scholarly journals Comparative Co-Evolution Analysis Between the HA and NA Genes of Influenza A Virus

2018 ◽  
Vol 9 ◽  
pp. 1178122X1878832 ◽  
Author(s):  
Jinhwa Jang ◽  
Se-Eun Bae
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Phylogenetic Trees ◽  
Strong Positive Correlation ◽  
Progeny Production ◽  
Ha Gene ◽  
Evolution Analysis ◽  
Event Based ◽  
Further Development ◽  
Na Gene

Influenza A virus subtypes are determined based on envelope proteins encoded by the hemagglutinin (HA) gene and the neuraminidase (NA) gene, which are involved in attachment to the host, pathogenicity, and progeny production. Here, we evaluated such differences through co-evolution analysis between the HA and NA genes based on subtype and host. Event-based cophylogeny analysis revealed that humans had higher cospeciation values than avian. In particular, the yearly ML phylogenetic trees for the H1N1 and H3N2 subtypes in humans displayed similar topologies between the two genes in humans. Substitution analysis was verifying the strong positive correlation between the two genes in the H1N1 and H3N2 subtypes in humans compared with those in avian and swine. These results provided a proof of principle for the further development of vaccines according to hosts and subtypes against Influenza A virus.

scholarly journals Rewiring the RNAs of influenza virus to prevent reassortment

2009 ◽  
Vol 106 (37) ◽  
pp. 15891-15896 ◽  
Author(s):  
Qinshan Gao ◽  
Peter Palese
Keyword(s):  
Influenza Virus ◽  
Influenza A Virus ◽  
Influenza A ◽  
Nonstructural Protein ◽  
Influenza Viruses ◽  
Ha Gene ◽  
Ns Gene ◽  
Virus Rna ◽  
Reassortant Viruses ◽  
Packaging Signals

Influenza viruses contain segmented, negative-strand RNA genomes. Genome segmentation facilitates reassortment between different influenza virus strains infecting the same cell. This phenomenon results in the rapid exchange of RNA segments. In this study, we have developed a method to prevent the free reassortment of influenza A virus RNAs by rewiring their packaging signals. Specific packaging signals for individual influenza virus RNA segments are located in the 5′ and 3′ noncoding regions as well as in the terminal regions of the ORF of an RNA segment. By putting the nonstructural protein (NS)-specific packaging sequences onto the ORF of the hemagglutinin (HA) gene and mutating the packaging regions in the ORF of the HA, we created a chimeric HA segment with the packaging identity of an NS gene. By the same strategy, we made an NS gene with the packaging identity of an HA segment. This rewired virus had the packaging signals for all eight influenza virus RNAs, but it lost the ability to independently reassort its HA or NS gene. A similar approach can be applied to the other influenza A virus segments to diminish their ability to form reassortant viruses.

scholarly journals Cooperation between the Hemagglutinin of Avian Viruses and the Matrix Protein of Human Influenza A Viruses

2002 ◽  
Vol 76 (4) ◽  
pp. 1781-1786 ◽  
Author(s):  
Christoph Scholtissek ◽  
Jürgen Stech ◽  
Scott Krauss ◽  
Robert G. Webster
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Matrix Protein ◽  
Gene Products ◽  
Human Influenza ◽  
Influenza A Viruses ◽  
M Gene ◽  
Human Virus ◽  
Ha Gene ◽  
M Proteins

ABSTRACT To analyze the compatibility of avian influenza A virus hemagglutinins (HAs) and human influenza A virus matrix (M) proteins M1 and M2, we doubly infected Madin-Darby canine kidney cells with amantadine (1-aminoadamantane hydrochloride)-resistant human viruses and amantadine-sensitive avian strains. By using antisera against the human virus HAs and amantadine, we selected reassortants containing the human virus M gene and the avian virus HA gene. In our system, high virus yields and large, well-defined plaques indicated that the avian HAs and the human M gene products could cooperate effectively; low virus yields and small, turbid plaques indicated that cooperation was poor. The M gene products are among the primary components that determine the species specificities of influenza A viruses. Therefore, our system also indicated whether the avian HA genes effectively reassorted into the genome and replaced the HA gene of the prevailing human influenza A viruses. Most of the avian HAs that we tested efficiently cooperated with the M gene products of the early human A/PR/8/34 (H1N1) virus; however, the avian HAs did not effectively cooperate with the most recently isolated human virus that we tested, A/Nanchang/933/95 (H3N2). Cooperation between the avian HAs and the M proteins of the human A/Singapore/57 (H2N2) virus was moderate. These results suggest that the currently prevailing human influenza A viruses might have lost their ability to undergo antigenic shift and therefore are unable to form new pandemic viruses that contain an avian HA, a finding that is of great interest for pandemic planning.

