scholarly journals Comparative Analysis of Evolutionary Mechanisms of the Hemagglutinin and Three Internal Protein Genes of Influenza B Virus: Multiple Cocirculating Lineages and Frequent Reassortment of the NP, M, and NS Genes

1999 ◽  
Vol 73 (5) ◽  
pp. 4413-4426 ◽  
Author(s):  
Stephen E. Lindstrom ◽  
Yasuaki Hiromoto ◽  
Hidekazu Nishimura ◽  
Takehiko Saito ◽  
Reiko Nerome ◽  
...  
Keyword(s):  
Amino Acid ◽  
Influenza A ◽  
Amino Acid Sequences ◽  
Evolutionary Rates ◽  
Influenza B Virus ◽  
Influenza B ◽  
Evolutionary Analysis ◽  
Human Influenza ◽  
Evolutionary Mechanisms ◽  
Ha Protein

ABSTRACT Phylogenetic profiles of the genes coding for the hemagglutinin (HA) protein, nucleoprotein (NP), matrix (M) protein, and nonstructural (NS) proteins of influenza B viruses isolated from 1940 to 1998 were analyzed in a parallel manner in order to understand the evolutionary mechanisms of these viruses. Unlike human influenza A (H3N2) viruses, the evolutionary pathways of all four genes of recent influenza B viruses revealed similar patterns of genetic divergence into two major lineages. Although evolutionary rates of the HA, NP, M, and NS genes of influenza B viruses were estimated to be generally lower than those of human influenza A viruses, genes of influenza B viruses demonstrated complex phylogenetic patterns, indicating alternative mechanisms for generation of virus variability. Topologies of the evolutionary trees of each gene were determined to be quite distinct from one another, showing that these genes were evolving in an independent manner. Furthermore, variable topologies were apparently the result of frequent genetic exchange among cocirculating epidemic viruses. Evolutionary analysis done in the present study provided further evidence for cocirculation of multiple lineages as well as sequestering and reemergence of phylogenetic lineages of the internal genes. In addition, comparison of deduced amino acid sequences revealed a novel amino acid deletion in the HA1 domain of the HA protein of recent isolates from 1998 belonging to the B/Yamagata/16/88-like lineage. It thus became apparent that, despite lower evolutionary rates, influenza B viruses were able to generate genetic diversity among circulating viruses through a combination of evolutionary mechanisms involving cocirculating lineages and genetic reassortment by which new variants with distinct gene constellations emerged.

scholarly journals Molecular Characterization of Seasonal Influenza A and B from Hospitalized Patients in Thailand in 2018–2019

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 977
Author(s):  
Kobporn Boonnak ◽  
Chayasin Mansanguan ◽  
Dennis Schuerch ◽  
Usa Boonyuen ◽  
Hatairat Lerdsamran ◽  
...  
Keyword(s):  
Amino Acid ◽  
Influenza A ◽  
Seasonal Influenza ◽  
Influenza Viruses ◽  
Surface Proteins ◽  
Antigenic Drift ◽  
Influenza B ◽  
Receptor Binding Site ◽  
Antigenic Sites ◽  
Ha Protein

Influenza viruses continue to be a major public health threat due to the possible emergence of more virulent influenza virus strains resulting from dynamic changes in virus adaptability, consequent of functional mutations and antigenic drift in surface proteins, especially hemagglutinin (HA) and neuraminidase (NA). In this study, we describe the genetic and evolutionary characteristics of H1N1, H3N2, and influenza B strains detected in severe cases of seasonal influenza in Thailand from 2018 to 2019. We genetically characterized seven A/H1N1 isolates, seven A/H3N2 isolates, and six influenza B isolates. Five of the seven A/H1N1 viruses were found to belong to clade 6B.1 and were antigenically similar to A/Switzerland/3330/2017 (H1N1), whereas two isolates belonged to clade 6B.1A1 and clustered with A/Brisbane/02/2018 (H1N1). Interestingly, we observed additional mutations at antigenic sites (S91R, S181T, T202I) as well as a unique mutation at a receptor binding site (S200P). Three-dimensional (3D) protein structure analysis of hemagglutinin protein reveals that this unique mutation may lead to the altered binding of the HA protein to a sialic acid receptor. A/H3N2 isolates were found to belong to clade 3C.2a2 and 3C.2a1b, clustering with A/Switzerland/8060/2017 (H3N2) and A/South Australia/34/2019 (H3N2), respectively. Amino acid sequence analysis revealed 10 mutations at antigenic sites including T144A/I, T151K, Q213R, S214P, T176K, D69N, Q277R, N137K, N187K, and E78K/G. All influenza B isolates in this study belong to the Victoria lineage. Five out of six isolates belong to clade 1A3-DEL, which relate closely to B/Washington/02/2009, with one isolate lacking the three amino acid deletion on the HA segment at position K162, N163, and D164. In comparison to the B/Colorado/06/2017, which is the representative of influenza B Victoria lineage vaccine strain, these substitutions include G129D, G133R, K136E, and V180R for HA protein. Importantly, the susceptibility to oseltamivir of influenza B isolates, but not A/H1N1 and A/H3N2 isolates, were reduced as assessed by the phenotypic assay. This study demonstrates the importance of monitoring genetic variation in influenza viruses regarding how acquired mutations could be associated with an improved adaptability for efficient transmission.

