Y155H amino acid substitution in influenza A(H1N1)pdm09 viruses does not confer a phenotype of reduced susceptibility to neuraminidase inhibitors

The Y155H amino acid substitution in the neuraminidase gene (NA) has previously been associated with highly reduced inhibition by neuraminidase inhibitors in the seasonal H1N1 influenza A virus which circulated in humans before the 2009 pandemic. During the 2012/13 epidemic season in Spain, two A(H1N1)pdm09 viruses bearing the specific Y155H substitution in the NA were detected and isolated from two patients diagnosed with severe respiratory syndrome and pneumonia requiring admission to the intensive care unit. Contrary to what was observed in the seasonal A(H1N1) viruses, neither of the Y155H A(H1N1)pdm09 viruses described here showed a phenotype of reduced inhibition by NAIs as determined by the neuraminidase enzyme inhibition assay (MUNANA). High-throughput sequencing of the NA of both Y155H viruses showed that they were composed to >99% of H155 variants. We believe that this report can contribute to a better understanding of the biological significance of amino acid substitutions in the neuraminidase protein with regard to susceptibility of influenza viruses to neuraminidase inhibitors. This is of critical importance for optimal management of influenza disease patients.

Download Full-text

MOLECULAR AND GENETIC CHARACTERISTICS OF SURFACE AND NONSTRUCTURE PROTEINS OF PANDEMIC INFLUENZA VIRUSES A(H1N1)PDM09 IN 2015-2016 EPIDEMIC SEASON

Bulletin of Taras Shevchenko National University of Kyiv Series Biology ◽

10.17721/1728_2748.2016.72.44-48 ◽

2016 ◽

Vol 72 (2) ◽

pp. 44-48

Author(s):

O. Smutko ◽

L. Radchenko ◽

A. Mironenko

Keyword(s):

Amino Acid ◽

Pandemic Influenza ◽

Influenza A ◽

Phylogenetic Trees ◽

Influenza Viruses ◽

Amino Acid Substitutions ◽

Ns1 Protein ◽

Genetic Characteristics ◽

Epidemic Season ◽

Influenza A H1n1

The aim of the present study was identifying of molecular and genetic changes in hemaglutinin (HA), neuraminidase (NA) and non-structure protein (NS1) genes of pandemic influenza A(H1N1)pdm09 strains, that circulated in Ukraine during 2015-2016 epidemic season. Samples (nasopharyngeal swabs from patients) were analyzed using real-time polymerase chain reaction (RTPCR). Phylogenetic trees were constructed using MEGA 7 software. 3D structures were constructed in Chimera 1.11.2rc software. Viruses were collected in 2015-2016 season fell into genetic group 6B and in two emerging subgroups, 6B.1 and 6B.2 by gene of HA and NA. Subgroups 6B.1 and 6B.2 are defined by the following amino acid substitutions. In the NS1 protein were identified new amino acid substitutions D2E, N48S, and E125D in 2015-2016 epidemic season. Specific changes were observed in HA protein antigenic sites, but viruses saved similarity to vaccine strain. NS1 protein acquired substitution associated with increased virulence of the influenza virus.

Download Full-text

In vitro characterization of multidrug-resistant influenza A(H1N1)pdm09 viruses carrying a dual amino acid substitution associated with reduced susceptibility to neuraminidase inhibitors

10.1101/334185 ◽

2018 ◽

Author(s):

Emi Takashita ◽

Seiichiro Fujisaki ◽

Masaru Yokoyama ◽

Masayuki Shirakura ◽

Kazuya Nakamura ◽

...

Keyword(s):

Amino Acid ◽

Amino Acid Substitution ◽

Influenza A ◽

Multidrug Resistant ◽

Cross Resistance ◽

Neuraminidase Inhibitors ◽

In Vitro Characterization ◽

Influenza A H1n1

AbstractWe detected influenza A(H1N1)pdm09 viruses carrying dual H275Y/I223R, H275Y/I223K, or H275Y/G147R substitutions in their neuraminidase protein, respectively. These viruses showed cross-resistance to oseltamivir and peramivir and reduced susceptibility to zanamivir. The H275Y/G147R virus retained its replication capability at least in vitro, but the H275Y/I223R and H275Y/I223K viruses did not.

