Interaction between SARS-CoV-2 and Host Innate Immunity

DUAN Xiao-qiong, XIE He, CHEN Li-min

Abstract

Coronavirus disease 2019 (COVID-19), an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a global pandemic since its outbreak in 2019, presenting serious threats to public health and the health of the people. As one of the main components of the host innate immune system, type-Ⅰ interferon (IFN) plays a critical role in the defense against viral infections. The battle between the virus and the host innate immune system determines the disease progression. It has been reported that SARS-CoV-2 inhibits IFN production and suppresses the activation of IFN signaling pathway through its interactions with the host innate immune system. Then, the weakened or delayed response of type-Ⅰ interferon causes the disturbance of host immune responses, which is one of the important reasons why SARS-CoV-2 causes such high morbidity and mortality. Herein, we reviewed and discussed the interaction between SARS-CoV-2 viral proteins and the host innate immune system, especially the interaction with type-Ⅰ IFN pathway, to provide new insights into the mechanisms of viral evasion of host immune response and new perspectives and strategies for treating COVID-19 with IFN.

 

Keywords: SARS-CoV-2, Viral proteins, IFN pathway, Virus-host interaction

 

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References


LIU S, CAI X, WU J, et al. Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation. Science, 2015, 347(6227): aaa2630[2021-08-15]. https://www.science. org/doi/10.1126/science.aaa2630.

AMOR S, FERNÁNDEZ BLANCO L, BAKER D. Innate immunity during SARS‐CoV‐2: evasion strategies and activation trigger hypoxia and vascular damage. Clin Exp Immunol,2020,202(2): 193–209.

SA RIBERO M, JOUVENET N, DREUX M, et al. Interplay between SARS-CoV-2 and the type I interferon response. PLoS Pathog, 2020, 16(7): e1008737[2021-08-15]. https://doi.org/10.1371/journal. ppat.1008737.

SHEMESH M, AKTEPE T E, DEERAIN J M, et al. SARS-CoV-2 suppresses IFNβ production mediated by NSP1, 5, 6, 15, ORF6 and ORF7b but does not suppress the effects of added interferon. PLoS Pathog, 2021, 17(8): e1009800[2021-08-15]. https://doi.org/10. 1371/journal.ppat.1009800.

BLANCO-MELO D, NILSSON-PAYANT B E, LIU W C, et al. Imbalanced host response to SARS-CoV-2 drives development of COVID-19. Cell, 2020, 181(5): 1036–1045. e9[2021-08-15]. https://doi.org/10.1016/j.cell.2020.04.026.

WU J, SHI Y, PAN X, et al. SARS-CoV-2 ORF9b inhibits RIG-I-MAVS antiviral signaling by interrupting K63-linked ubiquitination of NEMO. Cell Rep, 2021, 34(7): 108761[2021-08-15]. https://doi.org/10. 1016/j.celrep.2021.108761.

YIN X, RIVA L, PU Y, et al. MDA5 governs the innate immune response to SARS-CoV-2 in lung epithelial cells. Cell Rep, 2021, 34(2): 108628[2021-08-15]. https://doi.org/10.1016/j.celrep.2020.108628.

FAJGENBAUM D C, JUNE C H. Cytokine storm. N Engl J Med,2020, 383(23): 2255–2273.

HADJADJ J, YATIM N, BARNABEI L, et al. Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients. Science,2020,369(6504): 718–724.

V’KOVSKI P, KRATZEL A, STEINER S, et al. Coronavirus biology and replication: Implications for SARS-CoV-2. Nat Rev Microbiol,2021,19(3): 155–170.

FELGENHAUER U, SCHOEN A, GAD H H, et al. Inhibition of SARS–CoV-2 by type I and type Ⅲ interferons. J Biol Chem,2020, 295(41): 13958–13964.

GORDON D E, JANG G M, BOUHADDOU M, et al. A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature, 2020,583(7816): 459–468.

YUEN C K, LAM J Y, WONG W M, et al. SARS-CoV-2 NSP13, NSP14, NSP15 AND ORF6 function as potent interferon antagonists. Emerg Microbes Infect,2020,9(1): 1418–1428.

LEI X, DONG X, MA R, et al. Activation and evasion of type Ⅰ interferon responses by SARS-CoV-2. Nat Commun, 2020, 11(1): 3810[2021-08-15]. https://doi.org/10.1038/s41467-020-17665-9.

XIA H, CAO Z, XIE X, et al. Evasion of type Ⅰ interferon by SARS-CoV-2. Cell Rep, 2020, 33(1): 108234[2021-08-15]. https://doi.org/ 10.1016/j.celrep.2020.108234.

HAYN M, HIRSCHENBERGER M, KOEPKE L, et al. Systematic functional analysis of SARS-CoV-2 proteins uncovers viral innate immune antagonists and remaining vulnerabilities. Cell Rep, 2021, 35(7): 109126[2021-08-15]. https://doi.org/10.1016/j.celrep.2021.109126.

BANERJEE A K, BLANCO M R, BRUCE E A, et al. SARS-CoV-2 disrupts splicing, translation, and protein trafficking to suppress host defenses. Cell, 2020, 183(5): 1325–1339. e21[2021-08-15]. https://doi.org/10.1016/j.cell.2020.10.004.

