Coronavirus infections and immune responses

Geng Li, Yaohua Fan, Yanni Lai, Tiantian Han, Zonghui Li, Peiwen Zhou, Pan Pan, Wenbiao Wang, Dingwen Hu, Xiaohong Liu, Qiwei Zhang, Jianguo Wu, Geng Li, Yaohua Fan, Yanni Lai, Tiantian Han, Zonghui Li, Peiwen Zhou, Pan Pan, Wenbiao Wang, Dingwen Hu, Xiaohong Liu, Qiwei Zhang, Jianguo Wu

Abstract

Coronaviruses (CoVs) are by far the largest group of known positive-sense RNA viruses having an extensive range of natural hosts. In the past few decades, newly evolved Coronaviruses have posed a global threat to public health. The immune response is essential to control and eliminate CoV infections, however, maladjusted immune responses may result in immunopathology and impaired pulmonary gas exchange. Gaining a deeper understanding of the interaction between Coronaviruses and the innate immune systems of the hosts may shed light on the development and persistence of inflammation in the lungs and hopefully can reduce the risk of lung inflammation caused by CoVs. In this review, we provide an update on CoV infections and relevant diseases, particularly the host defense against CoV-induced inflammation of lung tissue, as well as the role of the innate immune system in the pathogenesis and clinical treatment.

Keywords: chemokine; coronavirus; cytokines; inflammation; interferon.

Conflict of interest statement

The authors declare that there are no conflict of interests.

© 2020 Wiley Periodicals, Inc.

Figures

Figure 1
Figure 1
Coronavirus particle. Coronaviruses are enveloped, nonsegmented, positive‐sense single‐stranded RNA virus genomes in the size ranging from 26 to 32 kilobases. The virion has a nucleocapsid composed of genomic RNA and phosphorylated nucleocapsid (N) protein, which is buried inside phospholipid bilayers and covered by the spike glycoprotein trimmer (S). The membrane (M) protein (a type III transmembrane glycoprotein) and the envelope (E) protein are located among the S proteins in the virus envelope
Figure 2
Figure 2
The innate immune response and adaptive immune responses of Coronaviruses (CoV) infection during an infection. A, CoV infects macrophages, and then macrophages present CoV antigens to T cells. This process leads to T cell activation and differentiation, including the production of cytokines associated with the different T cell subsets (ie, Th17), followed by a massive release of cytokines for immune response amplification. The continued production of these mediators due to viral persistence has a negative effect on NK, and CD8 T cell activation. However, CD8 T cells produce very effective mediators to clear CoV. B, Attachment of CoV to DPP4R on the host cell through S protein leads to the appearance of genomic RNA in the cytoplasm. An immune response to dsRNA can be partially generated during CoV replication. TLR‐3 sensitized by dsRNA and cascades of signaling pathways (IRFs and NF‐κB activation, respectively) are activated to produce type I IFNs and proinflammatory cytokines. The production of type I IFNs is important to enhance the release of antiviral proteins for the protection of uninfected cells. Sometimes, accessory proteins of CoV can interfere with TLR‐3 signaling and bind the dsRNA of CoV during replication to prevent TLR‐3 activation and evade the immune response. TLR‐4 might recognize S protein and lead to the activation of proinflammatory cytokines through the MyD88‐dependent signaling pathway. Virus‐cell interactions lead to the strong production of immune mediators. The secretion of large quantities of chemokines and cytokines (IL‐1, IL‐6, IL‐8, IL‐21, TNF‐β, and MCP‐1) is promoted in infected cells in response to CoV infection. These chemokines and cytokines, in turn, recruit lymphocytes and leukocytes to the site of infection. Red lines refer to inhibitory effects. Green lines refer to activating effects

