The Role of Coronavirus RNA-Processing Enzymes in Innate Immune Evasion

Viral RNA sensing triggers innate antiviral responses in humans by stimulating signaling pathways that include crucial antiviral genes such as interferon. RNA viruses have evolved strategies to inhibit or escape these mechanisms. Coronaviruses use multiple enzymes to synthesize, modify, and process their genomic RNA and sub-genomic RNAs. These include Nsp15 and Nsp16, whose respective roles in RNA capping and dsRNA degradation play a crucial role in coronavirus escape from immune surveillance. Evolutionary studies on coronaviruses demonstrate that genome expansion in Nidoviruses was promoted by the emergence of Nsp14-ExoN activity and led to the acquisition of Nsp15- and Nsp16-RNA-processing activities. In this review, we discuss the main RNA-sensing mechanisms in humans as well as recent structural, functional, and evolutionary insights into coronavirus Nsp15 and Nsp16 with a view to potential antiviral strategies.

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Borrelia burgdorferi Resistance to a Major Skin Antimicrobial Peptide Is Independent of Outer Surface Lipoprotein Content

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00558-09 ◽

2009 ◽

Vol 53 (10) ◽

pp. 4490-4494 ◽

Cited By ~ 8

Author(s):

Amit Sarkar ◽

Kit Tilly ◽

Philip Stewart ◽

Aaron Bestor ◽

James M. Battisti ◽

...

Keyword(s):

Borrelia Burgdorferi ◽

Antimicrobial Peptide ◽

Immune Evasion ◽

Essential Role ◽

Potential Role ◽

Innate Immune ◽

Initial Stage ◽

Mammalian Infection ◽

Innate Immune Evasion

ABSTRACT We hypothesize a potential role for Borrelia burgdorferi OspC in innate immune evasion at the initial stage of mammalian infection. We demonstrate that B. burgdorferi is resistant to high levels (>200 μg/ml) of cathelicidin and that this antimicrobial peptide exhibits limited binding to the spirochetal outer membrane, irrespective of OspC or other abundant surface lipoproteins. We conclude that the essential role of OspC is unrelated to resistance to this component of innate immunity.

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The Mga Regulon but Not Deoxyribonuclease Sda1 of Invasive M1T1 Group A Streptococcus Contributes toIn VivoSelection of CovRS Mutations and Resistance to Innate Immune Killing Mechanisms

Infection and Immunity ◽

10.1128/iai.00857-15 ◽

2015 ◽

Vol 83 (11) ◽

pp. 4293-4303 ◽

Cited By ~ 9

Author(s):

Guanghui Liu ◽

Wenchao Feng ◽

Dengfeng Li ◽

Mengyao Liu ◽

Daniel C. Nelson ◽

...

Keyword(s):

Group A Streptococcus ◽

Regulatory System ◽

Innate Immune ◽

M Protein ◽

Content Type ◽

Group A ◽

Innate Immune Evasion ◽

Selection Of

ABSTRACTInvasive M1T1 group AStreptococcus(GAS) can have a mutation in the regulatory system CovRS, and this mutation can render strains hypervirulent. Interestingly, via mechanisms that are not well understood, the host innate immune system's neutrophils select spontaneous M1T1 GAS CovRS hypervirulent mutants, thereby enhancing the pathogen's ability to evade immune killing. It has been reported that the DNase Sda1 is critical for the resistance of M1T1 strain 5448 to killing in human blood and provides pressure forin vivoselection of CovRS mutations. We reexamined the role of Sda1 in the selection of CovRS mutations and in GAS innate immune evasion. Deletion ofsda1or all DNase genes in M1T1 strain MGAS2221 did not alter emergence of CovRS mutants during murine infection. Deletion ofsda1in strain 5448 resulted in Δsda1mutants with (5448 Δsda1M+strain) and without (5448 Δsda1M−strain) M protein production. The 5448 Δsda1M+strain accumulated CovRS mutationsin vivoand resisted killing in the bloodstream, whereas the 5448 Δsda1M−strain lostin vivoselection of CovRS mutations and was sensitive to killing. The deletion ofemmand a spontaneous Mga mutation in MGAS2221 reduced and preventedin vivoselection for CovRS mutants, respectively. Thus, in contrast to previous reports, Sda1 is not critical forin vivoselection of invasive M1T1 CovRS mutants and GAS resistance to innate immune killing mechanisms. In contrast, M protein and other Mga-regulated proteins contribute to thein vivoselection of M1T1 GAS CovRS mutants. These findings advance the understanding of the progression of invasive M1T1 GAS infections.

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Unraveling the Underlying Interaction Mechanism Between Dabie bandavirus and Innate Immune Response

Frontiers in Immunology ◽

10.3389/fimmu.2021.676861 ◽

2021 ◽

Vol 12 ◽

Author(s):

Chuan-min Zhou ◽

Xue-jie Yu

Keyword(s):

Interaction Mechanism ◽

Innate Immune ◽

Type I ◽

Innate Immune Responses ◽

Structural Protein ◽

Antiviral Responses ◽

Host Virus Interactions ◽

Virus Interactions ◽

Severe Fever

The genus Bandavirus consists of seven tick-borne bunyaviruses, among which four are known to infect humans. Dabie bandavirus, severe fever with thrombocytopenia syndrome virus (SFTSV), poses serious threats to public health worldwide. SFTSV is a tick-borne virus mainly reported in China, South Korea, and Japan with a mortality rate of up to 30%. To date, most immunology-related studies focused on the antagonistic role of SFTSV non-structural protein (NSs) in sequestering RIG-I-like-receptors (RLRs)-mediated type I interferon (IFN) induction and type I IFN mediated signaling pathway. It is still elusive whether the interaction of SFTSV and other conserved innate immune responses exists. As of now, no specific vaccines or therapeutics are approved for SFTSV prevention or treatments respectively, in part due to a lack of comprehensive understanding of the molecular interactions occurring between SFTSV and hosts. Hence, it is necessary to fully understand the host-virus interactions including antiviral responses and viral evasion mechanisms. In this review, we highlight the recent progress in understanding the pathogenesis of SFTS and speculate underlying novel mechanisms in response to SFTSV infection.

