scholarly journals Common Features of Coronavirus and Influenza Pandemics and Surface Proteins of their Pathogens. Parallels

2021 ◽  
Vol 20 (4) ◽  
pp. 4-18
Author(s):  
E. P. Kharchenko
Keyword(s):  
Amino Acids ◽  
Influenza Virus ◽  
Influenza Viruses ◽  
Surface Proteins ◽  
S Protein ◽  
Common Features ◽  
Influenza Pandemics ◽  
Intrinsically Disordered Regions ◽  
Pandemic Virus ◽  
Virus Strains

Relevance. Coronaviruses and influenza viruses induce pandemics taking away many human lives and seeding social-economic chaos. Possibility to prognose pandemic features on characteristics of surface proteins of their pathogens is not investigated.Aim is to characterize the common features of the pandemic coronavirus S-protein and the pandemic virus influenza hemagglutinin in connection with the features of a coronavirus pandemic and influenza pandemics.Materials and method. For the bioinformatic analysis the protein sequences of pandemic coronavirus strains and pandemic influenza virus strains, influenza virus strains of 2017–2018 season and also influenza virus type B strains were used. In proteins an amino acid content, the sums of the charged amino acids and the.Results. It was found out that the increase of amount of the amino acids forming intrinsically disordered regions in the coronavirus S-protein S1 subunit and influenza virus H1 hemagglutinin HA1 subunit is characteristic of the pandemics with high morbidity and the increase of arginine and lysine with comparison with aspartic and glutamic acids in those proteins is peculiar to viruses inducing the pandemics with lower lethality.Conclusion. The features (morbidity and lethality) of the coronavirus pandemic and influenza virus pandemic are associated with the quantitative amino acids content of pandemic virus surface proteins.

A Study on Host Tropism Determinants of Influenza Virus Using Machine Learning

2020 ◽  
Vol 15 (2) ◽  
pp. 121-134 ◽  
Author(s):  
Eunmi Kwon ◽  
Myeongji Cho ◽  
Hayeon Kim ◽  
Hyeon S. Son
Keyword(s):  
Machine Learning ◽  
Amino Acids ◽  
Influenza Virus ◽  
Random Forest ◽  
Physicochemical Properties ◽  
Protein Sequences ◽  
Influenza Viruses ◽  
Host Tropism ◽  
Post Hoc ◽  
Ha Protein

Background: The host tropism determinants of influenza virus, which cause changes in the host range and increase the likelihood of interaction with specific hosts, are critical for understanding the infection and propagation of the virus in diverse host species. Methods: Six types of protein sequences of influenza viral strains isolated from three classes of hosts (avian, human, and swine) were obtained. Random forest, naïve Bayes classification, and knearest neighbor algorithms were used for host classification. The Java language was used for sequence analysis programming and identifying host-specific position markers. Results: A machine learning technique was explored to derive the physicochemical properties of amino acids used in host classification and prediction. HA protein was found to play the most important role in determining host tropism of the influenza virus, and the random forest method yielded the highest accuracy in host prediction. Conserved amino acids that exhibited host-specific differences were also selected and verified, and they were found to be useful position markers for host classification. Finally, ANOVA analysis and post-hoc testing revealed that the physicochemical properties of amino acids, comprising protein sequences combined with position markers, differed significantly among hosts. Conclusion: The host tropism determinants and position markers described in this study can be used in related research to classify, identify, and predict the hosts of influenza viruses that are currently susceptible or likely to be infected in the future.

Inhibition of ciliary activity in organ cultures of ferret trachea in reference to genetic and biological characters of influenza virus strains

1982 ◽  
Vol 28 (7) ◽  
pp. 809-814 ◽  
Author(s):  
P. Diaz-Rodriguez ◽  
A. Boudreault
Keyword(s):  
Influenza Virus ◽  
Influenza Viruses ◽  
Influenza Vaccines ◽  
Ciliary Activity ◽  
Organ Cultures ◽  
Preliminary Screening ◽  
Cold Adapted ◽  
Activity Inhibition ◽  
Biological Characters ◽  
Virus Strains

