Amino acid substitution D222N from fatal influenza infection affects receptor-binding properties of the influenza A(H1N1)pdm09 virus

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.

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Molecular characterization of influenza A(H1N1)pdm09 virus circulating during the 2009 outbreak in Thua Thien Hue, Vietnam

The Journal of Infection in Developing Countries ◽

10.3855/jidc.2883 ◽

2013 ◽

Vol 7 (03) ◽

pp. 235-242 ◽

Cited By ~ 3

Author(s):

Le Van An ◽

Le Thi Bao Chi ◽

Nguyen Hoang Bach ◽

Huynh Thi Hai Duong ◽

Massimo Deligios ◽

...

Keyword(s):

Amino Acid ◽

Influenza A ◽

The United States ◽

Rt Pcr ◽

Viral Isolation ◽

Pdm09 Virus ◽

Influenza A H1n1 ◽

Virus Culture ◽

Na Sequences ◽

Viral Diagnosis

Introduction: The influenza A(H1N1)pdm09 virus arrived in Vietnam in May 2009 via the United States and rapidly spread throughout the country. This study provides data on the viral diagnosis and molecular epidemiology of influenza A(H1N1)pdm09 virus isolated in Thua Thien Hue Province, central Vietnam. Methodology: Nasopharyngeal swabs and throat swabs from 53 clinically infected patients in the peak of the outbreak were processed for viral diagnosis by culture and RT-PCR. Sequencing of entire HA and NA genes of representative isolates and molecular epidemiological analysis were performed. Results: A total of 32 patients were positive for influenza A virus by virus culture and/or RT-PCR; of these 22 were positive both by viral isolation and RT-PCR, 2 only by virus culture and 8 only by RT-PCR. The novel subtype of influenza A(H1N1)pdm09 was present in 93.4% of the isolates. Phylogenetic analysis of the HA and NA gene sequences showed identities higher than 99.50% in both genes. They were also similar to reference isolates in HA sequences (> 99% identity) and in NA sequences (>98.50% identity). Amino acid sequences predicted for the HA gene were highly identical to reference strains. The NA amino acid substitutions identified did not include the oseltamivir-resistant H275Y substitution. Conclusion: viral isolation and RT-PCR together were useful for diagnosis of the influenza A(H1N1)pdm09 virus. Variations in HA and NA sequences are similar to those identified in worldwide reference isolates and no drug resistance was found.

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Identification of Amino Acid Substitutions Supporting Antigenic Change of Influenza A(H1N1)pdm09 Viruses

Journal of Virology ◽

10.1128/jvi.02962-14 ◽

2015 ◽

Vol 89 (7) ◽

pp. 3763-3775 ◽

Cited By ~ 50

Author(s):

Björn F. Koel ◽

Ramona Mögling ◽

Salin Chutinimitkul ◽

Pieter L. Fraaij ◽

David F. Burke ◽

...

Keyword(s):