scholarly journals Reassortment Network of Influenza A Virus

2021 ◽  
Vol 12 ◽  
Author(s):  
Xingfei Gong ◽  
Mingda Hu ◽  
Wei Chen ◽  
Haoyi Yang ◽  
Boqian Wang ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Phylogenetic Trees ◽  
Minimum Spanning Tree ◽  
Comprehensive Understanding ◽  
Genome Sequences ◽  
Genetic Characteristics ◽  
Time Period ◽  
Genome Wide ◽  
History Of

Influenza A virus (IAV) genomes are composed of eight single-stranded RNA segments. Genetic exchange through reassortment of the segmented genomes often endows IAVs with new genetic characteristics, which may affect transmissibility and pathogenicity of the viruses. However, a comprehensive understanding of the reassortment history of IAVs remains lacking. To this end, we assembled 40,296 whole-genome sequences of IAVs for analysis. Using a new clustering method based on Mean Pairwise Distances in the phylogenetic trees, we classified each segment of IAVs into clades. Correspondingly, reassortment events among IAVs were detected by checking the segment clade compositions of related genomes under specific environment factors and time period. We systematically identified 1,927 possible reassortment events of IAVs and constructed their reassortment network. Interestingly, minimum spanning tree of the reassortment network reproved that swine act as an intermediate host in the reassortment history of IAVs between avian species and humans. Moreover, reassortment patterns among related subtypes constructed in this study are consistent with previous studies. Taken together, our genome-wide reassortment analysis of all the IAVs offers an overview of the leaping evolution of the virus and a comprehensive network representing the relationships of IAVs.

scholarly journals Natural Selection Determines Synonymous Codon Usage Patterns of Neuraminidase (NA) Gene of the Different Subtypes of Influenza A Virus in Canada

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Youhua Chen
Keyword(s):  
Natural Selection ◽  
Codon Usage ◽  
Influenza A Virus ◽  
Influenza A ◽  
Synonymous Codon ◽  
Phylogenetic Signal ◽  
Synonymous Codon Usage ◽  
Usage Patterns ◽  
Na Sequences ◽  
Na Gene

Synonymous codon usage patterns of neuraminidase (NA) gene of 64 subtypes (one is a mixed subtype) of influenza A virus found in Canada were analyzed. In total, 1422 NA sequences were analyzed. Among the subtypes, H1N1 is the prevailing one with 516 NCBI accession records, followed by H3N2, H3N8, and H4N6. The year of 2009 has the highest report records for the NA sequences in Canada, corresponding to the 2009 pandemic event. Correspondence analysis on the RSCU values of the four major subtypes showed that they had distinct clustering patterns in the two-dimensional scatter plot, indicating that different subtypes of IAV utilized different preferential codons. This subtype clustering pattern implied the important influence of natural selection, which could be further evidenced by an extremely flattened regression line in the neutrality plot (GC12 versus G3s plot) and a significant phylogenetic signal on the distribution of different subtypes in the clades of the phylogenetic tree (λ statistic). In conclusion, different subtypes of IAV showed an evolutionary differentiation on choosing different optimal codons. Natural selection played a deterministic role to structure IAV codon usage patterns in Canada.

scholarly journals A release-competent influenza A virus mutant lacking the coding capacity for the neuraminidase active site

2002 ◽  
Vol 83 (11) ◽  
pp. 2683-2692 ◽  
Author(s):  
Larisa V. Gubareva ◽  
Marina S. Nedyalkova ◽  
Dmitri V. Novikov ◽  
K. Gopal Murti ◽  
Erich Hoffmann ◽  
...  
Keyword(s):  
Cell Culture ◽  
Influenza A Virus ◽  
Active Site ◽  
Influenza A ◽  
Mdck Cells ◽  
Compensatory Mechanism ◽  
Receptor Binding Site ◽  
Virus Surface ◽  
Ha Gene ◽  
Coding Capacity

