 2008- 2009. Influenza A(H1N1) viruses are characterized by «silent» variability that manifests in the gradual accumulation of amino acid substitutions in the minor undetectable group of viruses. The share of influenza A(H3N2) viruses varied from 10% in the 1st post pandemic year to approx. 60% in 2008-2009 and 2011- 2012 epidemic seasons. All of the influenza A strains isolated during the last years of the period, covered in this study, were found to be susceptible to neuraminidase inhibitors and resistant to adamantane antivirals. Influenza B viruses of both Yamagata and Victoria lineages circulated in Russia in the period from 2006 to 2013. The vast majority of these influenza B viruses belonged to the Victoria lineage. Phylogenetic and antigenic analyses of influenza B viruses have demonstrated a gradual drift of Russian isolates from the reference strains. No changes leading to resistance to oseltamivir or zanamivir were found in influenza B strains isolated until 2013

ОСОБЕННОСТИ КЛИНИЧЕСКОГО ТЕЧЕНИЯ ОСТРЫХ РЕСПИРАТОРНЫХ ЗАБОЛЕВАНИЙ, ВЫЗВАННЫХ АДЕНОВИРУСАМИ ЭПИДЕМИЧЕСКИ ЗНАЧИМЫХ СЕРОТИПОВ

The objective: To investigate etiological structure of adenoviral diseases in young people from organized groups and the clinical features of acute respiratory disease caused by different serotypes of adenovirus were identified.Materials and methods: A total 382 patients with adenovirusinfections were investigated. Virus isolation from nasopharyngeal swabs was carried out in cell cultures Vero, HeLa, Hep-2. Typing of adenoviruses was performed by virus neutralization test with polyclonal rabbit subtype specific sera. The average (M), standard deviation (SD) and frequency of occurrence (%) of clinical signs (respiratory and non-respiratory syndromes of pneumonia, protracted and recurrent course was calculated. Significance of the differences (p<0,05) of average frequency of cases compared to independent group of patients was evaluated by Student t-test and criterion φ2 (phi – square) Fischer, respectively.Results: As result of investigation 199 adenovirus strains (52,1 %) were isolated. 183 strains were serotyped: 64 (32,2 %) – 3 serotype, 42 (21,1 %) – 4 serotype, 38 (19,1 %) – 7 serotype, 15 (7,5 %) – 5 serotype, 11 (5,5 %) – 21 serotype, 8 (4,0 %) – 1 serotype, 3 (1,5 %) – 2 serotype, 2 (1,0 %) – 6 serotype. In assessing the features of the clinical course of adenoviral infection caused by the most actual serotypes (3, 4, 7) of adenovirus revealed that duration of diseases caused by serotype 7 was significantly longer and remained febrile fever (4,3±2,74 days, p<0,05), rhinitis (9,4±6,01 days, p<0,05), pharyngitis (7,9±2,87 days, p<0,05), laryngitis (7,3±2,87 days, p<0,05) and bronchitis (11,8±8,03 days, p<0,05), tonsillitis (63,0%, φ2=12,6, p<0,05), lymphadenopathy (63,0%, φ2=4,1, p<0,05), and pneumonia (34,2%, φ2=3,84, p<0,05) were registered significantly more frequently.Conclusion: The study showed that the adenoviruses of 3, 4 and 7 serotype have the greatest epidemiological significance. Clinical features of adenoviral diseases caused by 7 serotype were manifested in more frequent registration of non-respiratory syndromes and the development of pneumonia.Цель – исследовать этиологическую структуру аденовирусных заболеваний у лиц молодого возраста из организованных коллективов и выявить особенности клинического течения ОРЗ, вызванных различными серотипами аденовирусов.Материалы и методы: обследовано 382 больных аденовирусными заболеваниями. Выделение вирусов из носоглоточных мазков проводили на культурах клеток Vero, HeLa, Hep-2. Типирование аденовирусов проводили в реакции нейтрализации с поликлональными субтипоспецифическими кроличьими антисыворотками. Рассчитывали среднюю (M), стандартное отклонение (SD) и частоту встречаемости (%) клинических признаков (респираторных и нереспираторных синдромов, развития пневмоний, затяжного и рецидивирующего течения). Достоверность различия (p<0,05) средней, частоты встречаемости случаев в сравниваемых независимых группах оценивали по t-критерию Стьюдента и критерию φ2 (фи-квадрат) Фишера соответственно.Результаты: выделено 199 штаммов аденовирусов (52,1%). Серотипировано 183 штамма: 64 (32,2%) – 3-го серотипа, 42 (21,1%) – 4-го серотипа, 38 (19,1%) – 7-го серотипа, 15 (7,5%) – 5-го серотипа, 11 (5,5%) – 21-го серотипа, 8 (4,0%) – 1-го серотипа, 3 (1,5%) – 2-го серотипа, 2 (1,0%) – 6-го серотипа. При оценке особенностей клинического течения аденовирусных заболеваний, вызванных актуальными серотипами (3, 4, 7) аденовирусов, выявлено, что при заболеваниях, вызванных 7-м серотипом, достоверно дольше сохранялись фебрильная лихорадка (4,3±2,74 дня, p<0,05), ринит (9,4±6,01 дня, p<0,05), фарингит (7,9±2,87, p<0,05), ларингит (7,3±2,87, p<0,05) и бронхит (11,8±8,03, p<0,05), достоверно чаще наблюдали тонзиллит (63,0%, φ2=12,6, p<0,05), лимфаденопатию (63,0%, φ2=4,1, p<0,05) и пневмонию (34,2%, φ2=3,84, p<0,05).Заключение: исследование показало, что наибольшей эпидемиологической значимостью обладают аденовирусы 3-го, 4-го и 7-го серотипов, клиническими особенностями аденовирусных заболеваний, вызванных 7-м серотипом вируса, являются более частая регистрация нереспираторных синдромов и развитие пневмонии

