scholarly journals Structure and Function of the NS1 Protein of Influenza A Virus

2007 ◽  
Vol 39 (3) ◽  
pp. 155-162 ◽  
Author(s):  
Dongzi LIN ◽  
Jingfang LAN ◽  
Zhizhen ZHANG
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Structure And Function ◽  
Ns1 Protein ◽  
And Function

scholarly journals Effects of single-point amino acid substitutions on the structure and function neuraminidase proteins in influenza A virus

2008 ◽  
Vol 52 (4) ◽  
pp. 216-223 ◽  
Author(s):  
Takuya Yano ◽  
Eri Nobusawa ◽  
Alexander Nagy ◽  
Setsuko Nakajima ◽  
Katsuhisa Nakajima
Keyword(s):  
Amino Acid ◽  
Influenza A Virus ◽  
Influenza A ◽  
Single Point ◽  
Structure And Function ◽  
Amino Acid Substitutions ◽  
And Function

scholarly journals Targeting Hemagglutinin: Approaches for Broad Protection against the Influenza A Virus

Viruses ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 405 ◽  
Author(s):  
Zhang ◽  
Xu ◽  
Zhang ◽  
Liu ◽  
Xue ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Protective Efficacy ◽  
Structure And Function ◽  
Antigenic Drift ◽  
Influenza A Viruses ◽  
Universal Vaccine ◽  
Vaccine Candidates ◽  
And Function ◽  
Ha Protein

Influenza A viruses are dynamically epidemic and genetically diverse. Due to the antigenic drift and shift of the virus, seasonal vaccines are required to be reformulated annually to match with current circulating strains. However, the mismatch between vaccinal strains and circulating strains occurs frequently, resulting in the low efficacy of seasonal vaccines. Therefore, several “universal” vaccine candidates based on the structure and function of the hemagglutinin (HA) protein have been developed to meet the requirement of a broad protection against homo-/heterosubtypic challenges. Here, we review recent novel constructs and discuss several important findings regarding the broad protective efficacy of HA-based universal vaccines.

scholarly journals Development of an HTS Assay for the Search of Anti-influenza Agents Targeting the Interaction of Viral RNA with the NS1 Protein

2008 ◽  
Vol 13 (7) ◽  
pp. 581-590 ◽  
Author(s):  
Marta Maroto ◽  
Yolanda Fernandez ◽  
Juan Ortin ◽  
Fernando Pelaez ◽  
M. Angerles Cabello
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Cytopathic Effect ◽  
Nonstructural Protein ◽  
Specific Interaction ◽  
Chemical Compounds ◽  
Viral Rna ◽  
Ns1 Protein ◽  
Rna Molecules ◽  
Novel Target

The NS1 protein is a nonstructural protein encoded by the influenza A virus. It is responsible for many alterations produced in the cellular metabolism upon infection by the virus and for modulation of virus virulence. The NS1 protein is able to perform a large variety of functions due to its ability to bind various types of RNA molecules, from both viral and nonviral origin, and to interact with several cell factors. With the aim of exploring whether the binding of NS1 protein to viral RNA (vRNA) could constitute a novel target for the search of anti-influenza drugs, a filter-binding assay measuring the specific interaction between the recombinant His-NS1 protein from influenza A virus and a radiolabeled model vRNA ( 32P-vNSZ) was adapted to a format suitable for screening and easy automation. Flashplate® technology (PerkinElmer, Waltham, MA), either in 96- or 384-well plates, was used. The Flashplate® wells were precoated with the recombinant His-NS1 protein, and the binding of His-NS1 to a 35S-vNSZ probe was measured. A pilot screening of a collection of 27,520 mixtures of synthetic chemical compounds was run for inhibitors of NS1 binding to vRNA. We found 3 compounds in which the inhibition of NS1 binding to vRNA, observed at submicromolar concentrations, was correlated with a reduction of the cytopathic effect during the infection of cell cultures with influenza virus. These results support the hypothesis that the binding of NS1 to vRNA could be a novel target for the development of anti-influenza drugs. ( Journal of Biomolecular Screening 2008:581-590)

scholarly journals Nuclear Translocation of Crk Adaptor Proteins by the Influenza A Virus NS1 Protein

Viruses ◽  
2016 ◽  
Vol 8 (4) ◽  
pp. 101 ◽  
Author(s):  
Leena Ylösmäki ◽  
Riku Fagerlund ◽  
Inka Kuisma ◽  
Ilkka Julkunen ◽  
Kalle Saksela
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Nuclear Translocation ◽  
Adaptor Proteins ◽  
Ns1 Protein

scholarly journals Unexpected Functional Divergence of Bat Influenza Virus NS1 Proteins

2017 ◽  
Vol 92 (5) ◽  
Author(s):  
Hannah L. Turkington ◽  
Mindaugas Juozapaitis ◽  
Nikos Tsolakos ◽  
Eugenia Corrales-Aguilar ◽  
Martin Schwemmle ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Virulence Factor ◽  
Influenza A ◽  
Nonstructural Protein ◽  
Functional Divergence ◽  
Protein A ◽  
Regulatory Subunit ◽  
Ns1 Protein ◽  
Influenza A Viruses ◽  
Hydrophobic Patch