Both influenza A virus surface glycoproteins, the haemagglutinin (HA) and neuraminidase (NA), interact with neuraminic acid-containing receptors. The influenza virus A/Charlottesville/31/95 (H1N1) has shown a substantially reduced sensitivity to NA inhibitor compared with the A/WSN/33 (H1N1) isolate by plaque-reduction assays in Madin–Darby canine kidney (MDCK) cells. However, there was no difference in drug sensitivity in an NA inhibition assay. The replacement of the HA gene of A/WSN/33 with the HA gene of A/Charlottesville/31/95 led to a drastic reduction in sensitivity of A/WSN/33 to NA inhibitor in MDCK cells. Passage of A/Charlottesville/31/95 in cell culture in the presence of an NA inhibitor resulted in the emergence of mutant viruses (delNA) whose genomes lacked the coding capacity for the NA active site. The delNA mutants were plaque-to-plaque purified and further characterized. The delNA-31 mutant produced appreciable yields (∼106 p.f.u./ml) in MDCK cell culture supernatants in the absence of viral or bacterial NA activity. Sequence analysis of the delNA mutant genome revealed no compensatory substitutions in the HA or other genes compared with the wild-type. Our data indicate that sialylation of the oligosaccharide chains in the vicinity of the HA receptor-binding site of A/Charlottesville/31/95 virus reduces the HA binding efficiency and thus serves as a compensatory mechanism for the loss of NA activity. Hyperglycosylation of HA is common in influenza A viruses circulating in humans and has the potential to reduce virus sensitivity to NA inhibitors.

scholarly journals DESIGNING AND CLONING NA GENE OF INFLUENZA A/H5N1 VIRUS INTO pHW2000 VECTOR FOR PREPARATION OF A CANDIDATE VACCINE MASTERSEED STRAIN

2018 ◽  
Vol 16 (2) ◽  
pp. 369-376
Author(s):  
Nguyen Thi Thu Hang ◽  
Hoang Thi Thu Hang ◽  
Nguyen Hung Chi ◽  
Vu Huyen Trang ◽  
Chu Hoang Ha ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Influenza A Virus ◽  
Influenza A ◽  
H5n1 Virus ◽  
Reverse Genetics ◽  
Influenza A Viruses ◽  
Highly Pathogenic ◽  
Clade 2.3.2.1C ◽  
Na Gene ◽  
Recombinant Vectors

The influenza A/H5N1 virus is an RNA virus belonging to the family of Orthomyxoviridae. The highly pathogenic influenza A/H5N1 virus exhibit the ability to cause high mortality in poultry and infect humans. Technology for vaccine seed strain production of influenza A virus using reverse genetics requires the creation of recombinant vectors carrying viral genomic segments. To create recombinant pHW2000 vectors containing the neuraminidase (NA) gene segment encoding an important surface antigen of influenza A virus, two N1 NA gene structures were designed based on the NA gene sequences of two subtypes of highly pathogenic influenza A/H5N1 clade (clade 1.1 and clade 2.3.2.1c) and then inserted into pHW2000 vector. These two clades of highly pathogenic avian influenza viruses that are still circulating in Vietnam, with antigen homology and genetic relationships to many strains of influenza A viruses, have been suggested to be used for producing vaccines against emerging avian influenza A/H5N1 virus. Each NA gene construct consists of 1453 nucleotides in which two ends of the gene are two non-coding regions (46 nucleotides and 57 nucleotides) containing primer binding site and cleavage site of BsaI. In the middle of each NA gene is one region of 1350 nucleotides encoding 449 amino acids, ensuring catalytic function and antigenicity of NA protein. Two NA segments corresponding to the two clades of influenza A viruses were successfully cloned into pHW2000 vectors for the generation of two recombinant vectors pHW2000-NA clade 1.1 and pHW2000-NA clade 2.3.2.1c. These recombinant vectors will be used for production of candidate avian influenza vaccine strains using reverse genetics technique.

Comparative studies on variability, phylogenesis, and correlated mutations of neuraminidases from influenza virus type A

2018 ◽  
Vol 14 (1) ◽  
Author(s):  
Rafał Filip ◽  
Jacek Leluk
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Phylogenetic Trees ◽  
Evolutionary Relationship ◽  
Specific Inhibitor ◽  
Influenza A Viruses ◽  
New Information ◽  
Sialic Acid Receptors ◽  
Bioinformatics Software ◽  
Correlated Mutations

Abstract Neuraminidase (NA) is an important protein for the replication cycle of influenza A viruses. NA is an enzyme that cleaves the sialic acid receptors; this process plays a significant role in viral life cycle. Blocking NA with a specific inhibitor is an effective way to treat the flu. However, some strains show resistance to current drugs. Therefore, NA is the focus for the intense research for new antiviral drugs and also for the explanation of the functions of new mutations. This research focuses on determining the profile of variability and phylogenetic analysis and finding the correlated mutations within a set of 149 sequences of NA belonging to various strains of influenza A virus. In this study, we have used the original programs (Corm, Consensus Constructor, and SSSSg) and also other bioinformatics software. NA proteins are characterized by various levels of variability in different regions, which was presented in detail with the aid of ConSurf. The use of four independent methods to create the phylogenetic trees gave some new data on the evolutionary relationship within the NA family proteins. The search for correlated mutations shows several potentially important correlated positions that were not reported previously to be significant. The use of such an approach can be potentially important and gives new information regarding NA proteins of influenza A virus.

