Evolution of the NS genes of the influenza a viruses. II. Characteristics of the amino acid changes in the NS1 proteins of the influenza a viruses

Virus Genes ◽  
1990 ◽  
Vol 4 (1) ◽  
pp. 15-26 ◽  
Author(s):  
Katsuhisa Nakajima ◽  
Eri Nobusawa ◽  
Setsuko Nakajima
Keyword(s):  
Amino Acid ◽  
Influenza A ◽  
Influenza A Viruses

scholarly journals Characterization of H9N2 influenza A viruses isolated from chicken products imported into Japan from China

2006 ◽  
Vol 135 (3) ◽  
pp. 386-391 ◽  
Author(s):  
M. MASE ◽  
M. ETO ◽  
K. IMAI ◽  
K. TSUKAMOTO ◽  
S. YAMAGUCHI
Keyword(s):  
Influenza Virus ◽  
Amino Acid ◽  
Avian Influenza ◽  
Avian Influenza Virus ◽  
Influenza A ◽  
H9n2 Virus ◽  
Amino Acid Substitutions ◽  
Influenza A Viruses ◽  
Potential Sources

We characterized eleven H9N2 influenza A viruses isolated from chicken products imported from China. Genetically they were classified into six distinct genotypes, including five already known genotypes and one novel genotype. This suggested that such multiple genotypes of the H9N2 virus have possibly already become widespread and endemic in China. Two isolates have amino-acid substitutions that confer resistance to amantadine in the M2 region, and this supported the evidence that this mutation might be a result of the wide application of amantadine for avian influenza treatment in China. These findings emphasize the importance of surveillance for avian influenza virus in this region, and of quarantining imported chicken products as potential sources for the introduction of influenza virus.

scholarly journals Plasticity of the Influenza Virus H5 HA Protein

mBio ◽  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Huihui Kong ◽  
David F. Burke ◽  
Tiago Jose da Silva Lopes ◽  
Kosuke Takada ◽  
Masaki Imai ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Amino Acid ◽  
Mammalian Cells ◽  
Influenza A ◽  
Viral Antigen ◽  
Influenza Viruses ◽  
Influenza A Viruses ◽  
Highly Pathogenic ◽  
Antigenic Properties ◽  
Ha Protein

ABSTRACT Since the emergence of highly pathogenic avian influenza viruses of the H5 subtype, the major viral antigen, hemagglutinin (HA), has undergone constant evolution, resulting in numerous genetic and antigenic (sub)clades. To explore the consequences of amino acid changes at sites that may affect the antigenicity of H5 viruses, we simultaneously mutated 17 amino acid positions of an H5 HA by using a synthetic gene library that, theoretically, encodes all combinations of the 20 amino acids at the 17 positions. All 251 mutant viruses sequenced possessed ≥13 amino acid substitutions in HA, demonstrating that the targeted sites can accommodate a substantial number of mutations. Selection with ferret sera raised against H5 viruses of different clades resulted in the isolation of 39 genotypes. Further analysis of seven variants demonstrated that they were antigenically different from the parental virus and replicated efficiently in mammalian cells. Our data demonstrate the substantial plasticity of the influenza virus H5 HA protein, which may lead to novel antigenic variants. IMPORTANCE The HA protein of influenza A viruses is the major viral antigen. In this study, we simultaneously introduced mutations at 17 amino acid positions of an H5 HA expected to affect antigenicity. Viruses with ≥13 amino acid changes in HA were viable, and some had altered antigenic properties. H5 HA can therefore accommodate many mutations in regions that affect antigenicity. The substantial plasticity of H5 HA may facilitate the emergence of novel antigenic variants.

scholarly journals Genetic and Antigenic Evolution of European Swine Influenza A Viruses of HA-1C (Avian-Like) and HA-1B (Human-Like) Lineages in France from 2000 to 2018

Viruses ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1304
Author(s):  
Amélie Chastagner ◽  
Séverine Hervé ◽  
Stéphane Quéguiner ◽  
Edouard Hirchaud ◽  
Pierrick Lucas ◽  
...  
Keyword(s):  
Amino Acid ◽  
Influenza A ◽  
Phylogenetic Analyses ◽  
Swine Influenza ◽  
Amino Acid Sequences ◽  
Antigenic Drift ◽  
Influenza A Viruses ◽  
Double Deletion ◽  
Antigenic Evolution ◽  
Amino Acid Mutations