As reported previously, attenuated stable inhibitor-resistant influenza viruses can be screened by a 50% ciliary activity inhibition test in ferret tracheal organ cultures. This test was further applied to 5 attenuated cold-adapted influenza strains and to 11 strains with known a percentage of RNA–RNA hybridization with the parental A/PR/8/34 (H0N1) virus strain. Again, with one exception, attenuated strains could be clearly differentiated from virulent ones. It was concluded that virulence of influenza strains for man can be detected using this test regardless of the techniques used to prepare attenuated variants. A preliminary screening of attenuated candidates for live influenza vaccines can be achieved with confidence on ferret tracheal organ cultures.

scholarly journals Functional Analysis of PA Binding by Influenza A Virus PB1: Effects on Polymerase Activity and Viral Infectivity

2001 ◽  
Vol 75 (17) ◽  
pp. 8127-8136 ◽  
Author(s):  
Daniel R. Perez ◽  
Ruben O. Donis
Keyword(s):  
Amino Acids ◽  
Influenza Virus ◽  
Amino Acid ◽  
Viral Replication ◽  
Influenza A Virus ◽  
Influenza A ◽  
Amino Acid Sequences ◽  
Influenza Viruses ◽  
Virus Growth ◽  
Transcription And Replication

ABSTRACT Influenza A virus expresses three viral polymerase (P) subunits—PB1, PB2, and PA—all of which are essential for RNA and viral replication. The functions of P proteins in transcription and replication have been partially elucidated, yet some of these functions seem to be dependent on the formation of a heterotrimer for optimal viral RNA transcription and replication. Although it is conceivable that heterotrimer subunit interactions may allow a more efficient catalysis, direct evidence of their essentiality for viral replication is lacking. Biochemical studies addressing the molecular anatomy of the P complexes have revealed direct interactions between PB1 and PB2 as well as between PB1 and PA. Previous studies have shown that the N-terminal 48 amino acids of PB1, termed domain α, contain the residues required for binding PA. We report here the refined mapping of the amino acid sequences within this small region of PB1 that are indispensable for binding PA by deletion mutagenesis of PB1 in a two-hybrid assay. Subsequently, we used site-directed mutagenesis to identify the critical amino acid residues of PB1 for interaction with PA in vivo. The first 12 amino acids of PB1 were found to constitute the core of the interaction interface, thus narrowing the previous boundaries of domain α. The role of the minimal PB1 domain α in influenza virus gene expression and genome replication was subsequently analyzed by evaluating the activity of a set of PB1 mutants in a model reporter minigenome system. A strong correlation was observed between a functional PA binding site on PB1 and P activity. Influenza viruses bearing mutant PB1 genes were recovered using a plasmid-based influenza virus reverse genetics system. Interestingly, mutations that rendered PB1 unable to bind PA were either nonviable or severely growth impaired. These data are consistent with an essential role for the N terminus of PB1 in binding PA, P activity, and virus growth.

scholarly journals Influenza Virus Resistance to Human Neutralizing Antibodies

mBio ◽  
2012 ◽  
Vol 3 (4) ◽  
Author(s):  
James E. Crowe
Keyword(s):  
Influenza Virus ◽  
B Cell ◽  
Neutralizing Antibodies ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Influenza Viruses ◽  
Surface Proteins ◽  
Progeny Virus ◽  
Human Antibody ◽  
Functional Surface

ABSTRACT The human antibody repertoire has an exceptionally large capacity to recognize new or changing antigens through combinatorial and junctional diversity established at the time of V(D)J recombination and through somatic hypermutation. Influenza viruses exhibit a relentless capacity to escape the human antibody response by altering the amino acids of their surface proteins in hypervariable domains that exhibit a high level of structural plasticity. Both parties in this high-stakes game of shape shifting drive structural evolution of their functional proteins (the B cell receptor/antibody on one side and the viral hemagglutinin and neuraminidase proteins on the other) using error-prone polymerase systems. It is likely that most of the genetic mutations that occur in these systems are deleterious, resulting in the failure of the B cell or virus with mutations to propagate in the immune repertoire or viral quasispecies. A subset of mutations is tolerated in functional surface proteins that enter the B cell or virus progeny pool. In both cases, selection occurs in the population of mutated and unmutated species. In cases where the functional avidity of the B cell receptor is increased significantly, that clone may be selected for preferential expansion. In contrast, an influenza virus that “escapes” the inhibitory effect of secreted antibodies may represent a high proportion of the progeny virus in that host. The recent paper by O’Donnell et al. [C. D. O’Donnell et al., mBio 3(3):e00120-12, 2012] identifies a mechanism for antibody resistance that does not require escape from binding but rather achieves a greater efficiency in replication.