Molecular Characterization of Influenza A Viruses Detected in Children Attending Yangon Children’s Hospital, 2016

2019 ◽  
Vol 31 (1) ◽  
pp. 72-80
Keyword(s):  
Phylogenetic Analysis ◽  
Influenza A Virus ◽  
Influenza A ◽  
Epidemiological Studies ◽  
Influenza Viruses ◽  
Influenza B Virus ◽  
Influenza B ◽  
Influenza A Viruses ◽  
B Virus ◽  
Na Gene

Sequence analysis of the influenza virus strains is important for molecular epidemiological studies and evolutional studies of influenza viruses as well as for the assessment of vaccine effectiveness. The aim of this study was to determine and characterize predominant subtype of influenza A viruses among children attending Yangon Children’s Hospital (YCH). It was a cross-sectional descriptive study conducted at YCH. Nasopharyngeal swabs were collected from 153 children who attended the hospital due to influenza-like illness (ILI) during January-December, 2016. Viral RNA was extracted by QIAamp® Viral Mini Kit. Matrix genes of influenza A and influenza B virus were detected by multiplex Reverse TranscriptionPolymerase Chain Reaction (RT-PCR). Influenza A virus matrix gene positive samples were subjected to subtyping. Predominant subtypes were subjected to sequencing and phylogenetic analysis of their HA gene and neuraminidase (NA) gene. Influenza viruses were detected in about 14% of children with ILI. Among them, 55% showed influenza A virus positive and 45% showed influenza B virus positive. Influenza A (H3N2) virus was found to be predominant among influenza A virus positive children accounting for 83.4%. There was one case (8.3%) of influenza A (H1N1) pdm09 virus and one case (8.3%) of unsubtyped influenza A virus. Phylogenetic analysis of HA and NA gene of two Myanmar strains of H3N2 subtype revealed that they belonged to clade 3C.2a1. They had 99.3-99.4% nucleotide identity with A/Hong Kong/ 4801/2014, vaccine strain of H3N2 subtype, that was contained in southern hemisphere influenza vaccine for 2016 and northern hemisphere vaccine for 2016-2017 season. This study generated information useful for the assessment of influenza outbreaks, selection of upcoming vaccine strains and further evolutionary and epidemiological studies on influenza viruses.

The strong positive correlation between effective affinity and infectivity neutralization of highly cross-reactive monoclonal antibody IIB4, which recognizes antigenic site B on influenza A virus haemagglutinin

Microbiology ◽  
2000 ◽  
Vol 81 (7) ◽  
pp. 1727-1735 ◽  
Author(s):  
F. Kostolanský ◽  
E. Varečková ◽  
T. Betáková ◽  
V. Mucha ◽  
G. Russ ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Influenza A Virus ◽  
Influenza A ◽  
Antigenic Site ◽  
Fold Increase ◽  
Cross Reactivity ◽  
Influenza Viruses ◽  
Mass Action ◽  
Strong Positive Correlation ◽  
Positive Correlation

Monoclonal antibody (MAb) IIB4 displays a rare combination of virus neutralization (VN) activity and broad cross-reactivity with influenza A virus strains of the H3 subtype isolated in a period from 1973 to 1988. The epitope of this antibody has been identified as around HA1 residues 198, 199 and 201. Here we report that residues 155, 159, 188, 189 and 193 also influence the binding of this antibody. We have used this antibody to study the relationship between antibody affinity and VN activity. Using one MAb and a single epitope on the haemagglutinin (HA) of different influenza viruses we found a strong positive correlation between effective affinity and VN activity of MAb IIB4. A 10-fold increase in effective affinity corresponded to the 2000-fold increase in VN titre. It follows from the law of mass action that for an effective affinity K=9×108 l/mol, 50% VN was achieved at approx. 10% occupation of HA spikes with antibody. In contrast, for an effective affinity K=6×107 l/mol, to achieve 50% VN, occupation of up to 98% of HA spikes was required. An effective affinity about K=6×107 l/mol thus represents the limiting value for VN because a further decrease in the affinity cannot be compensated by a higher concentration of antibody.

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