Two years of experience in hospital surveillance for the severe influenza like illnesses in St. Petersburg: etiology, clinical characterization of diseases, antigenic and genetic properties of isolated influenza viruses

In this paper, we analyze the etiology of the diseases occurring during two consecutive influenza epidemic seasons in St. Petersburg, Russian Federation. The analysis is based on the results of the PCR diagnostics of the clinical samples collected from patients hospitalized in three St. Petersburg hospitals with influenza like illnesses (ILI). It was shown that the influenza virus A(H1N1)pdm09 was the dominant causative agent during the 2012-2013 epidemic season while, in the 2013-2014 season, A(H3N2) virus was predominant among adults and children. The influenza B virus activity was high in the 2012-2013 season and low in the 2013-2014 season. During both seasons, the main causative agent for the hospitalization of young children was respiratory syncytial virus (RSV), followed by rhinovirus and influenza virus. The rate of involvement of parainfluenza, adenovirus, metapneumovirus and coronavirus was low and was negligible for bocavirus. Children 0-2 and 3-6 years old formed the group of patients that was affected by acute respiratory infection agents the most. Children younger than 3 months old were the major group of the intensive care unit (ICUs) patients and only 27.5% of them were adults. RSV and rhinovirus were the leading cause of ILI among the children admitted to ICU. Among the adult patients admitted to the ICU, only influenza A(H1N1)pdm09, A(H3N2) and B viruses were detected during both influenza seasons.According to the results of the antigenic and genetic analysis, most influenza A(H1N1)pdm09 and A(H3N2) viruses circulating in St. Petersburg matched the vaccine strains recommended by the WHO for vaccine composition in the 2012-2013 and 2013-2014 seasons.In this paper, we analyze the etiology of the diseases occurring during two consecutive influenza epidemic seasons in St. Petersburg, Russian Federation. The analysis is based on the results of the PCR diagnostics of the clinical samples collected from patients hospitalized in three St. Petersburg hospitals with influenza like illnesses (ILI). It was shown that the influenza virus A(H1N1)pdm09 was the dominant causative agent during the 2012-2013 epidemic season while, in the 2013-2014 season, A(H3N2) virus was predominant among adults and children. The influenza B virus activity was high in the 2012-2013 season and low in the 2013-2014 season. During both seasons, the main causative agent for the hospitalization of young children was respiratory syncytial virus (RSV), followed by rhinovirus and influenza virus. The rate of involvement of parainfluenza, adenovirus, metapneumovirus and coronavirus was low and was negligible for bocavirus. Children 0-2 and 3-6 years old formed the group of patients that was affected by acute respiratory infection agents the most. Children younger than 3 months old were the major group of the intensive care unit (ICUs) patients and only 27.5% of them were adults. RSV and rhinovirus were the leading cause of ILI among the children admitted to ICU. Among the adult patients admitted to the ICU, only influenza A(H1N1)pdm09, A(H3N2) and B viruses were detected during both influenza seasons. According to the results of the antigenic and genetic analysis, most influenza A(H1N1)pdm09 and A(H3N2) viruses circulating in St. Petersburg matched the vaccine strains recommended by the WHO for vaccine composition in the 2012-2013 and 2013-2014 seasons