ABSTRACT Recently, two influenza A virus (FLUAV) genomes were identified in Central and South American bats. These sequences exhibit notable divergence from classical FLUAV counterparts, and functionally, bat FLUAV glycoproteins lack canonical receptor binding and destroying activity. Nevertheless, other features that distinguish these viruses from classical FLUAVs have yet to be explored. Here, we studied the viral nonstructural protein NS1, a virulence factor that modulates host signaling to promote efficient propagation. Like all FLUAV NS1 proteins, bat FLUAV NS1s bind double-stranded RNA and act as interferon antagonists. Unexpectedly, we found that bat FLUAV NS1s are unique in being unable to bind host p85β, a regulatory subunit of the cellular metabolism-regulating enzyme, phosphoinositide 3-kinase (PI3K). Furthermore, neither bat FLUAV NS1 alone nor infection with a chimeric bat FLUAV efficiently activates Akt, a PI3K effector. Structure-guided mutagenesis revealed that the bat FLUAV NS1-p85β interaction can be reengineered (in a strain-specific manner) by changing two to four NS1 residues (96L, 99M, 100I, and 145T), thereby creating a hydrophobic patch. Notably, ameliorated p85β-binding is insufficient for bat FLUAV NS1 to activate PI3K, and a chimeric bat FLUAV expressing NS1 with engineered hydrophobic patch mutations exhibits cell-type-dependent, but species-independent, propagation phenotypes. We hypothesize that bat FLUAV hijacking of PI3K in the natural bat host has been selected against, perhaps because genes in this metabolic pathway were differentially shaped by evolution to suit the unique energy use strategies of this flying mammal. These data expand our understanding of the enigmatic functional divergence between bat FLUAVs and classical mammalian and avian FLUAVs. IMPORTANCE The potential for novel influenza A viruses to establish infections in humans from animals is a source of continuous concern due to possible severe outbreaks or pandemics. The recent discovery of influenza A-like viruses in bats has raised questions over whether these entities could be a threat to humans. Understanding unique properties of the newly described bat influenza A-like viruses, such as their mechanisms to infect cells or how they manipulate host functions, is critical to assess their likelihood of causing disease. Here, we characterized the bat influenza A-like virus NS1 protein, a key virulence factor, and found unexpected functional divergence of this protein from counterparts in other influenza A viruses. Our study dissects the molecular changes required by bat influenza A-like virus NS1 to adopt classical influenza A virus properties and suggests consequences of bat influenza A-like virus infection, potential future evolutionary trajectories, and intriguing virus-host biology in bat species.

Role of the chaperone protein 14-3-3ε in the regulation of influenza A virus-activated beta interferon

2021 ◽  
Author(s):  
Ee-Hong Tam ◽  
Yen-Chin Liu ◽  
Chian-Huey Woung ◽  
Helene Minyi Liu ◽  
Guan-Hong Wu ◽  
...  
Keyword(s):  
Virus Infection ◽  
Influenza A Virus ◽  
Influenza A ◽  
Critical Role ◽  
Type I ◽  
Type I Ifn ◽  
Ns1 Protein ◽  
Chaperone Protein ◽  
Influenza A Virus Infection

The NS1 protein of the influenza A virus plays a critical role in regulating several biological processes in cells, including the type I interferon (IFN) response. We previously profiled the cellular factors that interact with the NS1 protein of influenza A virus and found that the NS1 protein interacts with proteins involved in RNA splicing/processing, cell cycle regulation, and protein targeting processes, including 14-3-3ε. Since 14-3-3ε plays an important role in RIG-I translocation to MAVS to activate type I IFN expression, the interaction of the NS1 and 14-3-3ε proteins may prevent the RIG-I-mediated IFN response. In this study, we confirmed that the 14-3-3ε protein interacts with the N-terminal domain of the NS1 protein and that the NS1 protein inhibits RIG-I-mediated IFN-β promoter activation in 14-3-3ε-overexpressing cells. In addition, our results showed that knocking down 14-3-3ε can reduce IFN-β expression elicited by influenza A virus and enhance viral replication. Furthermore, we found that threonine in the 49 th amino acid position of the NS1 protein plays a role in the interaction with 14-3-3ε. Influenza A virus expressing C-terminus-truncated NS1 with T49A mutation dramatically increases IFN-β mRNA in infected cells and causes slower replication than that of virus without the T-to-A mutation. Collectively, this study demonstrates that 14-3-3ε is involved in influenza A virus-initiated IFN-β expression and that the interaction of the NS1 protein and 14-3-3ε may be one of the mechanisms for inhibiting type I IFN activation during influenza A virus infection. IMPORTANCE Influenza A virus is an important human pathogen causing severe respiratory disease. The virus has evolved several strategies to dysregulate the innate immune response and facilitate its replication. We demonstrate that the NS1 protein of influenza A virus interacts with the cellular chaperone protein 14-3-3ε, which plays a critical role in RIG-I translocation that induces type I IFN expression, and that NS1 protein prevents RIG-I translocation to mitochondrial membrane. The interaction site for 14-3-3ε is the RNA-binding domain (RBD) of the NS1 protein. Therefore, this research elucidates a novel mechanism by which the NS1 RBD mediates IFN-β suppression to facilitate influenza A viral replication. Additionally, the findings reveal the antiviral role of 14-3-3ε during influenza A virus infection.

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