THOMS M, BUSCHAUER R, AMEISMEIER M, et al. Structural basis for translational shutdown and immune evasion by the Nsp1 protein of SARS-CoV-2. Science,2020,369(6508): 1249–1255.

SCHUBERT K, KAROUSIS E D, JOMAA A, et al. SARS-CoV-2 Nsp1 binds the ribosomal mRNA channel to inhibit translation. Nat Struct Mol Biol,2020,27(10): 959–966.

KUMAR A, ISHIDA R, STRILETS T, et al. SARS-CoV-2 nonstructural protein 1 inhibits the interferon response by causing depletion of key host signaling factors. J Virol, 2021, 95(13): e0026621[2021-08-15]. https://doi.org/10.1128/JVI.00266-21.

LAPOINTE C P, GROSELY R, JOHNSON A G, et al. Dynamic competition between SARS-CoV-2 NSP1 and mRNA on the human ribosome inhibits translation initiation. Proc Natl Acad Sci U S A, 2021, 118(6): e2017715118[2021-08-15]. https://doi.org/10.1073/pnas. 2017715118.

HSU J C C, LAURENT-ROLLE M, PAWLAK J B, et al. Translational shutdown and evasion of the innate immune response by SARS-CoV-2 NSP14 protein. Proc Natl Acad Sci U S A, 2021, 118(24): e2101161118 [2021-08-15]. https://doi.org/10.1073/pnas.2101161118.

FAN J B, ARIMOTO K, MOTAMEDCHABOKI K, et al. Identification and characterization of a novel ISG15-ubiquitin mixed chain and its role in regulating protein homeostasis. Sci Rep, 2015, 5: 12704[2021-08-15]. https://www.nature.com/articles/srep12704. doi: 10.1038/srep12704.

KLEMM T, EBERT G, CALLEJA D J, et al. Mechanism and inhibition of the papain‐like protease, PLpro, of SARS‐CoV‐2. EMBO J, 2020,39(18): e106275[2021-08-15]. https://doi.org/10.15252/embj.2020106275.

SHIN D, MUKHERJEE R, GREWE D, et al. Papain-like protease regulates SARS-CoV-2 viral spread and innate immunity. Nature,2020, 587(7835): 657–662.

MOUSTAQIL M, OLLIVIER E, CHIU H P, et al. SARS-CoV-2 proteases PLpro and 3CLpro cleave IRF3 and critical modulators of inflammatory pathways (NLRP12 and TAB1): implications for disease presentation across species. Emerg Microbes Infect,2021,10(1): 178–195.

RUSSO L C, TOMASIN R, MATOS I A, et al. The SARS-CoV-2 Nsp3 macrodomain reverses PARP9/DTX3L-dependent ADP-ribosylation induced by interferon signalling. J Biol Chem, 2021, 297(3): 10104[2021-08-15]. https://doi.org/10.1016/j.jbc.2021.101041.

CLAVERIE J M. A putative role of de-mono-ADP-ribosylation of STAT1 by the SARS-CoV-2 Nsp3 protein in the cytokine storm syndrome of COVID-19. Viruses, 2020, 12(6): 646[2021-08-15]. https://doi.org/ 10.3390/v12060646.

WU Y, MA L, ZHUANG Z, et al. Main protease of SARS-CoV-2 serves as a bifunctional molecule in restricting type Ⅰ interferon antiviral signaling. Signal Transduct Target Ther, 2020, 5(1): 221[2021-08-15]. https://doi.org/10.1038/s41392-020-00332-2.

GORI SAVELLINI G, ANICHINI G, GANDOLFO C, et al. SARS-CoV-2 N protein targets TRIM25-mediated RIG-Ⅰ activation to suppress innate immunity. Viruses, 2021, 13(8): 1439: [2021-08-15]. https://doi.org/ 10.3390/v13081439.

ZHAO Y, SUI L, WU P, et al. A dual-role of SARS-CoV-2 nucleocapsid protein in regulating innate immune response. Signal Transduct Target Ther, 2021, 6(1): 331[2021-08-15]. https://doi.org/10.1038/s41392-021-00742-w.

LI J Y, LIAO C H, WANG Q, et al. The ORF6, ORF8 and nucleocapsid proteins of SARS-CoV-2 inhibit type Ⅰ interferon signaling pathway. Virus Res, 2020, 286: 198074[2021-08-15]. https://doi.org/10. 1016/j.virusres.2020.198074.

CHEN K, XIAO F, HU D, et al. SARS-CoV-2 nucleocapsid protein interacts with RIG-Ⅰ and represses RIG-mediated IFN-β production. Viruses, 2021, 13(1): 47[2021-08-15]. https://doi.org/10.3390/v13010047.

MIORIN L, KEHRER T, SANCHEZ-APARICIO M T, et al. SARS-CoV-2 Orf6 hijacks Nup98 to block STAT nuclear import and antagonize interferon signaling. Proc Natl Acad Sci U S A,2020,117(45): 28344–28354.


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