scholarly journals Immunomic Analysis of the Repertoire of T-Cell Specificities for Influenza A Virus in Humans

2008 ◽  
Vol 82 (24) ◽  
pp. 12241-12251 ◽  
Author(s):  
Erika Assarsson ◽  
Huynh-Hoa Bui ◽  
John Sidney ◽  
Qing Zhang ◽  
Jean Glenn ◽  
...  
Keyword(s):  
Influenza Virus ◽  
T Cell ◽  
Influenza A Virus ◽  
Influenza A ◽  
T Cell Responses ◽  
Class Ii ◽  
Influenza Viruses ◽  
Class I ◽  
Cell Responses ◽  
Virus Strains

ABSTRACT Continuing antigenic drift allows influenza viruses to escape antibody-mediated recognition, and as a consequence, the vaccine currently in use needs to be altered annually. Highly conserved epitopes recognized by effector T cells may represent an alternative approach for the generation of a more universal influenza virus vaccine. Relatively few highly conserved epitopes are currently known in humans, and relatively few epitopes have been identified from proteins other than hemagglutinin and nucleoprotein. This prompted us to perform a study aimed at identifying a set of human T-cell epitopes that would provide broad coverage against different virus strains and subtypes. To provide coverage across different ethnicities, seven different HLA supertypes were considered. More than 4,000 peptides were selected from a panel of 23 influenza A virus strains based on predicted high-affinity binding to HLA class I or class II and high conservancy levels. Peripheral blood mononuclear cells from 44 healthy human blood donors were tested for reactivity against HLA-matched peptides by using gamma interferon enzyme-linked immunospot assays. Interestingly, we found that PB1 was the major target for both CD4+ and CD8+ T-cell responses. The 54 nonredundant epitopes (38 class I and 16 class II) identified herein provided high coverage among different ethnicities, were conserved in the majority of the strains analyzed, and were consistently recognized in multiple individuals. These results enable further functional studies of T-cell responses during influenza virus infection and provide a potential base for the development of a universal influenza vaccine.

scholarly journals The analysis of the monoclonal immune response to influenza virus. II. The antigenicity of the viral hemagglutinin.

1976 ◽  
Vol 144 (4) ◽  
pp. 985-995 ◽  
Author(s):  
W Gerhard
Keyword(s):  
Immune Response ◽  
Influenza Virus ◽  
Monoclonal Antibodies ◽  
Influenza Viruses ◽  
Antigenic Determinants ◽  
Humoral Immune ◽  
Viral Hemagglutinin ◽  
Or Groups ◽  
Virus Strains

The antigenicity of the hemagglutinins (HA) of five influenza viruses of the A0 and A1 subtypes has been analyzed by means of monoclonal antibodies of murine origin produced in vitro. Secondary monoclonal anti-HA(PR8) antibodies were able to differentiate 14 antigenic determinants (or groups of determinants) on the HA of five influenza virus strains of the A0 and A1 subtypes. Taking into account that certain pairs of determinants delineated on heterologous HA may reflect the heterogeneity of the humoral immune response to a single homologous determinant, the presence of at least eight determinants (host cell-derived determinants not included) on the homologous HA of PR8 and probably on the HA of influenza viruses in general is postulated. Three types of HA-determinants of A0 and A1 influenza virus strains could be distinguished: strain-specific, partially shared, and determinant(s) common to all five virus strains tested. Roughly 40, 55, and 5%, respectively, of the secondary anti-PR8 antibodies of BALB/c mice were directed against determinants belonging to either of the three types.

scholarly journals Exploration of the 150 cavity and the role of serendipity in the discovery of inhibitors of influenza virus A neuraminidase

2018 ◽  
Vol 96 (2) ◽  
pp. 91-101 ◽  
Author(s):  
Sankar Mohan ◽  
B. Mario Pinto
Keyword(s):  
Influenza Virus ◽  
Influenza Viruses ◽  
Neuraminidase Inhibitors ◽  
Avian Influenza Viruses ◽  
Replication Process ◽  
Bird Population ◽  
Influenza Pandemics ◽  
New Class ◽  
Mutant Strains

