scholarly journals Molecular Dynamics Study of the Interaction Between RNA-Binding Domain of NS1 Influenza A Virus and Various Types of Carbon Nanotubes

2019 ◽  
Vol 116 (3) ◽  
pp. 398 ◽  
Author(s):  
Sara Az'hari Anon ◽  
Hamid Mosaddeghi ◽  
Yousef Ghayeb
Keyword(s):  
Carbon Nanotubes ◽  
Molecular Dynamics ◽  
Influenza A Virus ◽  
Influenza A ◽  
Rna Binding ◽  
Binding Domain ◽  
Rna Binding Domain

scholarly journals Structural Basis of the Influenza A Virus RNA Polymerase PB2 RNA-binding Domain Containing the Pathogenicity-determinant Lysine 627 Residue

2009 ◽  
Vol 284 (11) ◽  
pp. 6855-6860 ◽  
Author(s):  
Takashi Kuzuhara ◽  
Daisuke Kise ◽  
Hiroko Yoshida ◽  
Takahiro Horita ◽  
Yoshimi Murazaki ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Influenza A Virus ◽  
Influenza A ◽  
Rna Binding ◽  
Binding Domain ◽  
Structural Basis ◽  
Virus Rna ◽  
Pathogenicity Determinant ◽  
Rna Binding Domain

scholarly journals Molecular Dynamics Simulations of Influenza A Virus NS1 Reveal a Remarkably Stable RNA-Binding Domain Harboring Promising Druggable Pockets

Viruses ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 537
Author(s):  
Hiba Abi Hussein ◽  
Colette Geneix ◽  
Camille Cauvin ◽  
Daniel Marc ◽  
Delphine Flatters ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Influenza A ◽  
Rna Binding ◽  
Biological Activities ◽  
Binding Domain ◽  
Structural Protein ◽  
Binding Interface ◽  
Rna Binding Domain ◽  
Dynamics Simulations

The non-structural protein NS1 of influenza A viruses is considered to be the major antagonist of the interferon system and antiviral defenses of the cell. It could therefore represent a suitable target for novel antiviral strategies. As a first step towards the identification of small compounds targeting NS1, we here investigated the druggable potential of its RNA-binding domain since this domain is essential to the biological activities of NS1. We explored the flexibility of the full-length protein by running molecular dynamics simulations on one of its published crystal structures. While the RNA-binding domain structure was remarkably stable along the simulations, we identified a flexible site at the two extremities of the “groove” that is delimited by the antiparallel α-helices that make up its RNA-binding interface. This groove region is able to form potential binding pockets, which, in 60% of the conformations, meet the druggability criteria. We characterized these pockets and identified the residues that contribute to their druggability. All the residues involved in the druggable pockets are essential at the same time to the stability of the RNA-binding domain and to the biological activities of NS1. They are also strictly conserved across the large sequence diversity of NS1, emphasizing the robustness of this search towards the identification of broadly active NS1-targeting compounds.

scholarly journals The RNA Binding Domain of Influenza A Virus NS1 Protein Affects Secretion of Tumor Necrosis Factor Alpha, Interleukin-6, and Interferon in Primary Murine Tracheal Epithelial Cells

2007 ◽  
Vol 81 (17) ◽  
pp. 9469-9480 ◽  
Author(s):  
Celeste M. Newby ◽  
Leah Sabin ◽  
Andrew Pekosz
Keyword(s):  
Epithelial Cells ◽  
Influenza A Virus ◽  
Influenza A ◽  
Rna Binding ◽  
Binding Domain ◽  
Wild Type Virus ◽  
Ns1 Protein ◽  
Necrosis Factor Alpha ◽  
Tracheal Epithelial ◽  
Rna Binding Domain

ABSTRACT Primary differentiated respiratory epithelial cell cultures closely model the in vivo environment and allow for studies of innate immune responses generated specifically by epithelial cells, the primary cell type infected by human influenza A virus strains. We used primary murine tracheal epithelial cell (mTEC) cultures to investigate antiviral and cytokine responses to influenza A virus infection, focusing on the contribution of the RNA binding domain of the NS1 protein. rWSN NS1 R38A replication is attenuated in mTEC cultures; however, viral antigen is detected predominantly in ciliated cells, similar to wild-type virus. NS1 and NS1 R38A proteins display a primarily cytoplasmic localization in infected mTEC cultures. Increased production of tumor necrosis factor alpha, interleukin-6, and beta interferon is observed during rWSN NS1 R38A infection, and cytokines are secreted in a directional manner. Cytokine pretreatment of mTEC cultures and Vero cells suggest that rWSN NS1 R38A is more sensitive to the presence of antiviral/inflammatory cytokines than wild-type virus. Our results demonstrate that the RNA binding domain is a critical regulator of both cytokine production and cytokine sensitivity during influenza A virus infection of primary tracheal epithelial cells.

scholarly journals Molecular Dynamics Studies of the Nucleoprotein of Influenza A Virus: Role of the Protein Flexibility in RNA Binding

PLoS ONE ◽  
2012 ◽  
Vol 7 (1) ◽  
pp. e30038 ◽  
Author(s):  
Bogdan Tarus ◽  
Christophe Chevalier ◽  
Charles-Adrien Richard ◽  
Bernard Delmas ◽  
Carmelo Di Primo ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Influenza A Virus ◽  
Influenza A ◽  
Rna Binding ◽  
Protein Flexibility

scholarly journals Immunogenicity and Protection Efficacy of Replication-Deficient Influenza A Viruses with Altered NS1 Genes

2004 ◽  
Vol 78 (23) ◽  
pp. 13037-13045 ◽  
Author(s):  
Boris Ferko ◽  
Jana Stasakova ◽  
Julia Romanova ◽  
Christian Kittel ◽  
Sabine Sereinig ◽  
...  
Keyword(s):  
Influenza A ◽  
Rna Binding ◽  
T Cell Response ◽  
Binding Domain ◽  
Wild Type Virus ◽  
Type Virus ◽  
Ns1 Protein ◽  
Wild Type ◽  
Influenza A Viruses ◽  
Rna Binding Domain

ABSTRACT We explored the immunogenic properties of influenza A viruses with altered NS1 genes (NS1 mutant viruses). NS1 mutant viruses expressing NS1 proteins with an impaired RNA-binding function or insertion of a longer foreign sequence did not replicate in murine lungs but still were capable of inducing a Th1-type immune response resulting in significant titers of virus-specific serum and mucosal immunoglobulin G2 (IgG2) and IgA, but with lower titers of IgG1. In contrast, replicating viruses elicited high titers of serum and mucosal IgG1 but less serum IgA. Replication-deficient NS1 mutant viruses induced a rapid local release of proinflammatory cytokines such as interleukin-1β (IL-1β) and IL-6. Moreover, these viruses also elicited markedly higher levels of IFN-α/β in serum than the wild-type virus. Comparable numbers of virus-specific primary CD8+ T cells were determined in all of the groups of immunized mice. The most rapid onset of the recall CD8+-T-cell response upon the wild-type virus challenge was detected in mice primed with NS1 mutant viruses eliciting high levels of cytokines. It is noteworthy that there was one NS1 mutant virus encoding NS1 protein with a deletion of 40 amino acids predominantly in the RNA-binding domain that induced the highest levels of IFN-α/β, IL-6 and IL-1β after infection. Mice that were immunized with this virus were completely protected from the challenge infection. These findings indicate that a targeted modification of the RNA-binding domain of the NS1 protein is a valuable technique to generate replication-deficient, but immunogenic influenza virus vaccines.

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