Влияние единичных аминокислотных замен в гемагглютинине вируса гриппа В/Флорида/04/2006 ямагатской эволюционной линии на антигенные и рецепторсвязывающие свойства

Influenza A and B viruses use sialylated oligosaccharide chains expressed on the surface of a host cell as the cell entry receptors. Type of the bond between sialic acid (SA) and neighboring galactose residue (Gal) is one of the main characteristics that define the type of receptor. Influenza viruses recognize SAα2-3Gal- or SAα2-6Gal-structures on the surface of the cells. The Yamagata-like virus strains are predominantly bound to α2,6-sialylated glycans, while Victoria-like strains are bound to both α2,3- and α2,6-sialylated glycans. However, the receptor-binding specificity of influenza B viruses has not been characterized enough. In this study, we selected escape mutants of influenza B/Florida/04/2006 strain (Yamagata-like lineage) using monoclonal antibodies (mAb) to hemagglutinin (HA). Analysis of the amino acid sequences of mAb-induced escape-mutants revealed the single amino acid substitutions 40Tyr→His, 85His→Tyr, 202Asn→Lys and 242Ser→Arg in 10F4-, 8Н11-, 8Н3- and 9А3-induced HA variants, correspondingly. It was shown that the single amino acid substitutions 202Asn→Lys and 242Ser→Arg alter the receptor-binding specificity of the influenza B virus. These findings are important for the understanding of the influence of individual amino acid residues in HA on the receptor-binding properties of influenza B Yamagata-like lineage viruses and allow us to predict the possible ways of their evolution.Известно, что рецептором для проникновения в клетку хозяина для вирусов гриппа A и В служат углеводные цепи, терминированные остатками нейраминовой кислоты. Тип связи между сиаловой кислотой (sialic acid, SA) и соседним остатком галактозы (Gal) является одной из главных характеристик, определяющих тип рецептора. Вирусы гриппа узнают на поверхности клетки SAα2-3Gal- или SAα2-6Gal-структуры. Птичьи изоляты вирусов гриппа A связываются с SAα2-3- сиалированными цепями, тогда как вирусы гриппа А человека – с SAα2-6Gal. Рецепторсвязывающая специфичность вирусов гриппа B изучена мало, однако известно, что вирусы разновидности Ямагата преимущественно узнают олигосахариды, терминированные SAα2-6Gal, тогда как вирусы генетической линии Виктория узнают оба типа сиалозидов. Используя четыре вируснейтрализующих моноклональных антитела (монАТ): 10F4, 8Н11, 8Н3 и 9А3, – мы получили эскейп-мутанты вируса гриппа В/Флорида/04/2006 ямагатской линии. При анализе последовательности гемагглютинина (HA) выявлено, что НА эскейп-мутантов, индуцированных монАТ 10F4, 8Н11, 8Н3 и 9А3, несут следующие единичные аминокислотные замены: 40Tyr→His, 85His→Tyr, 202Asn→Lys и 242Ser→Arg соответственно. Показано, что замены 202Asn→Lys и 242Ser→Arg приводят к изменению рецепторсвязывающей специфичности вируса. Полученные данные имеют важное значение для понимания роли отдельных аминокислотных остатков HA в формировании рецепторсвязывающих свойств вирусов гриппа В ямагатской эволюционной линии, что позволяет прогнозировать возможные пути эволюции этих вирусов

Использование микрокультурального иммуноферментного анализа для субтиповой идентификации циркулирующих вирусов гриппа А(Н1) и А(Н3)