References

    1. World Health Organization . Laboratory testing of human suspected cases of novel coronavirus (nCoV) infection [published online ahead of print January 21, 2020].
    1. World Health Organization . Novel Coronavirus (2019‐nCoV) situation report‐2 [published online ahead of print January 21, 2020].
    1. World Health Organization . Middle East respiratory syndrome coronavirus (MERS‐CoV) [published online ahead of print January 21, 2020].
    1. World Health Organization . WHO MERS global summary and assessment of risk [published online ahead of print January 21, 2020].
    1. Koh D, Sng J. Lessons from the past: perspectives on severe acute respiratory syndrome. Asia Pac J Public Health. 2010;22(3 Suppl):132s‐136s.
    1. Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell. 2006;124(4):783‐801.
    1. Kawai T, Akira S. The role of pattern‐recognition receptors in innate immunity: update on Toll‐like receptors. Nature Immunol. 2010;11(5):373‐384.
    1. Pobezinskaya YL, Kim YS, Choksi S, et al. The function of TRADD in signaling through tumor necrosis factor receptor 1 and TRIF‐dependent Toll‐like receptors. Nature Immunol. 2008;9(9):1047‐1054.
    1. Ermolaeva MA, Michallet MC, Papadopoulou N, et al. Function of TRADD in tumor necrosis factor receptor 1 signaling and in TRIF‐dependent inflammatory responses. Nature Immunol. 2008;9(9):1037‐1046.
    1. Hacker H, Karin M. Regulation and function of IKK and IKK‐related kinases. Sci STKE. 2006;2006(357):re13.
    1. Häcker H, Redecke V, Blagoev B, et al. Specificity in Toll‐like receptor signalling through distinct effector functions of TRAF3 and TRAF6. Nature. 2006;439(7073):204‐207.
    1. Kell AM, Gale M Jr. RIG‐I in RNA virus recognition. Virology. 2015;479‐480:110‐121.
    1. Yoneyama M, Fujita T. RNA recognition and signal transduction by RIG‐I‐like receptors. Immunol Rev. 2009;227(1):54‐65.
    1. Yoneyama M, Onomoto K, Jogi M, Akaboshi T, Fujita T. Viral RNA detection by RIG‐I‐like receptors. Curr Opin Immunol. 2015;32:48‐53.
    1. Yoneyama M, Fujita T. Recognition of viral nucleic acids in innate immunity. Rev Med Virol. 2010;20(1):4‐22.
    1. Takeuchi O, Akira S. Pattern recognition receptors and inflammation. Cell. 2010;140(6):805‐820.
    1. Weber M, Gawanbacht A, Habjan M, et al. Incoming RNA virus nucleocapsids containing a 5′‐triphosphorylated genome activate RIG‐I and antiviral signaling. Cell Host Microbe. 2013;13(3):336‐346.
    1. Goubau D, Schlee M, Deddouche S, et al. Antiviral immunity via RIG‐I‐mediated recognition of RNA bearing 5'‐diphosphates. Nature. 2014;514(7522):372‐375.
    1. Civril F, Bennett M, Moldt M, et al. The RIG‐I ATPase domain structure reveals insights into ATP‐dependent antiviral signalling. EMBO Rep. 2011;12(11):1127‐1134.
    1. Takahasi K, Kumeta H, Tsuduki N, et al. Solution structures of cytosolic RNA sensor MDA5 and LGP2 C‐terminal domains: identification of the RNA recognition loop in RIG‐I‐like receptors. J Biol Chem. 2009;284(26):17465‐17474.
    1. Wu B, Peisley A, Richards C, et al. Structural basis for dsRNA recognition, filament formation, and antiviral signal activation by MDA5. Cell. 2013;152(1‐2):276‐289.
    1. Inohara Chamaillard, McDonald C, Nunez G. NOD‐LRR proteins: role in host‐microbial interactions and inflammatory disease. Annu Rev Biochem. 2005;74:355‐383.
    1. Inohara N, Nunez G. The NOD: a signaling module that regulates apoptosis and host defense against pathogens. Oncogene. 2001;20(44):6473‐6481.
