Old dog, new tricks: Influenza A virus NS1 and in vitro fibrillogenesis

Shaldzhyan, Aram A.; Zabrodskaya, Yana A.; Baranovskaya, Irina; Sergeeva, Maria V.; Горшков, А. Н.; Savin, I.I.; Shishlyannikov, Sergey M.; Ramsay, Edward; Protasov, A. V.; Kukhareva, A.P.; Егоров, Владимир В.

doi:10.1016/j.biochi.2021.07.005

Cited by 6 publications

(7 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Influenza A non-structured protein 1 (NS1) is a 26 kD unstructured protein that suppresses the host cell immune response and hence increase the virulence of the virus. This protein can also from amyloid in vitro [ 89 ].…”

Section: Amyloidogenic Viral Proteinsmentioning

confidence: 99%

Viruses and amyloids - a vicious liaison

Hammarström

Nyström

2023

Prion

View full text Add to dashboard Cite

The crosstalk between viral infections, amyloid formation and neurodegeneration has been discussed with varying intensity since the last century. Several viral proteins are known to be amyloidogenic. Post-acute sequalae (PAS) of viral infections is known for several viruses. SARS-CoV-2 and COVID-19 implicate connections between amyloid formation and severe outcomes in the acute infection, PAS and neurodegenerative diseases. Is the amyloid connection causation or just correlation? In this review we highlight several aspects where amyloids and viruses meet. The evolutionary driving forces that dictate protein amyloid formation propensity are different for viruses compared to prokaryotes and eukaryotes, while posttranslational endoproteolysis appears to be a common mechanism leading up to amyloid formation for both viral and human proteins. Not only do human and viral proteins form amyloid irrespective of each other but there are also several examples of co-operativity between amyloids, viruses and the inter-, and intra-host spread of the respective entity. Abnormal blood clotting in severe and long COVID and as a side effect in some vaccine recipients has been connected to amyloid formation of both the human fibrin and the viral Spike-protein. We conclude that there are many intersects between viruses and amyloids and, consequently, amyloid and virus research need to join forces here. We emphasize the need to accelerate development and implementation in clinical practice of antiviral drugs to preclude PAS and downstream neurological damage. There is also an ample need for retake on suitable antigen targets for the further development of next generation of vaccines against the current and coming pandemics.

show abstract

Section: Amyloidogenic Viral Proteinsmentioning

confidence: 99%

Viruses and amyloids - a vicious liaison

Hammarström

Nyström

2023

Prion

View full text Add to dashboard Cite

show abstract

“…In experiments studying the biological activity of the NS1 protein of influenza A H1N1 strain that caused the pandemic of 1918, it was found that one of the peptides ( 140 rleylillraft 151 , G51 ), corresponding to the primary structure of the NS1 protein fragment of influenza A virus [20] and having the highest homology with the CP peptide among the proteins of influenza A virus, is capable of oligomerization and the formation of insoluble fibrillar aggregates in concentrations of 0.2-1 mM after incubation for 24 hours at 55ºC [24].…”

Section: Resultsmentioning

confidence: 99%

“…However, the sequence of the potential immunosuppressive domain of NS1, given in [20] corresponds to the core region of amyloid-like fibrils formed by the NS1 protein in vitro [24]. The presence of homology in the sequences of CP and the potential immunosuppressive domain, together with the ability of both peptides to form beta-structured oligomers, and in the case of NS1 fragment - amyloid-like fibrils, provides a basis for suggesting that such peptides may influence each other’s conformation by a prion-like mechanism.…”

Section: Introductionmentioning

confidence: 99%

How the immune mousetrap works: structural evidence for the immunomodulatory action of a peptide from influenza NS1 protein

