Immune evasion of SARS-CoV-2 from interferon antiviral system

Min, Yuan-Qin; Huang, Mengzhuo; Sun, Xiulian; Deng, Fei; Wang, Hualin; Ning, Yun‐Jia

doi:10.1016/j.csbj.2021.07.023

Cited by 58 publications

(64 citation statements)

References 92 publications

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“…However, in Poly(I:C)-treated mice, a marked reduction in both antigen intensity and number of positive cells at 0 and 6 hpi was observed (SARS-CoV-2 labeling and semiquantitative analysis; Figure 3i-k, respectively). In the brains of infected untreated mice, a very mild pathology was observed, including gliosis and demyelination (vacuolization in the white matter) in the affected regions (H&E staining; Figure 3m) as previously reported [37]. However, extensive labeling of SARS-CoV-2 was observed in all examined infected untreated mice (n = 5) throughout the brain, including the striatum, hippocampus, midbrain and cerebellum in the neurons and their processes (Figure 3r and Supplementary Figure S2).…”

Section: Poly(i:c) Treatment Reduces Viral Loads In Nasal Turbinates Lungs and Brainssupporting

confidence: 83%

“…In view of the reported immune subversion effects caused by SARS-CoV-2 [37] and the role of Poly(I:C) as an immune modulator, we aimed to characterize the inflammatory response induced by SARS-CoV-2 and the beneficial outcome of Poly(I:C) treatment by following the expression of 44 selected inflammatory-related genes. Lung and brain tissues were removed at 2 and 5 dpi, and the inflammatory-related gene expression profiles were analyzed by qRT-PCR.…”

Section: Effect Of Poly(i:c) Treatment On the Innate Immune Response Following Sars-cov-2 Infectionmentioning

confidence: 99%

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Induction of Innate Immune Response by TLR3 Agonist Protects Mice against SARS-CoV-2 Infection

Tamir

Melamed

Erez

et al. 2022

Viruses

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SARS-CoV-2, a member of the coronavirus family, is the causative agent of the COVID-19 pandemic. Currently, there is still an urgent need in developing an efficient therapeutic intervention. In this study, we aimed at evaluating the therapeutic effect of a single intranasal treatment of the TLR3/MDA5 synthetic agonist Poly(I:C) against a lethal dose of SARS-CoV-2 in K18-hACE2 transgenic mice. We demonstrate here that early Poly(I:C) treatment acts synergistically with SARS-CoV-2 to induce an intense, immediate and transient upregulation of innate immunity-related genes in lungs. This effect is accompanied by viral load reduction, lung and brain cytokine storms prevention and increased levels of macrophages and NK cells, resulting in 83% mice survival, concomitantly with long-term immunization. Thus, priming the lung innate immunity by Poly(I:C) or alike may provide an immediate, efficient and safe protective measure against SARS-CoV-2 infection.

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Section: Poly(i:c) Treatment Reduces Viral Loads In Nasal Turbinates Lungs and Brainssupporting

confidence: 83%

Section: Effect Of Poly(i:c) Treatment On the Innate Immune Response Following Sars-cov-2 Infectionmentioning

confidence: 99%

Induction of Innate Immune Response by TLR3 Agonist Protects Mice against SARS-CoV-2 Infection

Tamir

Melamed

Erez

et al. 2022

Viruses

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“…The antiviral is based on IFN-I (particularly IFN- β and IFN- α ), and type III IFNs serve as a basic component of innate immune response and facilitate the development of adaptive immune response against viral infection [ 81 ]. This infection promotes low levels of antiviral cytokines IFN- α / β .…”