    1. Agostini L, Martinon F, Burns K, McDermott MF, Hawkins PN, Tschopp J. NALP3 forms an IL‐1beta‐processing inflammasome with increased activity in Muckle‐Wells autoinflammatory disorder. Immunity. 2004;20(3):319‐325.
    1. Davis BK, Roberts RA, Huang MT, et al. Cutting edge: NLRC5‐dependent activation of the inflammasome. J Immunol. 2011;186(3):1333‐1337.
    1. Hornung V, Ablasser A, Charrel‐Dennis M, et al. AIM2 recognizes cytosolic dsDNA and forms a caspase‐1‐activating inflammasome with ASC. Nature. 2009;458(7237):514‐518.
    1. Van Gorp H, Kuchmiy A, Van Hauwermeiren F, Lamkanfi M. NOD‐like receptors interfacing the immune and reproductive systems. FEBS J. 2014;281(20):4568‐4582.
    1. Rogers NC, Slack EC, Edwards AD, et al. Syk‐dependent cytokine induction by Dectin‐1 reveals a novel pattern recognition pathway for C type lectins. Immunity. 2005;22(4):507‐517.
    1. Geijtenbeek TB, Gringhuis SI. Signalling through C‐type lectin receptors: shaping immune responses. Nat Rev Immunol. 2009;9(7):465‐479.
    1. Hara H, Tsuchiya K, Kawamura I, et al. Phosphorylation of the adaptor ASC acts as a molecular switch that controls the formation of speck‐like aggregates and inflammasome activity. Nature Immunol. 2013;14(12):1247‐1255.
    1. Strasser D, Neumann K, Bergmann H, et al. Syk kinase‐coupled C‐type lectin receptors engage protein kinase C‐sigma to elicit Card9 adaptor‐mediated innate immunity. Immunity. 2012;36(1):32‐42.
    1. Hemmi H, Takeuchi O, Kawai T, et al. A Toll‐like receptor recognizes bacterial DNA. Nature. 2000;408(6813):740‐745.
    1. Chiu YH, Macmillan JB, Chen ZJ. RNA polymerase III detects cytosolic DNA and induces type I interferons through the RIG‐I pathway. Cell. 2009;138(3):576‐591.
    1. Sun L, Wu J, Du F, Chen X, Chen ZJ. Cyclic GMP‐AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. Science (New York, NY). 2013;339(6121):786‐791.
    1. Gallego‐Marin C, Schrum JE, Andrade WA, et al. Cyclic GMP‐AMP synthase is the cytosolic sensor of plasmodium falciparum genomic DNA and activates type I IFN in malaria. J Immunol. 2018;200(2):768‐774.
    1. Jensen S, Thomsen AR. Sensing of RNA viruses: a review of innate immune receptors involved in recognizing RNA virus invasion. J Virol. 2012;86(6):2900‐2910.
    1. Ma DY, Suthar MS. Mechanisms of innate immune evasion in re‐emerging RNA viruses. Current opinion in virology. 2015;12:26‐37.
    1. Nelemans T, Kikkert M. Viral innate immune evasion and the pathogenesis of emerging RNA virus infections. Viruses. 2019;11(10):961.
    1. Ivashkiv LB, Donlin LT. Regulation of type I interferon responses. Nat Rev Immunol. 2014;14(1):36‐49.
    1. Cao L, Ji Y, Zeng L, et al. P200 family protein IFI204 negatively regulates type I interferon responses by targeting IRF7 in nucleus. PLOS Pathog. 2019;15(10):e1008079.
    1. Gordon S. Pattern recognition receptors: doubling up for the innate immune response. Cell. 2002;111(7):927‐930.
    1. Baccala R, Gonzalez‐Quintial R, Lawson BR, et al. Sensors of the innate immune system: their mode of action. Nat Rev Rheumatol. 2009;5(8):448‐456.
    1. Phadwal K, Alegre‐Abarrategui J, Watson AS, et al. A novel method for autophagy detection in primary cells: impaired levels of macroautophagy in immunosenescent T cells. Autophagy. 2012;8(4):677‐689.
    1. Seranova E, Ward C, Chipara M, Rosenstock TR, Sarkar S. In vitro screening platforms for identifying autophagy modulators in mammalian cells. Methods Mol Biol. 2019;1880:389‐428.
