Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology

Seminars in Immunopathology, Год журнала: 2017, Номер 39(5), С. 529 - 539

Опубликована: Май 2, 2017

Human coronaviruses (hCoVs) can be divided into low pathogenic and highly coronaviruses. The CoVs infect the upper respiratory tract cause mild, cold-like illness. In contrast, hCoVs such as severe acute syndrome CoV (SARS-CoV) Middle East (MERS-CoV) predominantly lower airways fatal pneumonia. Severe pneumonia caused by is often associated with rapid virus replication, massive inflammatory cell infiltration elevated pro-inflammatory cytokine/chemokine responses resulting in lung injury (ALI), distress (ARDS). Recent studies experimentally infected animal strongly suggest a crucial role for virus-induced immunopathological events causing after hCoV infections. Here we review current understanding of how dysregulated immune response may immunopathology leading to deleterious clinical manifestations

Язык: Английский

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Immune responses in COVID-19 and potential vaccines: Lessons learned from SARS and MERS epidemic

Asian Pacific Journal of Allergy and Immunology, Год журнала: 2020, Номер unknown

Опубликована: Янв. 1, 2020

As the world is witnessing epidemic of COVID-19, a disease caused by novel coronavirus, SARS-CoV-2, emerging genetics and clinical evidences suggest similar path to those SARS MERS.The rapid genomic sequencing open access data, together with advanced vaccine technology, are expected give us more knowledge on pathogen itself, including host immune response as well plan for therapeutic vaccines in near future.This review aims provide comparative view among SARS-CoV, MERS-CoV newly hope gain better understanding host-pathogen interaction, responses, evasion strategies.This predictive may help designing an intervention or preventive COVID-19 future.

Язык: Английский

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Mechanisms of SARS-CoV-2 Transmission and Pathogenesis