The sensitive version of cell-ELISA was developed for the subtype-specific differentiation of current influenza A(H1N1)pdm09 and A(H3N2) viruses that are circulating in the human population. This method is based on the estimation of virus reproduction in the infected MDCK cells. The detection step of this method is an interaction of the subtype-specific monoclonal antibodies (mAbs) with the viral hemagglutinin (НА). The influenza A virus strains, isolated in 2014 epidemic season, were used to validate this method. It was shown that by using mAb # 1/ # 2 or # 4 at a concentration of 10-15 µg / ml the developed variant of cell-ELISA allows the detection of НА protein, synthesized in the cells infected with influenza A(H3N2) or A(H1N1)pdm09 virus, respectively. The developed method can be used for identification of HA subtype of modern influenza A viruses with low HA activity, which is not possible by the conventional hemagglutination inhibition test.Разработан чувствительный вариант микрокультурального ИФА (cell-ELISA) для субтиповой дифференциации современных вирусов гриппа А(Н1N1)pdm09 и А(Н3N2), циркулирующих в человеческой популяции. Метод основан на оценке репродукции вируса в инфицированной культуре клеток MDCK c использованием на стадии детекции cубтип-специфичных моноклональных антител (mAb), взаимодействующих с гемагглютинином (HA) вируса гриппа. При отработке метода использованы штаммы вирусов гриппа A, выделенные из клинических образцов в эпидемический сезон 2014 года. Показано, что при использовании mAb #1/#2 или #4 в концентрации 10–15 мкг/мл разработанный вариант cell-ELISA позволяет детектировать синтезируемый в зараженных клетках белок HA соответственно вирусов гриппа А(H3N2) или A(H1N1)pdm09. Разработанный метод может быть использован для идентификации современных штаммов вируса гриппа А в процессе их репродукции в клеточной культуре MDCK, что позволяет проводить субтипирование вирусов с низкой гемагглютинирующей активностью, когда невозможно использовать общепринятый метод – реакцию торможения гемагглютинации (РТГА)

Эпидемия гриппа в России в сезон 2014–2015 гг.

The goal of this study was to compare the data on the intensity of the influenza A(H3N2) and B epidemic (especially the death toll) in 2014–2015 season with the previous epidemic of 2013-2014. The data on weekly morbidity, hospitalization, deaths from influenza and acute respiratory diseases in different age groups of inhabitants of 59 cities located in 7 Federal districts of the Russian Federation were collected using the database of the Research Institute of Influenza. Analysis of this data showed, that the influenza epidemic in 2014-2015 began earlier (in December), compared with the epidemic of 2013-2014, and spread mainly from Europe through Russia to the East. The intensity of the epidemic 2014-2015 was higher, compared to the previous one. The epidemic was more prevalent by regions and cities and wider engagement of different age groups (except children up to 2 years) was observed. At the peak of the epidemic the morbidity level was higher, the average duration of the epidemic was longer and the number of patients among cities inhabitants (especially among children 7-14 years of age and adults) was higher than in the previous season. The rates of hospitalization with influenza and ARI among patients older than 65 years were also higher (1.4 times) as well as frequency of hospitalization with a diagnosis of “influenza” (2.7 times) and the number of deaths from laboratory confirmed influenza (1.8 times). Although the pandemic influenza virus A(H1N1)pdm09, was not the main causative agent of the epidemic 2015, it still was the main cause of deaths from influenza (45.5% of all cases). In spite of influenza A(H1N1)pdm09 virus sporadic prevalence, deaths from it were reported only on the European part of territory of Russia.Целью работы было сравнение показателей интенсивности эпидемии гриппа, вызванной штаммами вирусов гриппа А(H3N2) и В, в сезон 2014–2015 гг. с предшествующей эпидемией 2013–2014 гг. Особое внимание уделено летальным исходам от гриппа. Использована база данных НИИ гриппа по еженедельной заболеваемости, госпитализации, летальным исходам от гриппа и ОРЗ в различных возрастных группах населения 59-ти наблюдаемых городов, расположенных в семи Федеральных округах Российской Федерации. По сравнению с эпидемией 2014 г. эпидемия гриппа в 2014–2015 гг. началась раньше (в декабре) и распространялась, в основном, с запада на восток – из Европы по территории России в восточном направлении. Показатели интенсивности эпидемии 2015 г., в сравнении с предыдущей, были выше в отношении распространенности по округам, городам и вовлеченности возрастных групп населения (кроме детей до 2-х лет). Показатели заболеваемости на пике эпидемии, средней продолжительности эпидемии, уровней заболеваемости населения в городах (особенно среди детей 7–14 лет и взрослого населения) были выше, чем в предыдущем сезоне. Участились и случаи госпитализации с гриппом и OPВИ среди лиц старше 65 лет (в 1.4 раза), среди госпитализированных повысилась доля больных с диагнозом «грипп» (в 2.7 раза) и число летальных исходов от лабораторно подтвержденного гриппа (в 1.8 раза). Штамм пандемического вируса гриппа, A(H1N1)pdm09, хотя и не был основным возбудителем эпидемии 2015 г., попрежнему стал основной причиной летальных исходов от гриппа (в 45.5% всех случаев); причем случаи смерти, ассоциированные с этим штаммом, регистрировали только на европейской территории России при спорадическом уровне его распространения