    1. Hou J, Wang P, Lin L, et al. MicroRNA‐146a feedback inhibits RIG‐I‐dependent Type I IFN production in macrophages by targeting TRAF6, IRAK1, and IRAK2. J Immunol. 2009;183(3):2150‐2158.
    1. Schneider WM, Chevillotte MD, Rice CM. Interferon‐stimulated genes: a complex web of host defenses. Annu Rev Immunol. 2014;32:513‐545.
    1. Spiegel M, Pichlmair A, Martinez‐Sobrido L, et al. Inhibition of beta interferon induction by severe acute respiratory syndrome coronavirus suggests a two‐step model for activation of interferon regulatory factor 3. J Virol. 2005;79(4):2079‐2086.
    1. Kopecky‐Bromberg SA, Martinez‐Sobrido L, Frieman M, Baric RA, Palese P. Severe acute respiratory syndrome coronavirus open reading frame (ORF) 3b, ORF 6, and nucleocapsid proteins function as interferon antagonists. J Virol. 2007;81(2):548‐557.
    1. Lu X, Pan J, Tao J, Guo D. SARS‐CoV nucleocapsid protein antagonizes IFN‐beta response by targeting initial step of IFN‐beta induction pathway, and its C‐terminal region is critical for the antagonism. Virus Genes. 2011;42(1):37‐45.
    1. Liu Y, Zhang Z, Zhao X, et al. Enterovirus 71 inhibits cellular type I interferon signaling by downregulating JAK1 protein expression. Viral Immunol. 2014;27(6):267‐276.
    1. Okumura A, Pitha PM, Yoshimura A, Harty RN. Interaction between Ebola virus glycoprotein and host toll‐like receptor 4 leads to induction of proinflammatory cytokines and SOCS1. J Virol. 2010;84(1):27‐33.
    1. Pauli EK, Schmolke M, Wolff T, et al. Influenza A virus inhibits type I IFN signaling via NF‐kappaB‐dependent induction of SOCS‐3 expression. PLOS Pathog. 2008;4(11):e1000196.
    1. Kaewraemruaen C, Ritprajak P, Hirankarn N. Dendritic cells as key players in systemic lupus erythematosus. Asian Pac J Allergy Immunol. 2019. 10.12932/AP-070919-0639
    1. Wu L, Dakic A. Development of dendritic cell system. Cell Mol Immunol. 2004;1(2):112‐118.
    1. Nouri‐Shirazi M, Guinet E. Exposure to nicotine adversely affects the dendritic cell system and compromises host response to vaccination. J Immunol. 2012;188(5):2359‐2370.
    1. Guo Y, Xu WW, Song J, Deng W, Liu DQ, Zhang HT. Intracellular overexpression of HIV‐1 Nef impairs differentiation and maturation of monocytic precursors towards dendritic cells. PLOS One. 2012;7(7):e40179.
    1. Tu Z, Hamalainen‐Laanaya HK, Nishitani C, Kuroki Y, Crispe IN, Orloff MS. HCV core and NS3 proteins manipulate human blood‐derived dendritic cell development and promote Th 17 differentiation. Int Immunol. 2012;24(2):97‐106.
    1. Fairman P, Angel JB. The effect of human immunodeficiency virus‐1 on monocyte‐derived dendritic cell maturation and function. Clin Exp Immunol. 2012;170(1):101‐113.
    1. Cardone M, Ikeda KN, Varano B, Gessani S, Conti L. HIV‐1‐induced impairment of dendritic cell cross talk with gammadelta T lymphocytes. J Virol. 2015;89(9):4798‐4808.
    1. White MR, Tecle T, Crouch EC, Hartshorn KL. Impact of neutrophils on antiviral activity of human bronchoalveolar lavage fluid. Am J Physiol. 2007;293(5):L1293‐L1299.
    1. Campbell O, Gagnon J, Rubin JE. Antibacterial activity of chemotherapeutic drugs against Escherichia coli and Staphylococcus pseudintermedius. Lett Appl Microbiol. 2019;69(5):353‐357.
    1. Zharkova MS, Orlov DS, Golubeva OY, et al. Application of antimicrobial peptides of the innate immune system in combination with conventional antibiotics‐A novel way to combat antibiotic resistance? Front Cell Infect Microbiol. 2019;9:128.
    1. Lehrer RI, Lichtenstein AK, Ganz T. Defensins: antimicrobial and cytotoxic peptides of mammalian cells. Annu Rev Immunol. 1993;11:105‐128.