Trends in Immunology, Год журнала: 2020, Номер 41(12), С. 1100 - 1115

Опубликована: Окт. 14, 2020

The emergence of SARS-CoV-2 from China and the rapidity a worldwide pandemic has promoted global collaboration, built on body work established previous SARS-CoV MERS-CoV outbreaks. These past experiences have aided swiftness by which research community responded with an astonishing work.SARS-CoV-2 is novel virus in Betacoronavirus genus exhibits similarities to genome structure, tissue tropism, viral pathogenesis. Yet, appears be more transmissible diversity immune responses are poorly understood.Highly pathogenic coronaviruses display potent interferon (IFN) antagonism, evident cases severe COVID-19 reduced IFN signaling, overaggressive response compounded heightened cytokines/chemokines.Animal models for recapitulate important aspects human that essential evaluating current prospective antiviral therapeutics vaccine candidates. acute respiratory syndrome coronavirus 2 (SARS-CoV-2) marks third highly spill over into population. broad tropism likely perpetuating pandemic. However, questions remain regarding its transmissibility In this review, we summarize research, emphasis transmission, pathogenesis, antagonism. We further present advances animal understanding pathogenesis SARS-CoV-2, development, therapeutic testing. When necessary, comparisons made studies SARS provide perspectives infectious disease 2019 (COVID-19), as well draw inferences future investigations. CoVs caused three large-scale outbreaks two decades: (SARS), Middle Eastern (MERS), now COVID-19. origin was traced back cluster pneumonia connected wet seafood market Wuhan City, Hubei Province, [1.Zhou P. et al.A outbreak associated new probable bat origin.Nature. 2020; 579: 270-273Crossref PubMed Scopus (3510) Google Scholar]. Following spillover zoonotic (see Glossary), confirmed etiological agent related Scholar,2.Peiris J. al.Coronavirus possible cause syndrome.Lancet. 2003; 361: 1319-1325Abstract Full Text PDF (1895) first patients developed symptoms December 1, after rapid human-to-human transmission intercontinental spread later ensued, being declared WHO March 2020 [3.Huang C. al.Clinical features infected Wuhan, China.Lancet. 395: 497-506Abstract (8744) Since then, ~35 million people been >1 deaths 235 countries, areas, or territories [4.WHO Coronavirus Disease (COVID-19) Pandemic. WHO, 2020Google Although less lethal than MERS-CoV, higher. To find solutions contain raging pandemic, efforts quickly mobilized, each day resulting basic clinical therapy, diagnosis, drug epidemiology. Here, conduct comprehensive review state principal focus mechanisms stemming studies. family Coronaviridae enveloped, positive-sense single-stranded RNA viruses [5.Gorbalenya A.E. al.The species Severe syndrome-related coronavirus: classifying 2019-nCoV naming it SARS-CoV-2.Nat. Microbiol. 5: 536-544Crossref (1033) All CoVs, including belong genus, group sequence shares ~80% identity ~50% Scholar,6.Lu R. al.Genomic characterisation epidemiology implications origins receptor binding.Lancet. 565-574Abstract (2388) Its comprises 14 open reading frames (ORFs), two-thirds encode 16 nonstructural proteins (nsp 1–16) make up replicase complex [6.Lu Scholar,7.Zhang Y.Z. Holmes E.C. A genomic perspective SARS-CoV-2.Cell. 181: 223-227Abstract (126) remaining one-third encodes nine accessory (ORF) four structural proteins: spike (S), envelope (E), membrane (M), nucleocapsid (N), Spike mediates entry host cells [8.Perlman S. Netland Coronaviruses post-SARS: update replication pathogenesis.Nat. Rev. 2009; 7: 439-450Crossref (548) S gene variable SARS-CoV, sharing <75% nucleotide Scholar,9.Wu F. China.Nature. 