Amino Acid ◽

Receptor Binding ◽

Influenza A ◽

Influenza Pandemic ◽

Amino Acid Substitutions ◽

Receptor Binding Site ◽

Population Immunity ◽

Influenza A H1n1 ◽

Hemagglutinin Protein ◽

2009 Influenza Pandemic

ABSTRACTThe majority of currently circulating influenza A(H1N1) viruses are antigenically similar to the virus that caused the 2009 influenza pandemic. However, antigenic variants are expected to emerge as population immunity increases. Amino acid substitutions in the hemagglutinin protein can result in escape from neutralizing antibodies, affect viral fitness, and change receptor preference. In this study, we constructed mutants with substitutions in the hemagglutinin of A/Netherlands/602/09 in an attenuated backbone to explore amino acid changes that may contribute to emergence of antigenic variants in the human population. Our analysis revealed that single substitutions affecting the loop that consists of amino acid positions 151 to 159 located adjacent to the receptor binding site caused escape from ferret and human antibodies elicited after primary A(H1N1)pdm09 virus infection. The majority of these substitutions resulted in similar or increased replication efficiencyin vitrocompared to that of the virus carrying the wild-type hemagglutinin and did not result in a change of receptor preference. However, none of the substitutions was sufficient for escape from the antibodies in sera from individuals that experienced both seasonal and pandemic A(H1N1) virus infections. These results suggest that antibodies directed against epitopes on seasonal A(H1N1) viruses contribute to neutralization of A(H1N1)pdm09 antigenic variants, thereby limiting the number of possible substitutions that could lead to escape from population immunity.IMPORTANCEInfluenza A viruses can cause significant morbidity and mortality in humans. Amino acid substitutions in the hemagglutinin protein can result in escape from antibody-mediated neutralization. This allows the virus to reinfect individuals that have acquired immunity to previously circulating strains through infection or vaccination. To date, the vast majority of A(H1N1)pdm09 strains remain antigenically similar to the virus that caused the 2009 influenza pandemic. However, antigenic variants are expected to emerge as a result of increasing population immunity. We show that single amino acid substitutions near the receptor binding site were sufficient to escape from antibodies specific for A(H1N1)pdm09 viruses but not from antibodies elicited in response to infections with seasonal A(H1N1) and A(H1N1)pdm09 viruses. This study identified substitutions in A(H1N1)pdm09 viruses that support escape from population immunity but also suggested that the number of potential escape variants is limited by previous exposure to seasonal A(H1N1) viruses.

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SALIENT FEATURES OF CIRCULATING RESPIRATORY VIRUSES IN THE PRE– AND PANDEMIC INFLUENZA AND COVID–19 SEASONS

Russian Journal of Infection and Immunity ◽

10.15789/2220-7619-sfo-1662 ◽

2021 ◽

Author(s):

I. V. Kiseleva ◽

N. V. Larionova ◽

E. P. Grigorieva ◽

A. D. Ksenafontov ◽

M. Al Farroukh ◽

...

Keyword(s):

Pandemic Influenza ◽

Influenza A ◽

Influenza Infection ◽

Opportunity To Learn ◽

Respiratory Viruses ◽

Influenza Viruses ◽

Effective Prevention ◽

Pdm09 Virus ◽

Influenza A H1n1 ◽

Syncytial Virus

Abstract. A wide variety of zoonotic viruses that can cross the interspecies barrier promote the emergence of new, potentially pandemic viruses in the human population that was often accompanied by the disappearance of existing circulating strains. Among the various reasons underlying this phenomenon is the strengthening of populational immunity by expanding the immune layer of the population and improving the means and methods of medical care. However, “Natura abhorret vacuum”, and new pathogens come to replace disappearing pathogens. In the past ten years, there have been two critical events – the pandemic spread of the swine influenza A (H1N1) pdm09 virus in 2009 and the novel SARS–CoV–2 coronavirus in 2019, providing scientists with a unique opportunity to learn more about a relationship between respiratory viruses and their pathogenesis. Together with viruses of pandemic significance, a large number of seasonal respiratory viruses circulate, which contribute to the structure of human morbidity, and co–infections aggravate the condition of the illness. In the conditions of the spread of new viruses with unexplored characteristics, in the absence of means of prevention and therapy, it is especially important to prevent the aggravation of morbidity due to mixed infections. Here we review the mutual involvement of pandemic influenza A(H1N1)pdm09 and SARS–CoV–2 coronavirus and seasonal respiratory viruses in the epidemic process, discuss some issues related to their spread, potential causes affecting the spread and severity of the morbidity. The given facts, testify to the existence of seasonality and temporal patterns of the beginning and end of the circulation of respiratory viruses. Interestingly, the beginning of the circulation of the pandemic influenza A(H1N1)pdm09 virus led to a shift in the timing and intensity of circulation of some respiratory viruses, which is probably caused by the existence of "replication conflicts" between them, and did not affect others. Co–infection with SARS–CoV–2–19 and other respiratory viruses, especially respiratory syncytial virus and rhinoviruses, was quite often observed. At the current stage, no aggravating effect of influenza on the course of COVID–19 in mixed infection has been established. Whether this is due to the mild course of influenza infection in the 2020 epidemic season, or the competitive impact of SARS–CoV–2 on influenza viruses is not yet clear. Experts are still at the stage of accumulating facts and working on creating means of effective prevention and treatment of the new coronavirus infection.

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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.

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