    1. Li SZ, Shu QP, Song Y, et al. Phosphorylation of MAVS/VISA by Nemo‐like kinase (NLK) for degradation regulates the antiviral innate immune response. Nat Commun. 2019;10(1):3233.
    1. Daher KA, Selsted ME, Lehrer RI. Direct inactivation of viruses by human granulocyte defensins. J Virol. 1986;60(3):1068‐1074.
    1. Nakashima H, Yamamoto N, Masuda M, Fujii N. Defensins inhibit HIV replication in vitro. AIDS. 1993;7(8):1129.
    1. Zapata W, Aguilar‐Jiménez W, Feng Z, et al. Identification of innate immune antiretroviral factors during in vivo and in vitro exposure to HIV‐1. Microb Infect. 2016;18(3):211‐219.
    1. Yasui F, Kai C, Kitabatake M, et al. Prior immunization with severe acute respiratory syndrome (SARS)‐associated coronavirus (SARS‐CoV) nucleocapsid protein causes severe pneumonia in mice infected with SARS‐CoV. J Immunol. 2008;181(9):6337‐6348.
    1. Zhu X, Wang Y, Zhang H, et al. Genetic variation of the human alpha‐2‐Heremans‐Schmid glycoprotein (AHSG) gene associated with the risk of SARS‐CoV infection. PLOS One. 2011;6(8):e23730.
    1. Chan JF, Lau SK, To KK, Cheng VC, Woo PC, Yuen KY. Middle East respiratory syndrome coronavirus: another zoonotic betacoronavirus causing SARS‐like disease. Clin Microbiol Rev. 2015;28(2):465‐522.
    1. Cheng VC, Lau SK, Woo PC, Yuen KY. Severe acute respiratory syndrome coronavirus as an agent of emerging and reemerging infection. Clin Microbiol Rev. 2007;20(4):660‐694.
    1. Sato K, Misawa N, Takeuchi JS, et al. Experimental adaptive evolution of simian immunodeficiency virus sivcpz to pandemic human immunodeficiency virus type 1 by using a humanized mouse model. J Virol. 2018;92(4):e01905‐17.
    1. Cecere TE, Todd SM, Leroith T. Regulatory T cells in arterivirus and coronavirus infections: do they protect against disease or enhance it? Viruses. 2012;4(5):833‐846.
    1. Maloir Q, Ghysen K, von Frenckell C, Louis R, Guiot J. [Acute respiratory distress revealing antisynthetase syndrome]. Rev Med Liege. 2018;73(7‐8):370‐375.
    1. Zhao J, Li K, Wohlford‐Lenane C, et al. Rapid generation of a mouse model for Middle East respiratory syndrome. Proc Natl Acad Sci USA. 2014;111(13):4970‐4975.
    1. Pascal KE, Coleman CM, Mujica AO, et al. Pre‐ and postexposure efficacy of fully human antibodies against Spike protein in a novel humanized mouse model of MERS‐CoV infection. Proc Natl Acad Sci USA. 2015;112(28):8738‐8743.
    1. Channappanavar R, Fett C, Zhao J, Meyerholz DK, Perlman S. Virus‐specific memory CD8 T cells provide substantial protection from lethal severe acute respiratory syndrome coronavirus infection. J Virol. 2014;88(19):11034‐11044.
    1. Ng OW, Chia A, Tan AT, et al. Memory T cell responses targeting the SARS coronavirus persist up to 11 years post‐infection. Vaccine. 2016;34(17):2008‐2014.
    1. Chen J, Lau YF, Lamirande EW, et al. Cellular immune responses to severe acute respiratory syndrome coronavirus (SARS‐CoV) infection in senescent BALB/c mice: CD4+ T cells are important in control of SARS‐CoV infection. J Virol. 2010;84(3):1289‐1301.
    1. Manni ML, Robinson KM, Alcorn JF. A tale of two cytokines: IL‐17 and IL‐22 in asthma and infection. Expert review of respiratory medicine. 2014;8(1):25‐42.
    1. Bunte K, Beikler T. Th17 Cells and the IL‐23/IL‐17 axis in the pathogenesis of periodontitis and immune‐mediated inflammatory diseases. Int J Mol Sci. 2019;20(14):3394.