265-269Crossref (1535) receptor-binding domain (RBD) direct contact cellular receptor, angiotensin-converting enzyme (ACE2), S1/S2 polybasic cleavage site proteolytically cleaved cathepsin L transmembrane protease serine (TMPRSS2) (Figure 1) Scholar,10.Hoffmann M. al.SARS-CoV-2 cell depends ACE2 TMPRSS2 blocked clinically proven inhibitor.Cell. 271-280Abstract (2529) facilitates at plasma surface, whereas activates endosomes can compensate lack [10.Hoffmann Once released cytosol, ORF1a ORF1b translated proteins, individual nsps (via proteases: PLpro); these form RNA-dependent polymerase (nsp12 derived ORF1b) components rearrange endoplasmic reticulum (ER) double-membrane vesicles (DMVs) facilitate subgenomic RNAs (sgRNA); latter particle formation [11.Snijder E.J. al.Ultrastructure complex.J. Virol. 2006; 80: 5927-5940Crossref (234) Scholar,12.Wu H.-Y. Brian D.A. Subgenomic messenger amplification coronaviruses.Proc. Natl. Acad. Sci. U. A. 2010; 107: 12257-12262Crossref (0) establishment susceptibility permissiveness specific cell. During epidemic, often presented respiratory-like illnesses progressed pneumonia, observations mirroring course COVID-19, suggesting lung primary [13.Peiris progression load coronavirus-associated pneumonia: study.Lancet. 1767-1772Abstract (1356) Both were then found bind same Scholar,14.Wrapp D. al.Cryo-EM structure prefusion conformation.Science. 367: 1260-1263Crossref (4) Scholar,15.Li W. al.Angiotensin-converting functional coronavirus.Nature. 426: 450-454Crossref (2042) Of note, key mutations RBD additional close contacts ACE2, correlating higher binding affinity perhaps increased infectivity Scholar,16.Yan al.Structural basis recognition full-length ACE2.Science. 1444-1448Crossref (720) presence unique furin junction also suspected enhance events, although remains investigated [17.Shang al.Cell SARS-CoV-2.Proc. 117: 11727-11734Crossref (160) Scholar,18.Hoffmann multibasic protein infection cells.Mol. Cell. 78: 779-784Abstract (140) currently predominant isolate carries D614G mutation absent presumptive common ancestor, infectious, underlying, part, efficiency [19.Yurkovetskiy L. analysis variant.Cell. (Published online September 15, 2020. https://doi.org/10.1016/j.cell.2020.09.032)Abstract (1) Scholar, 20.Li Q. impact antigenicity.Cell. 182: 1284-1294Abstract (23) 21.Korber B. al.Tracking changes Spike: evidence increases virus.Cell. 812-827Abstract (149) upper tract (URT) variant does not correlate severity, linked just [21.Korber SARS-CoVs enter via tract, airway alveolar epithelial cells, vascular endothelial macrophages among their targets [22.Jia H.P. al.ACE2 expression depend differentiation epithelia.J. 2005; 79: 14614-14621Crossref (232) 23.Hamming I. al.Tissue distribution protein, coronavirus. step pathogenesis.J. Pathol. 2004; 203: 631-637Crossref (1316) 24.Kuba K. crucial role angiotensin converting (ACE2) coronavirus-induced injury.Nat. Med. 11: 875-879Crossref (1069) probably 'ground-zero' early subsequent due [25.Ziegler C.G.K. interferon-stimulated detected subsets across tissues.Cell. 1016-1035Abstract (278) mRNA many mammalian (bat, ferret, cat, dog, etc.) biopsies, rather low compared extrapulmonary tissues [26.Sun al.Atlas mammals reveals insights SARS-CoV-2.BioRxiv. 31, https://doi.org/10.1101/2020.03.30.015644)Google Thus, may additional, unappreciated cell-intrinsic factors aid efficient infection. First, heavily TMPRSS2, because nearly undetectable amounts still support long [27.Shulla entry.J. 2011; 85: 873-882Crossref (183) Second, genes, such endosomal sorting required transport (ESCRT) machinery members (including CHMP3, CHMP5, CHMP1A, VPS37B) pro-SARS-CoV-2 lifecycle small population type II abundant relative ACE2-deficient [28.Zhao Y. al.Single-cell profiling SARS-CoV-2.Am. Respir. Crit. Care 202: 756-759Crossref (29) This suggests hijacks high other proviral genes productive replication. Third, lung, main SARS-CoVs, contingent regulation transcriptional levels [24.Kuba Scholar,25.Ziegler Scholar,29.Imai protects failure.Nature. 