2'-5'-Oligoadenylates as a «tool» of innate immunity

Tkachuk, Z. Yu.

doi:10.7124/bc.000821

Cited by 5 publications

(3 citation statements)

References 35 publications

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“…Activation of the classical OAS/RNase L pathway results in degradation of both viral and cellular RNA including ribosomal RNA of infected cells. Thereafter, the protein translation is inhibited in these cells and viral replication is effectively prevented (Silverman, 2007;Tkachuk, 2013).…”

Section: Introductionmentioning

confidence: 99%

Functional analysis of duck, goose, and ostrich 2′-5′-oligoadenylate synthetase

Tag-EL-Din-Hassan

Morimatsu

Agui

2018

Infection, Genetics and Evolution

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Up-to-date the flavivirus infection in avian taxa is not clearly defined. Several reports have demonstrated that many viruses belonging to Flaviviridae may cause diseases in poultry species; however, the susceptibility of other avian species is variable and still unclear. In human and mice, the 2'-5'-oligoadenylate synthetase (OAS) proteins are associated with resistance to the flavivirus infection as well as other virus infections. However, the avian OAS proteins are rarely studied. In our previous studies, we confirmed that the chicken OAS-like protein (chOASL) expressed OAS-enzymatic activity (the classical OAS/RNase L-dependent pathway) as well as the anti-flavivirus activity (the putative OAS/RNase L-independent pathway). Therefore, the current study aimed at functional analysis of avian OAS proteins from duck, goose, and ostrich. The duOASL, goOASL, and osOAS1 proteins expressed enzymatic activity as well as chOASL, whereas osOASL expressed little enzymatic activity. On the other hand, duOASL, goOASL, and osOASL possessed significant antiviral activity against West Nile virus (WNV)-replicon replication as well as chOASL, whereas osOAS1 did not. In addition, similar to chOASL, their antiviral activity was independent of RNase L activation. These results suggest that OASL is the only OAS protein in the duck and goose as well as chicken and possesses both OAS-enzymatic and anti-flavivirus activities, whereas the ostrich possesses both OAS1 and OASL proteins with sharing the functional activities, OAS-enzymatic and anti-flavivirus activities, respectively. It is of interest that the ostrich undergoes differential process in OAS gene evolution from other poultries and thus possesses different molecular mechanism in antiviral activity.

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Section: Introductionmentioning

confidence: 99%

Functional analysis of duck, goose, and ostrich 2′-5′-oligoadenylate synthetase

Tag-EL-Din-Hassan

Morimatsu

Agui

2018

Infection, Genetics and Evolution

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“…2′-5′-Oligoadenylates (2′-5′-As) have a wide spectrum of antiviral action. They affect proteins of 2′-5′-oligoadenylate synthetase (OAS)/RNase L pathway and this manner lead to the destruction of viral RNA [ 31 ]. The 2′-5′-As can bind to the proteins of signaling pathways of innate immunity such as interferon-α, S100 calcium-binding protein A1 (S100A1) with relatively weak (micromolar) dissociation constant and change conformation of these proteins by affecting their secondary structures [ 10 , 11 ].…”

Section: Discussionmentioning

confidence: 99%

Complexes of Oligoribonucleotides with D-Mannitol Inhibit Hemagglutinin–Glycan Interaction and Suppress Influenza A Virus H1N1 (A/FM/1/47) Infectivity In Vitro

2017

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The influenza virus hemagglutinin (HA) mediates both receptor (glycan) binding and membrane fusion for cell entry and has been the basis for subtyping influenza viruses. The oligoribonucleotides-d-mannitol (ORNs-d-M) complexes possess an anti-influenza activity in vitro and in vivo. In the present studies, we have found that ORNs-d-M interferes with hemagglutinin (HA)–glycan interaction and suppress viral infection in host cells. HA–glycan interactions were evaluated to indirectly quantify the amount of influenza virus titer by an agglutination assay. Influenza virus infectivity was determined by TCID50 assay. The direct virucidal action of the complexes was evaluated by both cytopathic effects (CPE) reduction assay and cell MTT assay. We found that ORNs-d-M hinders interaction between HA and glycan. These complexes decreased the infectivity of influenza virus and had a direct virucidal action. ORNs-d-M reduces influenza virus infectivity, affecting the HA–glycan interaction in vitro. By suppressing the influenza viral infection, the ORNs-d-M can have direct virucidal action.

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“…Олігонуклеотидні противірусні препарати активно застосовуються в медицині протягом останніх десятиліть, проте молекулярний механізм їх дії залишається неясним. Як було показано в нашій попередній роботі, поєднання олігорибонуклеотидів (ОРН) з алкогольним цукром D-манітолом призводить до змін їх біологічної активності та ефективності (Tkachuk, 2013).…”

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Influence of oligoribonucleotides on the conformation and stability of interferon

Nikolaiev¹,

Vivcharyk²,

Chernykh³

et al. 2020

Visn. ukr. tov. genet. sel.

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Aim. To study the ability of yeast RNA oligoribonucleotides (ORNs) and their complexes withD-mannitol to influence the conformation and thermal stability of interferon (INF) α-2b. Methods. The ability of oligoribonucleotide drugs to bind to INF α-2b was studied using its fluorescence quenching method. The effect of ORN drugs on protein stability was studied by analyzing the thermal stability of INF. To confirm their influence on the conformation of the INF, we investigated the spectra of circular dichroism. Results. The ORN complexes with D-mannitol, due to their better protein binding, have been shown to have a much higher effect on the conformation and thermal stability of interferon α-2b than ORN. ORNs and their complexes with D-mannitol also increase the thermal stabilization of interferon. The addition of ORN and ORN with D-mannitol to INF leads to a decrease in the content of α-helical components in the protein structure and an increase in β-components and unstructured parts of the protein molecule. Addition of the ORN complex: D-mannitol, unlike the ORN, changes the architecture of the tertiary INF structure. Conclusions. Therefore, the ORN complexes with D-mannitol have a much higher effect on the conformation and thermal stability of interferon α-2b than the parent drug ORN. The more specific binding of oligonucleotides can probably explain this in the presence of mannitol to the protein. ORNs and ORN complexes with D-mannitol also increase the thermal stabilization of interferon by 2 and 1.8 °C, respectively. The addition of ORNs and ORN complexes with D-mannitol leads to a decrease in the content of α- helical components in the protein structure and an increase in antiparallel β-sheets, β-turns, and unstructured elements. In the presence of mannitol in the ORN molecule, the structure of INF changes more intensively. Addition of ORN complexes: D-mannitol to INF, unlike ORN, changes the architecture of the tertiary protein structure from a 2-layer sandwich to an alpha-beta complex.Keywords: oligonucleotides; interferon; mannitol; secondary protein structure.

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2'-5'-Oligoadenylates as a «tool» of innate immunity

Cited by 5 publications

References 35 publications

Functional analysis of duck, goose, and ostrich 2′-5′-oligoadenylate synthetase

Functional analysis of duck, goose, and ostrich 2′-5′-oligoadenylate synthetase

Complexes of Oligoribonucleotides with D-Mannitol Inhibit Hemagglutinin–Glycan Interaction and Suppress Influenza A Virus H1N1 (A/FM/1/47) Infectivity In Vitro

Influence of oligoribonucleotides on the conformation and stability of interferon

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