    1. Dutzan N, Abusleme L. T helper 17 cells as pathogenic drivers of periodontitis. Adv Exp Med Biol. 2019;1197:107‐117.
    1. Yang Y, Xiong Z, Zhang S, et al. Bcl‐xL inhibits T‐cell apoptosis induced by expression of SARS coronavirus E protein in the absence of growth factors. Biochem J. 2005;392(Pt 1):135‐143.
    1. Mubarak A, Alturaiki W, Hemida MG. Middle East respiratory syndrome coronavirus (MERS‐CoV): infection, immunological response, and vaccine development. J Immunol Res. 2019;2019:6491738‐11.
    1. Ababneh M, Alrwashdeh M, Khalifeh M. Recombinant adenoviral vaccine encoding the spike 1 subunit of the Middle East Respiratory Syndrome Coronavirus elicits strong humoral and cellular immune responses in mice. Vet World. 2019;12(10):1554‐1562.
    1. Tuhin ali M, Morshed MM, Musa MA, et al. Computer aided prediction and identification of potential epitopes in the receptor binding domain (RBD) of spike (S) glycoprotein of MERS‐CoV. Bioinformation. 2014;10(8):533‐538.
    1. Niu P, Zhang S, Zhou P, et al. Ultrapotent human neutralizing antibody repertoires against Middle East Respiratory syndrome coronavirus from a recovered patient. J Infect Dis. 2018;218(8):1249‐1260.
    1. Chen Z, Bao L, Chen C, et al. Human neutralizing monoclonal antibody inhibition of Middle East Respiratory Syndrome coronavirus replication in the common marmoset. J Infect Dis. 2017;215(12):1807‐1815.
    1. Niu P, Zhao G, Deng Y, et al. A novel human mAb (MERS‐GD27) provides prophylactic and postexposure efficacy in MERS‐CoV susceptible mice. Science China Life sciences. 2018;61(10):1280‐1282.
    1. Baker S, Kessler E, Darville‐Bowleg L, Merchant M. Different mechanisms of serum complement activation in the plasma of common (Chelydra serpentina) and alligator (Macrochelys temminckii) snapping turtles. PLOS One. 2019;14(6):e0217626.
    1. Sun S, Zhao G, Liu C, et al. Inhibition of complement activation alleviates acute lung injury induced by highly pathogenic avian influenza H5N1 virus infection. Am J Respir Cell Mol Biol. 2013;49(2):221‐230.
    1. Gralinski LE, Sheahan TP, Morrison TE, et al. Complement activation contributes to severe acute respiratory syndrome coronavirus pathogenesis. mBio. 2018;9(5):e01753‐18.
    1. Ying T, Du L, Ju TW, et al. Exceptionally potent neutralization of Middle East respiratory syndrome coronavirus by human monoclonal antibodies. J Virol. 2014;88(14):7796‐7805.
    1. Houser KV, Gretebeck L, Ying T, et al. Prophylaxis with a Middle East Respiratory Syndrome Coronavirus (MERS‐CoV)‐specific human monoclonal antibody protects rabbits from MERS‐CoV Infection. J Infect Dis. 2016;213(10):1557‐1561.
    1. van Doremalen N, Falzarano D, Ying T, et al. Efficacy of antibody‐based therapies against Middle East respiratory syndrome coronavirus (MERS‐CoV) in common marmosets. Antiviral Res. 2017;143:30‐37.
    1. Coleman CM, Liu YV, Mu H, et al. Purified coronavirus spike protein nanoparticles induce coronavirus neutralizing antibodies in mice. Vaccine. 2014;32(26):3169‐3174.
    1. Weingartl H, Czub M, Czub S, et al. Immunization with modified vaccinia virus Ankara‐based recombinant vaccine against severe acute respiratory syndrome is associated with enhanced hepatitis in ferrets. J Virol. 2004;78(22):12672‐12676.
    1. Chen W. Antibody response and viraemia during the course of severe acute respiratory syndrome (SARS)‐associated coronavirus infection. J Med Microbiol. 2004;53(Pt 5):435‐438.

Source: PubMed

Patrocinadores e Colaboradores

Condições médicas

Intervenções de drogas

3
Se inscrever