Zabrodskaya,

Tsvetkov,

Shurygina

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

One of the critical stages of the T-cell immune response is the dimerization of the intramembrane domains of T-cell receptors (TCR). Structural similarities between the immunosuppressive domains of viral proteins and the transmembrane domains of TCR have led several authors to hypothesize the mechanism of immune response suppression by highly pathogenic viruses: viral proteins embed themselves in the membrane and act on the intramembrane domain of the TCRalpha subunit, hindering its functional oligomerization. It has also been suggested that this mechanism is used by influenza A virus in NS1-mediated immunosuppression. We have shown that the peptide corresponding to the primary structure of the potential immunosuppressive domain of NS1 protein (G51) can reduce concanavalin A-induced proliferation of PBMC cells, as well as in vitro, G51 can affect the oligomerization of the core peptide corresponding to the intramembrane domain of TCR, using AFM and small-angle neutron scattering.The results obtained usingin celluloandin vitromodel systems suggest the presence of functional interaction between the NS1 fragment and the intramembrane domain of the TCR alpha subunit. We have proposed a possible scheme for such interaction obtained by computer modeling.This suggests the existence of another NS1-mediated mechanism of immunosuppression in influenza.Abstract Figure

show abstract

“…At the same time, the presence of the NS1 protein in exosomes was indirectly shown earlier [57]. To perform its function, a sufficiently high concentration of exogenous NS1 in the extracellular environment is required, or it must act by inducing a conformational transition, as was previously suggested [72], but the transfer of NS1 from an infected cell to a healthy cell in the form of mRNA is not excluded either.…”

Section: Identification Of Viral Rna In Exosomesmentioning

confidence: 87%

Exosomes Released by Influenza-Virus-Infected Cells Carry Factors Capable of Suppressing Immune Defense Genes in Naïve Cells

Zabrodskaya

Plotnikova

Gavrilova

et al. 2022

Viruses

Self Cite

View full text Add to dashboard Cite

Exosomes are involved in intercellular communication and can transfer regulatory molecules between cells. Consequently, they can participate in host immune response regulation. For the influenza A virus (IAV), there is very limited information on changes in exosome composition during cell infection shedding light on the potential role of these extracellular membrane vesicles. Thus, the aim of our work was to study changes in exosomal composition following IAV infection of cells, as well as to evaluate their effect on uninfected cells. Methods: To characterize changes in the composition of cellular miRNAs and mRNAs of exosomes during IAV infection of A549 cells, NGS was used, as well as PCR to identify viral genes. Naïve A549 cells were stimulated with infected-cell-secreted exosomes for studying their activity. Changes in the expression of genes associated with the cell’s immune response were shown using PCR. The effect of exosomes on IAV replication was shown in MDCK cells using In-Cell ELISA and PCR of the supernatants. Results: A change in the miRNA composition (miR-21-3p, miR-26a-5p, miR-23a-5p, miR-548c-5p) and mRNA composition (RPL13A, MKNK2, TRIB3) of exosomes under the influence of the IAV was shown. Many RNAs were involved in the regulation of the immune response of the cell, mainly by suppressing it. After exosome stimulation of naïve cells, a significant decrease in the expression of genes involved in the immune response was shown (RIG1, IFIT1, MDA5, COX2, NFκB, AnxA1, PKR, IL6, IL18). When infecting MDCK cells, a significant decrease in nucleoprotein levels was observed in the presence of exosomes secreted by mock-infected cells. Viral levels in supernatants also decreased. Conclusions: Exosomes secreted by IAV-infected cells could reduce the immune response of neighboring intact cells, leading to more effective IAV replication. This may be associated both with regulatory functions of cellular miRNAs and mRNAs carried by exosomes, or with the presence of viral mRNAs encoding proteins with an immunosuppressive function.

show abstract

Old dog, new tricks: Influenza A virus NS1 and in vitro fibrillogenesis

Cited by 6 publications

References 24 publications

Viruses and amyloids - a vicious liaison

Viruses and amyloids - a vicious liaison

How the immune mousetrap works: structural evidence for the immunomodulatory action of a peptide from influenza NS1 protein

Exosomes Released by Influenza-Virus-Infected Cells Carry Factors Capable of Suppressing Immune Defense Genes in Naïve Cells

Contact Info

Product

Resources

About