436: 112-116Crossref (979) 30.Wang al.Endocytosis together ACE2.Virus Res. 2008; 136: 8-15Crossref 31.Smith J.C. al.Cigarette smoke exposure inflammatory signaling increase tract.Dev. 53: 514-529Abstract (41) For example, upregulated I interferons (IFNs) Scholar,31.Smith Scholar] during Lastly, contains insertion RRAR precleaved furin, thus reducing dependence target proteases (TMPRSS2/cathepsin L) potentially extending given active abundantly expressed bronchial [32.Follis K.E. al.Furin glycoprotein enhances cell-cell fusion but affect virion entry.Virology. 350: 358-369Crossref (69) Scholar,33.Lukassen primarily transient secretory cells.EMBO 39e105114Crossref (144) One distinctions between ability efficiently infect URT, nasopharyngeal (NP) and/or oropharyngeal (OP) tissues, possibly nasal oral [23.Hamming Scholar,34.Hui K.P.Y. al.Tropism, competence, innate conjunctiva: ex-vivo in-vitro cultures.Lancet 8: 687-695Abstract (48) 35.COVID-19 Investigation Team Clinical virologic characteristics 12 United States.Nat. 26: 861-868Crossref 36.Xu H. al.High mucosa.Int. Oral 12: 8Crossref (481) readily detectable titers URT mucus prodromal periods might help explain effective [37.Wölfel al.Virological assessment hospitalized COVID-2019.Nature. 581: 465-469Crossref (978) Human enteric infections, degrees pathogenicity [38.Su al.Epidemiology, genetic recombination, coronaviruses.Trends 2016; 24: 490-502Abstract (621) Indeed, within intestinal tracts, specifically brush border enterocytes Scholar,26.Sun Scholar,39.Zhang digestive system potential route 2019-nCov infection: bioinformatics based single-cell transcriptomes.Gut. 69: 1010-1018Crossref Accordingly, gastrointestinal illness frequently reported [40.Cholankeril G. prevalence concurrent manifestations SARS-CoV-2: experience California.Gastroenterology. 159: 775-777Abstract (67) Scholar,41.Xiao al.Evidence SARS-CoV-2.Gastroenterology. 158: 1831-1833Abstract (550) Scholar], consistent recovery stool samples [42.Leung W.K. al.Enteric involvement syndrome-associated infection.Gastroenterology. 125: 1011-1017Abstract (280) fecal–oral CoVs. ~20% examined had feces, even subsided, prolonged [41.Xiao testing warranted, data suggest possibility occurs. Evidently, robust epidemiological needed conclusively demonstrate whether recovering able SARS-CoV-2. transmitted through droplets, aerosol, contaminated surfaces, epidemic [43.Yu I.T.S. airborne virus.N. Engl. 1731-1739Crossref (567) 44.Otter J.A. al.Transmission MERS influenza healthcare settings: dry surface contamination.J. Hosp. Infect. 92: 235-250Abstract (175) 45.Li al.Role air largest nosocomial Hong Kong.Int. Indoor Environ. Health. 15: 83-95Google Early reports cough, ground glass opacities, symptom suggested communicability 2) 2.Peiris 3.Huang Direct droplets reinforced both lower (LRT), increasing number indicating exhibiting coughing [35.COVID-19 Scholar,46.Wang 138 coronavirus-infected China.JAMA. 323: 1061-1069Crossref (5105) 47.Li al.Early dynamics China, pneumonia.N. 382: 1199-1207Crossref (3264) 48.Chan J.F.W. familial person-to-person transmission: study cluster.Lancet. 514-523Abstract (2169) So far, reproduction (R0) ~2.2, case tracking beginning doubling time 5 days [47.Li Scholar,49.Ferrett al.Quantifying control digital tracing.Science. 368eabb6936Crossref (219) Furthermore, there nonsymptomatic/presymptomatic contrast [50.Arons M.M. al.Presymptomatic infections skilled nursing facility.N. 2081-2090Crossref (336) finding underscores colonize replicate throat Scholar,51.Zou specimens patients.N. 1177-1179Crossref (1242) Scholar,52.Pan al.Viral samples.Lancet Dis. 20: 411-412Abstract (307) Based apparent disparities one modeled presymptomatic individuals, indicated R0 approached threshold sustaining own (R0 >1); contrast, corresponding estimates approximately zero [49.Ferrett Similarly, asymptomatic documented throughout [48.Chan