scholarly journals Antigenic variants with amino acid deletions clarify a neutralizing epitope specific for influenza B virus Victoria group strains

2001 ◽  
Vol 82 (9) ◽  
pp. 2169-2172 ◽  
Author(s):  
Naoko Nakagawa ◽  
Ritsuko Kubota ◽  
Toshimasa Nakagawa ◽  
Yoshinobu Okuno
Keyword(s):  
Amino Acid ◽  
Amino Acid Substitution ◽  
Haemagglutination Inhibition ◽  
Three Dimensional ◽  
Amino Acid Sequences ◽  
Single Amino Acid Substitution ◽  
Single Amino Acid ◽  
Influenza B Virus ◽  
Influenza B ◽  
B Virus

To study the neutralizing epitopes of influenza B virus Victoria group strains, two monoclonal antibodies (MAbs) were used to select antigenic variants of the virus. MAbs 10B8 and 8E6 were found to react with B/Victoria group strains in three tests, peroxidase–antiperoxidase staining, haemagglutination inhibition and neutralization tests; no reactivity with B/Yamagata group strains was observed. Analysis of the deduced amino acid sequences of 10B8-induced variants identified a single amino acid deletion at residue 165 or 170, as well as a single amino acid substitution at residues 164 (Asp→Tyr), 165 (Asn→Ser or Thr) or 203 (Lys→Thr or Asn). A single amino acid substitution at residue 241 (Pro→Ser) was observed in 8E6-induced variants. Three-dimensional analysis showed that the epitopes for both MAbs were situated in close proximity to each other. Since B/Yamagata group strains are characterized by amino acid deletions at residues 164–166, the epitope for MAb 10B8 is strictly specific for B/Victoria group strains.

scholarly journals Caspase-Dependent N-Terminal Cleavage of Influenza Virus Nucleocapsid Protein in Infected Cells

1999 ◽  
Vol 73 (12) ◽  
pp. 10158-10163 ◽  
Author(s):  
O. P. Zhirnov ◽  
T. E. Konakova ◽  
W. Garten ◽  
H.-D. Klenk
Keyword(s):  
Nucleocapsid Protein ◽  
Influenza A ◽  
Influenza Viruses ◽  
Influenza B Virus ◽  
Influenza B ◽  
Cleavage Sites ◽  
Human Influenza ◽  
Influenza A Viruses ◽  
N Terminus ◽  
Infected Cells

ABSTRACT The nucleocapsid protein (NP) (56 kDa) of human influenza A viruses is cleaved in infected cells into a 53-kDa form. Likewise, influenza B virus NP (64 kDa) is cleaved into a 55-kDa protein with a 62-kDa intermediate (O. P. Zhirnov and A. G. Bukrinskaya, Virology 109:174–179, 1981). We show now that an antibody specific for the N terminus of influenza A virus NP reacted with the uncleaved 56-kDa form but not with the truncated NP53 form, indicating the removal of a 3-kDa peptide from the N terminus. Amino acid sequencing revealed the cleavage sites ETD16*G for A/Aichi/68 NP and sites DID7*G and EAD61*V for B/Hong Kong/72 NP. With D at position −1, acidic amino acids at position −3, and aliphatic ones at positions −2 and +1, the NP cleavage sites show a recognition motif typical for caspases, key enzymes of apoptosis. These caspase cleavage sites demonstrated evolutionary stability and were retained in NPs of all human influenza A and B viruses. NP of avian influenza viruses, which is not cleaved in infected cells, contains G instead of D at position 16. Oligopeptide DEVD derivatives, specific caspase inhibitors, were shown to prevent the intracellular cleavage of NP. All three events, the NP cleavage, the increase of caspase activity, and the development of apoptosis, coincide in cells infected with human influenza A and B viruses. The data suggest that intracellular cleavage of NP is exerted by host caspases and is associated with the development of apoptosis at the late stages of infection.

scholarly journals A Reverse Genetics Approach for Recovery of Recombinant Influenza B Viruses Entirely from cDNA

2002 ◽  
Vol 76 (22) ◽  
pp. 11744-11747 ◽  
Author(s):  
David Jackson ◽  
Andrew Cadman ◽  
Thomas Zurcher ◽  
Wendy S. Barclay
Keyword(s):  
Amino Acid ◽  
Influenza A ◽  
Amino Acid Change ◽  
Reverse Genetics ◽  
Single Gene ◽  
Neuraminidase Inhibitor ◽  
Influenza B Virus ◽  
Influenza B ◽  
B Virus