Download Full-text

Contemporary Seasonal Influenza A (H1N1) Virus Infection Primes for a More Robust Response To Split Inactivated Pandemic Influenza A (H1N1) Virus Vaccination in Ferrets

Clinical and Vaccine Immunology ◽

10.1128/cvi.00247-10 ◽

2010 ◽

Vol 17 (12) ◽

pp. 1998-2006 ◽

Cited By ~ 11

Author(s):

Ali H. Ellebedy ◽

Thomas P. Fabrizio ◽

Ghazi Kayali ◽

Thomas H. Oguin ◽

Scott A. Brown ◽

...

Keyword(s):

Influenza Virus ◽

Pandemic Influenza ◽

Influenza A ◽

Seasonal Influenza ◽

H1n1 Virus ◽

H1n1 Influenza ◽

Influenza Viruses ◽

Inactivated Vaccine ◽

H1n1 Influenza Virus ◽

Influenza A H1n1

ABSTRACT Human influenza pandemics occur when influenza viruses to which the population has little or no immunity emerge and acquire the ability to achieve human-to-human transmission. In April 2009, cases of a novel H1N1 influenza virus in children in the southwestern United States were reported. It was retrospectively shown that these cases represented the spread of this virus from an ongoing outbreak in Mexico. The emergence of the pandemic led to a number of national vaccination programs. Surprisingly, early human clinical trial data have shown that a single dose of nonadjuvanted pandemic influenza A (H1N1) 2009 monovalent inactivated vaccine (pMIV) has led to a seroprotective response in a majority of individuals, despite earlier studies showing a lack of cross-reactivity between seasonal and pandemic H1N1 viruses. Here we show that previous exposure to a contemporary seasonal H1N1 influenza virus and to a lesser degree a seasonal influenza virus trivalent inactivated vaccine is able to prime for a higher antibody response after a subsequent dose of pMIV in ferrets. The more protective response was partially dependent on the presence of CD8+ cells. Two doses of pMIV were also able to induce a detectable antibody response that provided protection from subsequent challenge. These data show that previous infection with seasonal H1N1 influenza viruses likely explains the requirement for only a single dose of pMIV in adults and that vaccination campaigns with the current pandemic influenza vaccines should reduce viral burden and disease severity in humans.

Download Full-text

A single-amino-acid substitution in the HA protein changes the replication and pathogenicity of the 2009 pandemic A (H1N1) influenza viruses in vitro and in vivo

Virology Journal ◽

10.1186/1743-422x-7-325 ◽

2010 ◽

Vol 7 (1) ◽

pp. 325 ◽

Cited By ~ 27

Author(s):

Lili Xu ◽

Linlin Bao ◽

Qi Lv ◽

Wei Deng ◽

Yila Ma ◽

...

Keyword(s):

Amino Acid ◽

Amino Acid Substitution ◽

H1n1 Influenza ◽

Influenza Viruses ◽

Single Amino Acid Substitution ◽

Single Amino Acid ◽

Ha Protein

Download Full-text

Population immunity for influenza in population of Sverdlovsk Region in epidemic season of 2018–2019

Medical alphabet ◽

10.33667/2078-5631-2020-18-26-28 ◽

2020 ◽

pp. 26-28

Author(s):

I. A. Malchikov ◽

A. V. Slobodenyuk ◽

I. V. Vyalykh ◽

A. Yu. Markaran ◽

Yu. V. Grigorieva ◽

...

Keyword(s):

Influenza A ◽

Adult Population ◽

Laboratory Data ◽

Influenza Viruses ◽

H3n2 Virus ◽

Influenza B Virus ◽

Influenza B ◽

Epidemic Season ◽

Influenza A H1n1 ◽

Epidemic Period

Donor blood serum was tested to detect antibodies against circulating influenza viruses. The titer of specific antibodies was determined in the hemagglutination inhibition test (RTGA) against influenza viruses A/California/07/09(H1N1) pdm09, A/HongKong/4801/14(H3N2) and B/Brisben/46/15. In the pre-epidemic period 2018–2019, the immune layer of people with conditionally protective titers of antiviral antibodies was detected in terms of the lowest to A(H3N2) virus (50.0 %), the highest to influenza B (85.4 %). In the post-epidemic season of 2018–2019, the immune layer to influenza A(H1N1) pdm09 virus did not change significantly, which could indicate the preservation of the activity of this virus in the adult population; an increase in the immune layer of individuals with protective titers of antibodies to influenza A(H3N2) – 67.4 % and a decrease in influenza B virus – 49.2 %. A comparison of the results of laboratory data carried out in the pre- and post-epidemic seasons revealed significant differences in the number of people with average antibody titers against influenza A(H3N2) and B viruses (p < 0.05).

