RESUMEN
Outbreaks of influenza, which is a contagious respiratory disease, occur throughout the world annually, affecting millions of people with many fatal cases. The D222G/N mutations in the hemagglutinin (HA) gene of A(H1N1)pdm09 are associated with severe and fatal human influenza cases. These mutations lead to increased virus replication in the lower respiratory tract (LRT) and may result in life-threatening pneumonia. Targeted NGS analysis revealed the presence of mutations in major and minor variants in 57% of fatal cases, with the proportion of viral variants with mutations varying from 1% to 98% in each individual sample in the epidemic season 2018-2019 in Russia. Co-occurrence of the mutations D222G and D222N was detected in a substantial number of the studied fatal cases (41%). The D222G/N mutations were detected at a low frequency (less than 1%) in the rest of the studied samples from fatal and nonfatal cases of influenza. The presence of HA D222Y/V/A mutations was detected in a few fatal cases. The high rate of occurrence of HA D222G/N mutations in A(H1N1)pdm09 viruses, their increased ability to replicate in the LRT and their association with fatal outcomes points to the importance of monitoring the mutations in circulating A(H1N1)pdm09 viruses for the evaluation of their epidemiological significance and for the consideration of disease prevention and treatment options.
Asunto(s)
Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Subtipo H1N1 del Virus de la Influenza A/fisiología , Gripe Humana/mortalidad , Análisis de Secuencia de ARN/métodos , Animales , Cadáver , Perros , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Subtipo H1N1 del Virus de la Influenza A/genética , Gripe Humana/epidemiología , Células de Riñón Canino Madin Darby , Mutación , Polimorfismo Genético , Prevalencia , Federación de Rusia/epidemiología , Replicación ViralRESUMEN
Data obtained from monitoring cases of severe influenza, cases of vaccinated individuals, and unique cases were used to describe influenza viruses that circulated in Russia in the 2018-2019 epidemic season. A high proportion of the mutations D222G/N in A(H1N1)pdm09 HA was detected in fatal cases. Viruses of the B/Victoria lineage with deletions in HA were detected in Russia, and a reassortant seasonal influenza A(H1N2) virus was identified. A C-terminal truncation in the NS1 protein was detected in a substantial proportion of A(H3N2) viruses.
Asunto(s)
Subtipo H1N2 del Virus de la Influenza A/aislamiento & purificación , Gripe Humana/virología , Genoma Viral , Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Humanos , Subtipo H1N2 del Virus de la Influenza A/clasificación , Subtipo H1N2 del Virus de la Influenza A/genética , Subtipo H3N2 del Virus de la Influenza A/genética , Subtipo H3N2 del Virus de la Influenza A/aislamiento & purificación , Filogenia , Virus Reordenados/clasificación , Virus Reordenados/genética , Virus Reordenados/aislamiento & purificación , Federación de Rusia , Estaciones del AñoRESUMEN
[This corrects the article DOI: 10.1371/journal.pone.0220401.].
RESUMEN
The 2017-2018 influenza epidemic season in Russia was characterized by a relatively low morbidity and mortality. We evaluated herd immunity prior to the 2017-2018 influenza season in hemagglutination inhibition assay, and performed characterization of influenza viruses isolated from severe or fatal influenza cases and from influenza cases in people vaccinated in the fall of 2017. During the 2017-2018 epidemic season, 87 influenza A and B viruses were isolated and viruses of the 75 influenza cases, including selected viral isolates and viruses analyzed directly from the original clinical material, were genetically characterized. The analyzed A(H1N1)pdm09 viruses belonged to clade 6B.1, B/Yamagata-like viruses belonged to clade 3, and B/Victoria-like viruses belonged to clade 1A and they were antigenically similar to the corresponding vaccine strains. A(H3N2) viruses belonged to clade 3C.2a and were difficult to characterize antigenically and the analysis indicated antigenic differences from the corresponding egg-grown vaccine strain. The next generation sequencing revealed the presence of D222/G/N polymorphism in the hemagglutinin gene in 32% of the analyzed A(H1N1)pdm09 lethal cases. This study demonstrated the importance of monitoring D222G/N polymorphism, including detection of minor viral variants with the mutations, in the hemagglutinin gene of A(H1N1)pdm09 for epidemiological surveillance. One strain of influenza virus A(H1N1)pdm09 was resistant to oseltamivir and had the H275Y amino acid substitution in the NA protein. All other isolates were susceptible to NA inhibitors. Prior to the 2017-2018 epidemic season, 67.4 million people were vaccinated, which accounted for 46.6% of the country's population. Just before the epidemic season 33-47% and 24-30% of blood sera samples collected within the territory of Russia showed the presence of protective antibody titers against vaccine strains of influenza A and influenza B/Victoria-like, respectively. Mass vaccination of the population had evidently reduced the severity of the flu epidemic during the 2017-2018 influenza epidemic season in Russia.
Asunto(s)
Alphainfluenzavirus/clasificación , Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Virus de la Influenza B/clasificación , Gripe Humana/epidemiología , Adolescente , Adulto , Niño , Preescolar , Farmacorresistencia Viral , Epidemias , Monitoreo Epidemiológico , Femenino , Pruebas de Inhibición de Hemaglutinación , Humanos , Lactante , Recién Nacido , Virus de la Influenza B/genética , Virus de la Influenza B/inmunología , Gripe Humana/virología , Alphainfluenzavirus/genética , Alphainfluenzavirus/inmunología , Masculino , Persona de Mediana Edad , Filogenia , Polimorfismo Genético , ARN Viral/genética , Federación de Rusia/epidemiología , Adulto JovenRESUMEN
Cyclamen europaeum tubers extract (CTE) with concentration commonly used for human rhinosinusitis treatment was tested as mucosal adjuvant in experimental intranasal immunization of guinea pigs with concentrated commercially available influenza trivalent vaccine and subsequent infection with influenza strain A/California/04/2009 H1N1pdm. Dual intranasal immunization with vaccine compound consisting of 7.5 µg of each hemagglutinin and 500 µg of CTE in 50 µl induced reciprocal GMT on day 21 after immunization 40 (5-640) against H1N1pdm; 43.20 (5-1280) against H3N2; 10.80 (5-80) against influenza B. Animals with HI titers 1/80 against cell-derived antigen were completely protected against challenge with A/California/04/2009 H1N1pdm09.