Influenza pandemics are an ongoing threat for the human population, as the avian influenza viruses H5N1 and H7N9 continue to circulate in the bird population and the chance of avian to human transmission increases. Neuraminidase, a glycoprotein located on the surface of the influenza virus, plays a crucial role in the viral replication process and, hence, has proven to be a useful target enzyme for the treatment of influenza infections. The discovery that certain subtypes of influenza neuraminidase have an additional cavity, the 150 cavity, near the substrate binding site has triggered considerable interest in the design of influenza inhibitors that exploit this feature. Currently available antiviral drugs, neuraminidase inhibitors oseltamivir and zanamivir, were designed using crystal structures predating this discovery by some years. This mini review is aimed at summarizing our group’s efforts, together with related work from other groups, on neuraminidase inhibitors that are designed to exploit both the catalytic site and the 150 cavity. The design of a parent scaffold that yields a potent inhibitor that is active in cell culture assays and retains activity against several neuraminidases from mutant strains is also described. Finally, the role of serendipity in the discovery of a new class of potent neuraminidase inhibitors with a novel spirolactam scaffold is also highlighted.

The cap-binding site of influenza virus protein PB2 as a drug target

2016 ◽  
Vol 72 (2) ◽  
pp. 245-253 ◽  
Author(s):  
Chelsea Severin ◽  
Tales Rocha de Moura ◽  
Yong Liu ◽  
Keqin Li ◽  
Xiaofeng Zheng ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Binding Site ◽  
Structural Changes ◽  
Hydrophobic Interactions ◽  
Influenza Viruses ◽  
Virus Protein ◽  
Mrna Transcription ◽  
Viral Mrnas ◽  
Multiple Strains ◽  
Virus Strains

The RNA polymerase of influenza virus consists of three subunits: PA, PB1 and PB2. It uses a unique `cap-snatching' mechanism for the transcription of viral mRNAs. The cap-binding domain of the PB2 subunit (PB2cap) in the viral polymerase binds the cap of a host pre-mRNA molecule, while the endonuclease of the PA subunit cleaves the RNA 10–13 nucleotides downstream from the cap. The capped RNA fragment is then used as the primer for viral mRNA transcription. The structure of PB2cap from influenza virus H1N1 A/California/07/2009 and of its complex with the cap analog m7GTP were solved at high resolution. Structural changes are observed in the cap-binding site of this new pandemic influenza virus strain, especially the hydrophobic interactions between the ligand and the target protein. m7GTP binds deeper in the pocket than some other virus strains, much deeper than the host cap-binding proteins. Analysis of the new H1N1 structures and comparisons with other structures provide new insights into the design of small-molecule inhibitors that will be effective against multiple strains of both type A and type B influenza viruses.

scholarly journals Molecular Determinants within the Surface Proteins Involved in the Pathogenicity of H5N1 Influenza Viruses in Chickens

2004 ◽  
Vol 78 (18) ◽  
pp. 9954-9964 ◽  
Author(s):  
Diane J. Hulse ◽  
Robert G. Webster ◽  
Rupert J. Russell ◽  
Daniel R. Perez
Keyword(s):  
Amino Acids ◽  
Avian Influenza ◽  
Cleavage Site ◽  
Glycosylation Site ◽  
Influenza Viruses ◽  
Surface Proteins ◽  
Avian Influenza Viruses ◽  
Highly Pathogenic ◽  
H5n1 Influenza ◽  
High Pathogenicity

ABSTRACT Although it is established that the cleavage site and glycosylation patterns in the hemagglutinin (HA) play important roles in determining the pathogenicity of H5 avian influenza viruses, some viruses exist that are not highly pathogenic despite possessing the known characteristics of high pathogenicity (i.e., their HA contains multiple basic amino acids at the cleavage site and has glycosylation patterns similar to that of the highly pathogenic H5 viruses). Currently little is known about the H5N1 viruses that fall into this intermediate category of pathogenicity. We have identified strains of H5N1 avian influenza viruses that have markers typical of high pathogenicity but distinctly differ in their ability to cause disease and death in chickens. By analyzing viruses constructed by reverse-genetic methods and containing recombinant HAs, we established that amino acids 97, 108, 126, 138, 212, and 217 of HA, in addition to those within the cleavage site, affect pathogenicity. Further investigation revealed that an additional glycosylation site within the neuraminidase (NA) protein globular head contributed to the high virulence of the H5N1 virus. Our findings are in agreement with previous observations that suggest that the activities of the HA and NA proteins are functionally linked.

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