This study evaluated the genetic and antigenic evolution of swine influenza A viruses (swIAV) of the two main enzootic H1 lineages, i.e., HA-1C (H1av) and -1B (H1hu), circulating in France between 2000 and 2018. SwIAV RNAs extracted from 1220 swine nasal swabs were hemagglutinin/neuraminidase (HA/NA) subtyped by RT-qPCRs, and 293 virus isolates were sequenced. In addition, 146 H1avNy and 105 H1huNy strains were submitted to hemagglutination inhibition tests. H1avN1 (66.5%) and H1huN2 (25.4%) subtypes were predominant. Most H1 strains belonged to HA-1C.2.1 or -1B.1.2.3 clades, but HA-1C.2, -1C.2.2, -1C.2.3, -1B.1.1, and -1B.1.2.1 clades were also detected sporadically. Within HA-1B.1.2.3 clade, a group of strains named “Δ146-147” harbored several amino acid mutations and a double deletion in HA, that led to a marked antigenic drift. Phylogenetic analyses revealed that internal segments belonged mainly to the “Eurasian avian-like lineage”, with two distinct genogroups for the M segment. In total, 17 distinct genotypes were identified within the study period. Reassortments of H1av/H1hu strains with H1N1pdm virus were rarely evidenced until 2018. Analysis of amino acid sequences predicted a variability in length of PB1-F2 and PA-X proteins and identified the appearance of several mutations in PB1, PB1-F2, PA, NP and NS1 proteins that could be linked to virulence, while markers for antiviral resistance were identified in N1 and N2. Altogether, diversity and evolution of swIAV recall the importance of disrupting the spreading of swIAV within and between pig herds, as well as IAV inter-species transmissions.

scholarly journals Duck Interferon-Inducible Transmembrane Protein 3 Mediates Restriction of Influenza Viruses

2015 ◽  
Vol 90 (1) ◽  
pp. 103-116 ◽  
Author(s):  
Graham A. D. Blyth ◽  
Wing Fuk Chan ◽  
Robert G. Webster ◽  
Katharine E. Magor
Keyword(s):  
Influenza Virus ◽  
Amino Acid ◽  
Avian Influenza ◽  
Influenza A ◽  
Natural Host ◽  
Endocytic Pathway ◽  
Influenza A Viruses ◽  
Highly Pathogenic ◽  
Terminal Domain ◽  
Antiviral Function

ABSTRACTInterferon-inducible transmembrane proteins (IFITMs) can restrict the entry of a wide range of viruses. IFITM3 localizes to endosomes and can potently restrict the replication of influenza A viruses (IAV) and several other viruses that also enter host cells through the endocytic pathway. Here, we investigate whether IFITMs are involved in protection in ducks, the natural host of influenza virus. We identify and sequence duckIFITM1,IFITM2,IFITM3, andIFITM5. Using quantitative PCR (qPCR), we demonstrate the upregulation of these genes in lung tissue in response to highly pathogenic IAV infection by 400-fold, 30-fold, 30-fold, and 5-fold, respectively. We express each IFITM in chicken DF-1 cells and show duck IFITM1 localizes to the cell surface, while IFITM3 localizes to LAMP1-containing compartments. DF-1 cells stably expressing duck IFITM3 (but not IFITM1 or IFITM2) show increased restriction of replication of H1N1, H6N2, and H11N9 IAV strains but not vesicular stomatitis virus. Although duck and human IFITM3 share only 38% identity, critical residues for viral restriction are conserved. We generate chimeric and mutant IFITM3 proteins and show duck IFITM3 does not require its N-terminal domain for endosomal localization or antiviral function; however, this N-terminal end confers endosomal localization and antiviral function on IFITM1. In contrast to mammalian IFITM3, the conserved YXXθ endocytosis signal sequence in the N-terminal domain of duck IFITM3 is not essential for correct endosomal localization. Despite significant structural and amino acid divergence, presumably due to host-virus coevolution, duck IFITM3 is functional against IAV.IMPORTANCEImmune IFITM genes are poorly conserved across species, suggesting that selective pressure from host-specific viruses has driven this divergence. We wondered whether coevolution between viruses and their natural host would result in the evasion of IFITM restriction. Ducks are the natural host of avian influenza A viruses and display few or no disease symptoms upon infection with most strains, including highly pathogenic avian influenza. We have characterized the duck IFITM locus and identified IFITM3 as an important restrictor of several influenza A viruses, including avian strains. With only 38% amino acid identity to human IFITM3, duck IFITM3 possesses antiviral function against influenza virus. Thus, despite long coevolution of virus and host effectors in the natural host, influenza virus evasion of IFITM3 restriction in ducks is not apparent.