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G3BP1 inhibits RNA virus replication by positively regulating RIG-I-mediated cellular antiviral response

Cell Death and Disease ◽

10.1038/s41419-019-2178-9 ◽

2019 ◽

Vol 10 (12) ◽

Cited By ~ 9

Author(s):

Wenping Yang ◽

Yi Ru ◽

Jingjing Ren ◽

Juncui Bai ◽

Junshu Wei ◽

...

Keyword(s):

Sendai Virus ◽

Rna Virus ◽

Innate Immune ◽

Positive Regulation ◽

Antiviral Responses ◽

Antiviral Genes ◽

Cellular Antiviral Response ◽

Vesicular Stomatitis ◽

Recognition Receptor ◽

Inducible Gene

AbstractRetinoic acid-inducible gene I (RIG-I) is a pattern recognition receptor and is involved in the innate immune response against RNA viruses infection. Here, we demonstrate that the Ras-GTPase-activating protein SH3-domain-binding protein 1 (G3BP1) serves as a positive regulator of the RIG-I-mediated signaling pathway. G3BP1-deficient cells inhibited RNA virus-triggered induction of downstream antiviral genes. Furthermore, we found that G3BP1 inhibited the replication of Sendai virus and vesicular stomatitis virus, indicating a positive regulation of G3BP1 to cellular antiviral responses. Mechanistically, G3BP1 formed a complex with RNF125 and RIG-I, leading to decreased RNF125 via its auto-ubiquitination; thus, promoting expression of RIG-I. Overall, the results suggest a novel mechanism for G3BP1 in the positive regulation of antiviral signaling mediated by RIG-I.

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Viruses Seen by Our Cells: The Role of Viral RNA Sensors

Journal of Immunology Research ◽

10.1155/2018/9480497 ◽

2018 ◽

Vol 2018 ◽

pp. 1-14 ◽

Cited By ~ 12

Author(s):

Elias A. Said ◽

Nicolas Tremblay ◽

Mohammed S. Al-Balushi ◽

Ali A. Al-Jabri ◽

Daniel Lamarre

Keyword(s):

Rna Viruses ◽

Innate Immune ◽

Rna Helicases ◽

Antiviral Responses ◽

Cytokines And Chemokines ◽

Rna Sensors ◽

Molecular Patterns ◽

Type 1 Interferons

The role of the innate immune response in detecting RNA viruses is crucial for the establishment of proper inflammatory and antiviral responses. Different receptors, known as pattern recognition receptors (PRRs), are present in the cytoplasm, endosomes, and on the cellular surface. These receptors have the capacity to sense the presence of viral nucleic acids as pathogen-associated molecular patterns (PAMPs). This recognition leads to the induction of type 1 interferons (IFNs) as well as inflammatory cytokines and chemokines. In this review, we provide an overview of the significant involvement of cellular RNA helicases and Toll-like receptors (TLRs) 3, 7, and 8 in antiviral immune defenses.

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Thioester-Containing Proteins in the Drosophila melanogaster Immune Response against the Pathogen Photorhabdus

Insects ◽

10.3390/insects11020085 ◽

2020 ◽

Vol 11 (2) ◽

pp. 85

Author(s):

Ioannis Eleftherianos ◽

Upasana Sachar

Keyword(s):

Drosophila Melanogaster ◽

Immune Surveillance ◽

Fruit Fly ◽

Research Field ◽

Innate Immune ◽

Host Immune System ◽

Innate Immune Signaling ◽

Microbe Interactions ◽

Host Microbe Interactions

The fruit fly Drosophila melanogaster forms a magnificent model for interpreting conserved host innate immune signaling and functional processes in response to microbial assaults. In the broad research field of host-microbe interactions, model hosts are used in conjunction with a variety of pathogenic microorganisms to disentangle host immune system activities and microbial pathogenicity strategies. The pathogen Photorhabdus is considered an established model for analyzing bacterial virulence and symbiosis due to its unique life cycle that extends between two invertebrate hosts: an insect and a parasitic nematode. In recent years, particular focus has been given to the mechanistic participation of the D. melanogaster thioester-containing proteins (TEPs) in the overall immune capacity of the fly upon response against the pathogen Photorhabdus alone or in combination with its specific nematode vector Heterorhabditis bacteriophora. The original role of certain TEPs in the insect innate immune machinery was linked to the antibacterial and antiparasite reaction of the mosquito malaria vector Anopheles gambiae; however, revamped interest in the immune competence of these molecules has recently emerged from the D. melanogaster-Photorhabdus infection system. Here, we review the latest findings on this topic with the expectation that such information will refine our understanding of the evolutionary immune role of TEPs in host immune surveillance.

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