Язык: Английский

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Activation and evasion of type I interferon responses by SARS-CoV-2

Nature Communications, Год журнала: 2020, Номер 11(1)

Опубликована: Июль 30, 2020

The pandemic of COVID-19 has posed an unprecedented threat to global public health. However, the interplay between viral pathogen COVID-19, SARS-CoV-2, and host innate immunity is poorly understood. Here we show that SARS-CoV-2 induces overt but delayed type-I interferon (IFN) responses. By screening 23 proteins, find NSP1, NSP3, NSP12, NSP13, NSP14, ORF3, ORF6 M protein inhibit Sendai virus-induced IFN-β promoter activation, whereas NSP2 S exert opposite effects. Further analyses suggest inhibits both type I IFN production downstream signaling, C-terminus region critical for its antagonistic effect. Finally, treatment effectively blocks replication. In summary, our study shows perturbs immune response via structural nonstructural thus provides insights into pathogenesis SARS-CoV-2.

Язык: Английский

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Evasion of Type I Interferon by SARS-CoV-2

Cell Reports, Год журнала: 2020, Номер 33(1), С. 108234 - 108234

Опубликована: Сен. 19, 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication and host immune response determine disease 2019 (COVID-19), but studies evaluating viral evasion of are lacking. Here, we use unbiased screening to identify SARS-CoV-2 proteins that antagonize type I interferon (IFN-I) response. We found three IFN-I production via distinct mechanisms: nonstructural protein 6 (nsp6) binds TANK binding kinase 1 (TBK1) suppress regulatory factor 3 (IRF3) phosphorylation, nsp13 blocks TBK1 open reading frame (ORF6) importin Karyopherin α (KPNA2) inhibit IRF3 nuclear translocation. two sets signaling through blocking signal transducer activator transcription (STAT1)/STAT2 phosphorylation or Remarkably, nsp1 nsp6 more efficiently than SARS-CoV Middle East (MERS-CoV). Thus, when treated with IFN-I, a replicon replicates higher level chimeric replicons containing from MERS-CoV. Altogether, the study provides insights on its potential impact transmission pathogenesis.

Язык: Английский

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COVID-19: Immunology and treatment options

Clinical Immunology, Год журнала: 2020, Номер 215, С. 108448 - 108448

Опубликована: Апрель 27, 2020

Язык: Английский

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COVID-19: Pathogenesis, cytokine storm and therapeutic potential of interferons

Cytokine & Growth Factor Reviews, Год журнала: 2020, Номер 53, С. 66 - 70

Опубликована: Май 7, 2020

Язык: Английский

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Innate Immune Evasion by Human Respiratory RNA Viruses

Journal of Innate Immunity, Год журнала: 2019, Номер 12(1), С. 4 - 20

Опубликована: Окт. 14, 2019

The impact of respiratory virus infections on the health children and adults can be very significant. Yet, in contrast to most other childhood as well viral bacterial diseases, prophylactic vaccines or effective antiviral treatments against are either still not available, provide only limited protection. Given widespread prevalence, a general lack natural sterilizing immunity, and/or high morbidity lethality rates diseases caused by influenza, syncytial virus, coronaviruses, rhinoviruses, this difficult situation is genuine societal challenge. A thorough understanding virus-host interactions during these will probably pivotal ultimately meet challenges. This review attempts comparative overview knowledge about an important part interaction between viruses their host: arms race host innate immunity immune evasion. Many, if all, viruses, including listed above, suppress responses gain window opportunity for efficient replication setting-up infection. consequences host’s response that it often incomplete, delayed diminished, displays overly strong induction (after delay) may cause tissue damage. affected also impacts subsequent adaptive responses, therefore evasion undermines fully protective immunity. In review, relevant with RNA genome briefly summarized, based shielding species away from cellular sensors discussed different angles. Subsequently, enzymatic activities discussed, causing shut-off manipulation stress granule formation. Furthermore, protease-mediated ubiquitin system addressed. Finally, perspectives use reviewed development novel strategies sketched.

Язык: Английский

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Coronavirus nonstructural protein 15 mediates evasion of dsRNA sensors and limits apoptosis in macrophages

Proceedings of the National Academy of Sciences, Год журнала: 2017, Номер 114(21)

Опубликована: Май 8, 2017

Significance Macrophages are immune cells equipped with multiple double-stranded RNA (dsRNA) sensors designed to detect viral infection and amplify innate antiviral immunity. However, many coronaviruses can infect propagate in macrophages without activating dsRNA sensors. Here we present a function of murine coronavirus nonstructural protein 15 preventing detection by host We show that expressing mutant form allow for activation sensors, resulting an early induction interferon, rapid apoptosis macrophages, protective response mice. Identifying the strategies used viruses evade provides us new approaches generating vaccines elicit robust responses

Язык: Английский

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Clinical, molecular, and epidemiological characterization of the SARS-CoV-2 virus and the Coronavirus Disease 2019 (COVID-19), a comprehensive literature review

Diagnostic Microbiology and Infectious Disease, Год журнала: 2020, Номер 98(1), С. 115094 - 115094

Опубликована: Май 30, 2020

Язык: Английский

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