scholarly journals Natural Selection of H5N1 Avian Influenza A Viruses with Increased PA-X and NS1 Shutoff Activity

Viruses ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1760
Author(s):  
Aitor Nogales ◽  
Laura Villamayor ◽  
Sergio Utrilla-Trigo ◽  
Javier Ortego ◽  
Luis Martinez-Sobrido ◽  
...  
Keyword(s):  
Amino Acid ◽  
Virulence Factors ◽  
Influenza A ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Influenza A Viruses ◽  
Antiviral Responses ◽  
H5n1 Avian Influenza ◽  
Inhibit Gene Expression ◽  
Important Challenge

Influenza A viruses (IAV) can infect a broad range of mammalian and avian species. However, the host innate immune system provides defenses that restrict IAV replication and infection. Likewise, IAV have evolved to develop efficient mechanisms to counteract host antiviral responses to efficiently replicate in their hosts. The IAV PA-X and NS1 non-structural proteins are key virulence factors that modulate innate immune responses and virus pathogenicity during infection. To study the determinants of IAV pathogenicity and their functional co-evolution, we evaluated amino acid differences in the PA-X and NS1 proteins of early (1996–1997) and more recent (since 2016) H5N1 IAV. H5N1 IAV have zoonotic and pandemic potential and represent an important challenge both in poultry farming and human health. The results indicate that amino acid changes occurred over time, affecting the ability of these two non-structural H5N1 IAV proteins to inhibit gene expression and affecting virus pathogenicity. These results highlight the importance to monitor the evolution of these two virulence factors of IAV, which could result in enhanced viral replication and virulence.

scholarly journals FluPhenotype—a one-stop platform for early warnings of the influenza A virus

2020 ◽  
Vol 36 (10) ◽  
pp. 3251-3253 ◽  
Author(s):  
Congyu Lu ◽  
Zena Cai ◽  
Yuanqiang Zou ◽  
Zheng Zhang ◽  
Wenjun Chen ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Amino Acid ◽  
Influenza A ◽  
Genetic Relationships ◽  
Influenza Viruses ◽  
Supplementary Information ◽  
Influenza A Viruses ◽  
One Stop ◽  
Related Amino Acid ◽  
Early Warnings

Abstract Motivation Newly emerging influenza viruses keep challenging global public health. To evaluate the potential risk of the viruses, it is critical to rapidly determine the phenotypes of the viruses, including the antigenicity, host, virulence and drug resistance. Results Here, we built FluPhenotype, a one-stop platform to rapidly determinate the phenotypes of the influenza A viruses. The input of FluPhenotype is the complete or partial genomic/protein sequences of the influenza A viruses. The output presents five types of information about the viruses: (i) sequence annotation including the gene and protein names as well as the open reading frames, (ii) potential hosts and human-adaptation-associated amino acid markers, (iii) antigenic and genetic relationships with the vaccine strains of different HA subtypes, (iv) mammalian virulence-related amino acid markers and (v) drug resistance-related amino acid markers. FluPhenotype will be a useful bioinformatic tool for surveillance and early warnings of the newly emerging influenza A viruses. Availability and implementation It is publicly available from: http://www.computationalbiology.cn : 18888/IVEW. Supplementary information Supplementary data are available at Bioinformatics online.

Optimization of M2e cassette amino acid composition for the development of universal influenza vaccine

2021 ◽  
Vol 21 (3) ◽  
pp. 127-130
Author(s):  
Daria А. Mezhenskaya ◽  
Irina N. Isakova-Sivak ◽  
Anastasiya E. Katelnikova ◽  
Larisa G. Rudenko
Keyword(s):  
Public Health ◽  
Amino Acid ◽  
Influenza Vaccine ◽  
Influenza A ◽  
Wide Spectrum ◽  
Qualitative Assessment ◽  
Influenza A Viruses ◽  
Duration Of Action ◽  
Natural Reservoir ◽  
Universal Influenza Vaccine

The development of a universal influenza vaccine with a wide spectrum and duration of action is one of the serious public health problems. This study is dedicated to optimization of an immunogen covering the M2e epitopes of influenza A viruses circulating in the natural reservoir, as well as the creation of a prototype of a universal influenza vaccine with subsequent quantitative and qualitative assessment of the induced anti-M2e responses in ferrets.