ABSTRACT The recovery of recombinant influenza A virus entirely from cDNA was recently described (9, 19). We adapted the technique for engineering influenza B virus and generated a mutant bearing an amino acid change E116G in the viral neuraminidase which was resistant in vitro to the neuraminidase inhibitor zanamivir. The method also facilitates rapid isolation of single-gene reassortants suitable as vaccine seeds and will aid further investigations of unique features of influenza B virus.

scholarly journals Immune Pressure on Polymorphous Influenza B Populations Results in Diverse Hemagglutinin Escape Mutants and Lineage Switching

Vaccines ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 125 ◽  
Author(s):  
Ewan P. Plant ◽  
Hasmik Manukyan ◽  
Jose L. Sanchez ◽  
Majid Laassri ◽  
Zhiping Ye
Keyword(s):  
Amino Acid ◽  
Human Population ◽  
Amino Acid Position ◽  
Progeny Virus ◽  
Influenza B Virus ◽  
Influenza B ◽  
Dependent Manner ◽  
Amino Acid Residues ◽  
Immune Pressure ◽  
Ha Protein

Mutations arise in the genomes of progeny viruses during infection. Mutations that occur in epitopes targeted by host antibodies allow the progeny virus to escape the host adaptive, B-cell mediated antibody immune response. Major epitopes have been identified in influenza B virus (IBV) hemagglutinin (HA) protein. However, IBV strains maintain a seasonal presence in the human population and changes in IBV genomes in response to immune pressure are not well characterized. There are two lineages of IBV that have circulated in the human population since the 1980s, B-Victoria and B-Yamagata. It is hypothesized that early exposure to one influenza subtype leads to immunodominance. Subsequent seasonal vaccination or exposure to new subtypes may modify subsequent immune responses, which, in turn, results in selection of escape mutations in the viral genome. Here we show that while some mutations do occur in known epitopes suggesting antibody escape, many mutations occur in other parts of the HA protein. Analysis of mutations outside of the known epitopes revealed that these mutations occurred at the same amino acid position in viruses from each of the two IBV lineages. Interestingly, where the amino acid sequence differed between viruses from each lineage, reciprocal amino acid changes were observed. That is, the virus from the Yamagata lineage become more like the Victoria lineage virus and vice versa. Our results suggest that some IBV HA sequences are constrained to specific amino acid codons when viruses are cultured in the presence of antibodies. Some changes to the known antigenic regions may also be restricted in a lineage-dependent manner. Questions remain regarding the mechanisms underlying these results. The presence of amino acid residues that are constrained within the HA may provide a new target for universal vaccines for IBV.

scholarly journals Comparison of the Mutation Rates of Human Influenza A and B Viruses

2006 ◽  
Vol 80 (7) ◽  
pp. 3675-3678 ◽  
Author(s):  
Eri Nobusawa ◽  
Katsuhiko Sato
Keyword(s):  
Genetic Diversity ◽  
Mutation Rate ◽  
Influenza A ◽  
Mdck Cells ◽  
Evolutionary Rates ◽  
Mutation Rates ◽  
Influenza B ◽  
Human Influenza ◽  
Influenza A Viruses ◽  
Infectious Cycle

ABSTRACT Human influenza A viruses evolve more rapidly than influenza B viruses. To clarify the cause of this difference, we have evaluated the mutation rate of the nonstructural gene as revealed by the genetic diversity observed during the growth of individual plaques in MDCK cells. Six plaques were studied, representing two strains each of type A and B viruses. A total of 813,663 nucleotides were sequenced, giving rates of 2.0 × 10−6 and 0.6 × 10−6 mutations per site per infectious cycle, which, when extended to 1 year, agree well with the published annual evolutionary rates.

scholarly journals The CPSF30 Binding Site on the NS1A Protein of Influenza A Virus Is a Potential Antiviral Target

2006 ◽  
Vol 80 (8) ◽  
pp. 3957-3965 ◽  
Author(s):  
Karen Y. Twu ◽  
Diana L. Noah ◽  
Ping Rao ◽  
Rei-Lin Kuo ◽  
Robert M. Krug
Keyword(s):  
Amino Acid ◽  
Binding Site ◽  
Influenza A Virus ◽  
Virus Replication ◽  
Influenza A ◽  
Influenza B Virus ◽  
Influenza B ◽  
Influenza A Viruses ◽  
B Virus ◽  
Ns1a Protein