Download Full-text

Selenium Nanoparticles Inhibited H1N1 Influenza Virus Induced Apoptosis By Improving The Level of Gpx1

10.21203/rs.3.rs-1070042/v1 ◽

2021 ◽

Author(s):

Xia Liu ◽

Danyang Chen ◽

Jingyao Su ◽

Rulin Zheng ◽

Zhihui Ning ◽

...

Keyword(s):

Influenza A ◽

Mdck Cells ◽

Influenza Infection ◽

Chromatin Condensation ◽

H1n1 Influenza ◽

Influenza Viruses ◽

Selenium Nanoparticles ◽

Influenza A H1n1 ◽

Mechanistic Investigation ◽

Induced Apoptosis

Abstract Influenza A (H1N1) viruses are distributed around the world and pose a threat to public health. Vaccination is the main treatment strategy to prevent influenza infection, but antiviral drugs also play an important role in controlling seasonal and pandemic influenza. Currently, influenza viruses may emerge antiviral resistance, new agents with different modes of action are being investigated. Recently, selenium nanoparticles (SeNPs) which have antiviral effects attracted more and more attention in biomedical interventions. The appearance of nanotechnology attract great attention in the nanomedicine field. SeNPs constitute an attractive vector platform for delivering a variety of drugs to action targets. SeNPs is being explored for potential therapeutic efficacy in a variety of oxidative stress and inflammation-mediated diseases, such as cancer, arthritis, diabetes, and kidney disease. SeNPs could inhibit infection of Madin Darby Canine Kidney (MDCK) cells with H1N1 and prevent chromatin condensation and DNA fragmentation. ROS play a key role in physiological processes on apoptosis. SeNPs significantly inhibited the production of reactive oxygen species (ROS) in MDCK cells. Mechanistic investigation revealed that SeNPs inhibited the apoptosis induced by H1N1 virus infection in MDCK cells by improving the level of GPx1. Our results suggest that SeNPs is an effective selenium source to obtain H1N1 influenza antiviral candidate.

Download Full-text

The 2015-2016 epidemic season in Russia and the world: Circulation of influenza viruses, trends in incidence, clinical aspects, and treatment algorithm

Terapevticheskii arkhiv ◽

10.17116/terarkh20168811112-120 ◽

2016 ◽

Vol 88 (11) ◽

pp. 112-120 ◽

Cited By ~ 1

Author(s):

D K Lvov ◽

L V Kolobukhina ◽

E I Burtseva ◽

I S Kruzhkova ◽

N A Malyshev ◽

...

Keyword(s):

Pregnant Women ◽

Russian Federation ◽

Influenza A ◽

Influenza Viruses ◽

Research Centre ◽

Clinical Aspects ◽

Ministry Of Health ◽

Epidemic Season ◽

Influenza A H1n1 ◽

The Russian Federation

In the 2015—2016 epidemic season, there were dominant influenza A(H1N1)pdm09 strains (over 90%) among the circulating influenza viruses in most countries of the Northern Hemisphere and in Russia. A study of the antigenic properties of influenza A(H1N1)pdm09 strains revealed no differences in those of vaccine virus. Sequencing showed that there were amino acid substitutions in hemagglutinin (receptor binding and Sa sites) and in the genes encoding internal proteins (PA, NP, M1, and NS1). The rise in the incidence in the Russian Federation, which was etiologically associated with influenza viruses, was registered in January-February 2016 with its maximum being observed at 4—5 weeks of 2016. Within the framework of the epidemiological surveillance of circulating influenza viruses in the Russian Federation, which was conducted by the WHO European Office, the D.I. Ivanovsky Institute of Virology, Honorary Academician N.F. Gamaleya Federal Research Centre for Epidemiology and Microbiology, Ministry of Health of Russia, and the Research Institute of Influenza, Ministry of Health of Russia, monitored at the Infectious Diseases Hospital One (IDH-1), Moscow Healthcare Department. Among 1491 examinees, influenza was verified in 104 (21.3%) adults, 208 (42.5%) pregnant women, and 177 (36.2%) children. Influenza A(H1N1)pdm09 was more often diagnosed in the age group of 15—40 years (63.7%); the proportion of influenza patients aged over 50 years increased (22.1%). Most adult patients had moderate influenza; pneumonia complicated the disease in 27.4%. Influenza in the pregnant women was complicated by pneumonia in 4.8% of cases. Influenza was more frequently diagnosed in infants and preschool children aged 0 to 3 years (42.9%), 4 to 6 years (41.2%), and older (15.9%), namely: 7—9 years (10%) and 10—12 years (5.9%). Influenza in the children was complicated by acute tonsillitis (19.4%) and varying degrees of laryngeal stenosis (12.4%). Bronchial obstructive syndrome developed in 2.5%, the rate of pneumonia was 6.2%. Antiviral therapy (AVT) in the early stages of the disease reduces the risk of its severity, the frequency of secondary complications, and the duration and degree of clinical symptoms of influenza. AVT with oseltamivir, zanamivir, imidazolyl ethanamide pentandioic acid (ingavirin), and interferon-a2b (viferon) has been performed in the patients hospitalized at Moscow IDH-1 in the 2015—2016 epidemic season.