scholarly journals Replicative Fitness of Seasonal Influenza A Viruses With Decreased Susceptibility to Baloxavir

2019 ◽  
Author(s):  
Anton Chesnokov ◽  
Mira C Patel ◽  
Vasiliy P Mishin ◽  
Juan A De La Cruz ◽  
Lori Lollis ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Amino Acid ◽  
Amino Acid Residue ◽  
Differential Effect ◽  
Influenza A ◽  
Seasonal Influenza ◽  
Influenza A Viruses ◽  
Replicative Fitness ◽  
Model Control

Abstract Susceptibility of influenza A viruses to baloxavir can be affected by changes at amino acid residue 38 in the polymerase acidic (PA) protein. Information on replicative fitness of PA-I38-substituted viruses remains sparse. We demonstrated that substitutions I38L/M/S/T not only had a differential effect on baloxavir susceptibility (9- to 116-fold) but also on in vitro replicative fitness. Although I38L conferred undiminished growth, other substitutions led to mild attenuation. In a ferret model, control viruses outcompeted those carrying I38M or I38T substitutions, although their advantage was limited. These findings offer insights into the attributes of baloxavir-resistant viruses needed for informed risk assessment.

scholarly journals NS1 Protein Amino Acid Changes D189N and V194I Affect Interferon Responses, Thermosensitivity, and Virulence of Circulating H3N2 Human Influenza A Viruses

2016 ◽  
Vol 91 (5) ◽  
Author(s):  
Aitor Nogales ◽  
Luis Martinez-Sobrido ◽  
David J. Topham ◽  
Marta L. DeDiego
Keyword(s):  
Influenza Virus ◽  
Amino Acid ◽  
Immune Responses ◽  
Influenza A ◽  
Innate Immune ◽  
Temperature Sensitive ◽  
Ns1 Protein ◽  
Innate Immune Responses ◽  
Influenza A Viruses ◽  
Virus Surveillance

ABSTRACT Influenza virus NS1 protein is a nonstructural, multifunctional protein that counteracts host innate immune responses, modulating virus pathogenesis. NS1 protein variability in subjects infected with H3N2 influenza A viruses (IAVs) during the 2010/2011 season was analyzed, and amino acid changes in residues 86, 189, and 194 were found. The consequences of these mutations for the NS1-mediated inhibition of IFN responses and the pathogenesis of the virus were evaluated, showing that NS1 mutations D189N and V194I impaired the ability of the NS1 protein to inhibit general gene expression, most probably because these mutations decreased the binding of NS1 to the cleavage and polyadenylation specificity factor 30 (CPSF30). A recombinant A/Puerto Rico/8/34 (PR8) H1N1 virus encoding the H3N2 NS1-D189N protein was slightly attenuated, whereas the virus encoding the H3N2 NS1-V194I protein was further attenuated in mice. The higher attenuation of this virus could not be explained by differences in the ability of the two NS1 proteins to counteract host innate immune responses, indicating that another factor must be responsible. In fact, we showed that the virus encoding the H3N2 NS1-V194I protein demonstrated a temperature-sensitive (ts) phenotype, providing a most likely explanation for the stronger attenuation observed. As far as we know, this is the first description of a mutation in NS1 residue 194 conferring a ts phenotype. These studies are relevant in order to identify new residues important for NS1 functions and in human influenza virus surveillance to assess mutations affecting the pathogenicity of circulating viruses. IMPORTANCE Influenza viral infections represent a serious public health problem, with influenza virus causing a contagious respiratory disease that is most effectively prevented through vaccination. The multifunctional nonstructural protein 1 (NS1) is the main viral factor counteracting the host antiviral response. Therefore, influenza virus surveillance to identify new mutations in the NS1 protein affecting the pathogenicity of the circulating viruses is highly important. In this work, we evaluated amino acid variability in the NS1 proteins from H3N2 human seasonal viruses and the effect of the mutations on innate immune responses and virus pathogenesis. NS1 mutations D189N and V194I impaired the ability of the NS1 protein to inhibit general gene expression, and recombinant viruses harboring these mutations were attenuated in a mouse model of influenza infection. Interestingly, a virus encoding the H3N2 NS1-V194I protein demonstrated a temperature-sensitive phenotype, further attenuating the virus in vivo.

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