Section: Infection Mechanism Of Sars-cov-2mentioning

confidence: 99%

Immunogenic and reactogenic efficacy of Covaxin and Covishield: a comparative review

et al. 2022

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SARS-CoV-2 is an RNA virus that was identified for the first time in December 2019 in Wuhan, China. The World Health Organization (WHO) labeled the novel coronavirus (COVID-19) outbreak a worldwide pandemic on March 11, 2020, due to its widespread infectivity pattern. Because of the catastrophic COVID-19 outbreak, the development of safe and efficient vaccinations has become a key priority in every health sector throughout the globe. On the 13th of January 2021, the vaccination campaign against SARS-CoV-2 was launched in India and started the administration of two types of vaccines known as Covaxin and Covishield. Covishield is an adenovirus vector-based vaccine, and Covaxin was developed by a traditional method of vaccine formulation, which is composed of adjuvanted inactivated viral particles. Each vaccine’s utility or efficiency is determined by its formulation, adjuvants, and mode of action. The efficacy of the vaccination depends on numeral properties like generation antibodies, memory cells, and cell-mediated immunity. According to the third-phase experiment, Covishield showed effectiveness of nearly 90%, whereas Covaxin has an effectiveness of about 80%. Both vaccination formulations in India have so far demonstrated satisfactory efficacy against numerous mutant variants of SARS-CoV-2. The efficacy of Covishield may be diminished if the structure of spike (S) protein changes dramatically in the future. In this situation, Covaxin might be still effective for such variants owing to its ability to produce multiple antibodies against various epitopes. This study reviews the comparative immunogenic and therapeutic efficacy of Covaxin and Covishield and also discussed the probable vaccination challenges in upcoming days.

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“…Nsp1 is the N-terminal product of ORF1ab, cleaved by papain-like proteinase (PLpro) from the polyprotein, promoting host mRNA degradation, blocking translation, and interfering with the innate immune response [ 8 , 9 , 10 , 11 ]. It also binds with ribosomal subunits (40S), inserting its C-terminal region into the entrance position of the channel (ribosomal mRNA), blocking the translation of mRNA [ 12 ]. The shutdown of the translational process inhibits the innate immune response [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Emerging Mutations in Nsp1 of SARS-CoV-2 and Their Effect on the Structural Stability

et al. 2021

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The genome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) encodes 16 non-structural (Nsp) and 4 structural proteins. Among the Nsps, Nsp1 inhibits host gene expression and also evades the immune system. This protein has been proposed as a target for vaccine development and also for drug design. Owing to its important role, the current study aimed to identify mutations in Nsp1 and their effect on protein stability and flexibility. This is the first comprehensive study in which 295,000 complete genomes have been screened for mutations after alignment with the Wuhan-Hu-1 reference genome (Accession NC_045512), using the CoVsurver app. The sequences harbored 933 mutations in the entire coding region of Nsp1. The most frequently occurring mutation in the 180-amino-acid Nsp1 protein was R24C (n = 1122), followed by D75E (n = 890), D48G (n = 881), H110Y (n = 860), and D144A (n = 648). Among the 933 non-synonymous mutations, 529 exhibited a destabilizing effect. Similarly, a gain in flexibility was observed in 542 mutations. The majority of the most frequent mutations were detected in the loop regions. These findings imply that Nsp1 mutations might be useful to exploit SARS-CoV-2′s pathogenicity. Genomic sequencing of SARS-CoV-2 on a regular basis will further assist in analyzing variations among the drug targets and to test the diagnostic accuracy. This wide range of mutations and their effect on Nsp1’s stability may have some consequences for the host’s innate immune response to SARS-CoV-2 infection and also for the vaccines’ efficacy. Based on this mutational information, geographically strain-specific drugs, vaccines, and antibody combinations could be a useful strategy against SARS-CoV-2 infection.

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Immune evasion of SARS-CoV-2 from interferon antiviral system

Abstract: Graphical abstract

Cited by 58 publications

References 92 publications

Induction of Innate Immune Response by TLR3 Agonist Protects Mice against SARS-CoV-2 Infection

Induction of Innate Immune Response by TLR3 Agonist Protects Mice against SARS-CoV-2 Infection

Immunogenic and reactogenic efficacy of Covaxin and Covishield: a comparative review

Emerging Mutations in Nsp1 of SARS-CoV-2 and Their Effect on the Structural Stability

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