ABSTRACT The emergence of influenza A viruses resistant to the two existing classes of antiviral drugs highlights the need for additional antiviral drugs, particularly considering the potential threat of a pandemic of H5N1 influenza A viruses. Here, we determine whether influenza A virus replication can be selectively inhibited by blocking the ability of its NS1A protein to inhibit the 3′-end processing of cellular pre-mRNAs, including beta interferon (IFN-β) pre-mRNA. Pre-mRNA processing is inhibited via the binding of the NS1A protein to the cellular CPSF30 protein, and mutational inactivation of this NS1A binding site causes severe attenuation of the virus. We demonstrate that binding of CPSF30 is mediated by two of its zinc fingers, F2F3, and that the CPSF30/F2F3 binding site on the NS1A protein extends from amino acid 144 to amino acid 186. We generated MDCK cells that constitutively express epitope-tagged F2F3 in the nucleus, although at only approximately one-eighth the level of the NS1A protein produced during virus infection. Influenza A virus replication was inhibited in this cell line, whereas no inhibition was observed with influenza B virus, whose NS1B protein lacks a binding site for CPSF30. Influenza A virus, but not influenza B virus, induced increased production of IFN-β mRNA in the F2F3-expressing cells. These results, which indicate that F2F3 inhibits influenza A virus replication by blocking the binding of endogenous CPSF30 to the NS1A protein, point to this NS1A binding site as a potential target for the development of antivirals directed against influenza A virus.

scholarly journals The contrasting phylodynamics of human influenza B viruses

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Dhanasekaran Vijaykrishna ◽  
Edward C Holmes ◽  
Udayan Joseph ◽  
Mathieu Fourment ◽  
Yvonne CF Su ◽  
...  
Keyword(s):  
Influenza A ◽  
Virus Transmission ◽  
Ecological Factors ◽  
Influenza Viruses ◽  
Influenza B Virus ◽  
Influenza B ◽  
Human Influenza ◽  
Influenza A Viruses ◽  
Binding Preference ◽  
Spatio Temporal

A complex interplay of viral, host, and ecological factors shapes the spatio-temporal incidence and evolution of human influenza viruses. Although considerable attention has been paid to influenza A viruses, a lack of equivalent data means that an integrated evolutionary and epidemiological framework has until now not been available for influenza B viruses, despite their significant disease burden. Through the analysis of over 900 full genomes from an epidemiological collection of more than 26,000 strains from Australia and New Zealand, we reveal fundamental differences in the phylodynamics of the two co-circulating lineages of influenza B virus (Victoria and Yamagata), showing that their individual dynamics are determined by a complex relationship between virus transmission, age of infection, and receptor binding preference. In sum, this work identifies new factors that are important determinants of influenza B evolution and epidemiology.

Global Epidemic Trend Analysis of Influenza Type B Drug Resistance Sites From 2006 To 2018

2021 ◽  
Author(s):  
He Li ◽  
Wei Dong ◽  
Die Yu ◽  
Dan Qian ◽  
Lihuan Yue ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Influenza Virus ◽  
Amino Acid ◽  
Phylogenetic Trees ◽  
Amino Acid Sequences ◽  
Influenza B Virus ◽  
Influenza B ◽  
Resistance Mutations ◽  
Sequence Alignments ◽  
B Virus

Abstract Background: Influenza is a severe respiratory viral infection that causes significant morbidity and mortality, due to annual epidemics and unpredictable pandemics. At present, drugs used in influenza virus B infection treatment are mainly neuraminidase inhibitors (NAIs). With the extensive use of NAI drugs, the influenza virus B has carried different drug-resistant mutations. This study aims to analyze the drug resistance mutations of the NA sequence in Flu B and provide guidance for clinical medication.Methods: Near full-length sequences of the NA region of all influenza B viruses from January 1, 2006 to December 31, 2018 were downloaded from public databases GISAID and NCBI. Multiple sequence alignments were performed using Clustal Omega 1.2.4 software. Subsequently, phylogenetic trees were constructed by FastTree 2.1.11 and clustered by ClusterPickergui_1.2.3.JAR. Then, the major drug resistance sites and surrounding auxiliary sites were analyzed by Mega-X and Weblogo (http://weblogo.threeplusone.com/) tools.Results: Among the amino acid sequences of neuraminidase (NA) from 2006 to 2018, only Cluster 4 in 2018 carried D197N mutation of NA active site, while other drug resistance sites were conserved without mutation. According to the Weblogo analysis, a large number of N198, S295, K373, and K375 mutations were found in the amino acid residues at the auxiliary sites surround D197, N294, and R374 in the influenza B virus.Conclusion: We found the D197N mutation in Cluster 4 of the 2018 influenza B virus, with a large number of N198, S295, K373, and K375 mutations in the helper sites around N197, N294, R374 from 2006 to 2018. NA inhibitors are currently the only kind of specific antiviral agent for the influenza B virus, although these mutations cause mild NAIs resistance.

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