Download Full-text

Influenza viruses resistant to neuraminidase inhibitors.

Acta Biochimica Polonica ◽

10.18388/abp.2014_1871 ◽

2014 ◽

Vol 61 (3) ◽

Cited By ~ 16

Author(s):

Aneta Nitsch-Osuch ◽

Lidia Bernadeta Brydak

Keyword(s):

Influenza A ◽

Seasonal Influenza ◽

Influenza Viruses ◽

Response To Treatment ◽

Cross Resistance ◽

Published Data ◽

Neuraminidase Inhibitors ◽

Viral Particles ◽

Clinical Resistance ◽

Influenza A H1n1

Neuraminidase inhibitors (NAIs) are antiviral drugs for treatment and prophylaxis of influenza. By blocking the activity of the enzyme neuraminidase, NAIs prevent new viral particles from being released. The increasing use of NAIs brings into focus the risk of drug resistance arising to the class. There are three levels of antiviral resistance according to the way that resistance can be detected or inferred: genotypic, phenotypic and clinical resistance. For many years seasonal influenza viruses resistance to NAIs was low (0.33%). Recently, there has been described an increasing number of resistant seasonal influenza strains to oseltamivir (2% in adults, 5-18% in children). In 2007 there were published data describing 14% resistant to oseltamivir strains of influenza A/H1N1/ in Europe. Approximately 0.5-1.0% of influenza A/H1N1/pdm09 isolates are currently resistant to oseltamivir. The established markers of the resistance to oseltamivir were found in 2.4% of human and 0.8% of avian isolates of influenza A/H5N1/. It has been not observed a cross resistance among oseltamivir and zanamivir. NAIs resistance in influenza viruses is relative and despite its presence patients with resistant viruses may still benefit from receiving these antivirals. The response to treatment with antivirals remains the most important proof of antiviral effectiveness. The rational use of NAIs is essential to preserve the best choice for treatment and prophylaxis of seasonal, avian and pandemic influenza.

Download Full-text

Analysis of influenza A virus reinfection in children in Japan during 1983–91

Epidemiology and Infection ◽

10.1017/s0950268800058751 ◽

1995 ◽

Vol 115 (3) ◽

pp. 591-601 ◽

Cited By ~ 5

Author(s):

S. Nakajima ◽

F. Nishikawa ◽

K. Nakamura ◽

K. Nakajima

Keyword(s):

Amino Acid ◽

Influenza A Virus ◽

Influenza A ◽

Haemagglutination Inhibition ◽

Influenza Viruses ◽

Antigenic Drift ◽

H3n2 Virus ◽

Influenza B ◽

Influenza A H1n1 ◽

Influenza H3n2

SummaryThe epidemiology of influenza A in Japan was studied during 1979–91 and viruses isolated from reinfections during 1983–91 were analysed, Of 2963 influenza viruses isolated during this period, 922 and 1006 were influenza A(H1N1) and A(H3N2) viruses respectively; the others were influenza B viruses. Influenza A(H1N1) and A(H3N2) caused 5 and 6 epidemics respectively, most accompanied by antigenic drift. Seventeen reinfections with H1N1 and 17 with H3N2 were detected during our study. The primary and reinfection strains isolated from 7 H1N1 and 10 H3N2 cases were studied by haemagglutination-inhibition, and amino acid and nucleotide sequences of the HA1 region of the haemagglutinin. Most of the primary and reinfection strains were antigenically and genetically similar to the epidemic viruses circulating at that time. However, in 4 out of 10 cases of reinfection with influenza H3N2 virus, reinfection strains were genetically different from the epidemic viruses.

Download Full-text