1932

Abstract

Over the last two decades the world has witnessed the global spread of two genetically related highly pathogenic coronaviruses, severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2. However, the impact of these outbreaks differed significantly with respect to the hospitalizations and fatalities seen worldwide. While many studies have been performed recently on SARS-CoV-2, a comparative pathogenesis analysis with SARS-CoV may further provide critical insights into the mechanisms of disease that drive coronavirus-induced respiratory disease. In this review, we comprehensively describe clinical and experimental observations related to transmission and pathogenesis of SARS-CoV-2 in comparison with SARS-CoV, focusing on human, animal, and in vitro studies. By deciphering the similarities and disparities of SARS-CoV and SARS-CoV-2, in terms of transmission and pathogenesis mechanisms, we offer insights into the divergent characteristics of these two viruses. This information may also be relevant to assessing potential novel introductions of genetically related highly pathogenic coronaviruses.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-pathol-052620-121224
2024-01-24
2024-04-17
Loading full text...

Full text loading...

/deliver/fulltext/pathol/19/1/annurev-pathol-052620-121224.html?itemId=/content/journals/10.1146/annurev-pathol-052620-121224&mimeType=html&fmt=ahah

Literature Cited

  1. 1.
    World Health Organ 2015. Summary of probable SARS cases with onset of illness from 1 November 2002 to 31 July 2003. World Health Organization https://www.who.int/publications/m/item/summary-of-probable-sars-cases-with-onset-of-illness-from-1-november-2002-to-31-july-2003
    [Google Scholar]
  2. 2.
    de Wit E, van Doremalen N, Falzarano D, Munster VJ. 2016. SARS and MERS: recent insights into emerging coronaviruses. Nat. Rev. Microbiol. 14:52334
    [Google Scholar]
  3. 3.
    Cui J, Li F, Shi ZL. 2019. Origin and evolution of pathogenic coronaviruses. Nat. Rev. Microbiol. 17:18192
    [Google Scholar]
  4. 4.
    Cheng VC, Lau SK, Woo PC, Yuen KY. 2007. Severe acute respiratory syndrome coronavirus as an agent of emerging and reemerging infection. Clin. Microbiol. Rev. 20:66094
    [Google Scholar]
  5. 5.
    Zhu N, Zhang D, Wang W, Li X, Yang B et al. 2020. A novel coronavirus from patients with pneumonia in China, 2019. N. Engl. J. Med. 382:72733
    [Google Scholar]
  6. 6.
    Lamers MM, Haagmans BL. 2022. SARS-CoV-2 pathogenesis. Nat. Rev. Microbiol. 20:27084
    [Google Scholar]
  7. 7.
    Alwine JC, Casadevall A, Enquist LW, Goodrum FD, Imperiale MJ. 2023. A critical analysis of the evidence for the SARS-CoV-2 origin hypotheses. mBio 14:e0058323
    [Google Scholar]
  8. 8.
    Pekar JE, Magee A, Parker E, Moshiri N, Izhikevich K et al. 2022. The molecular epidemiology of multiple zoonotic origins of SARS-CoV-2. Science 377:96066
    [Google Scholar]
  9. 9.
    Worobey M, Levy JI, Malpica Serrano L, Crits-Christoph A, Pekar JE et al. 2022. The Huanan Seafood Wholesale Market in Wuhan was the early epicenter of the COVID-19 pandemic. Science 377:95159
    [Google Scholar]
  10. 10.
    Jackson CB, Farzan M, Chen B, Choe H. 2022. Mechanisms of SARS-CoV-2 entry into cells. Nat. Rev. Mol. Cell Biol. 23:320
    [Google Scholar]
  11. 11.
    Du L, He Y, Zhou Y, Liu S, Zheng BJ, Jiang S. 2009. The spike protein of SARS-CoV—a target for vaccine and therapeutic development. Nat. Rev. Microbiol. 7:22636
    [Google Scholar]
  12. 12.
    Pinto AL, Rai RK, Brown JC, Griffin P, Edgar JR et al. 2022. Ultrastructural insight into SARS-CoV-2 entry and budding in human airway epithelium. Nat. Commun. 13:1609
    [Google Scholar]
  13. 13.
    Wu CT, Lidsky PV, Xiao Y, Cheng R, Lee IT et al. 2023. SARS-CoV-2 replication in airway epithelia requires motile cilia and microvillar reprogramming. Cell 186:11230.e20
    [Google Scholar]
  14. 14.
    Sims AC, Baric RS, Yount B, Burkett SE, Collins PL, Pickles RJ. 2005. Severe acute respiratory syndrome coronavirus infection of human ciliated airway epithelia: role of ciliated cells in viral spread in the conducting airways of the lungs. J. Virol. 79:1551124
    [Google Scholar]
  15. 15.
    Sims AC, Burkett SE, Yount B, Pickles RJ. 2008. SARS-CoV replication and pathogenesis in an in vitro model of the human conducting airway epithelium. Virus Res. 133:3344
    [Google Scholar]
  16. 16.
    Gu J, Korteweg C. 2007. Pathology and pathogenesis of severe acute respiratory syndrome. Am. J. Pathol. 170:113647
    [Google Scholar]
  17. 17.
    Huang C, Wang Y, Li X, Ren L, Zhao J et al. 2020. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 395:497506
    [Google Scholar]
  18. 18.
    Rajgor DD, Lee MH, Archuleta S, Bagdasarian N, Quek SC. 2020. The many estimates of the COVID-19 case fatality rate. Lancet Infect. Dis. 20:77677
    [Google Scholar]
  19. 19.
    Huang L, Zhang X, Zhang X, Wei Z, Zhang L et al. 2020. Rapid asymptomatic transmission of COVID-19 during the incubation period demonstrating strong infectivity in a cluster of youngsters aged 16–23 years outside Wuhan and characteristics of young patients with COVID-19: a prospective contact-tracing study. J. Infect. 80:e113
    [Google Scholar]
  20. 20.
    Nicholls JM, Poon LL, Lee KC, Ng WF, Lai ST et al. 2003. Lung pathology of fatal severe acute respiratory syndrome. Lancet 361:177378
    [Google Scholar]
  21. 21.
    Gu J, Gong E, Zhang B, Zheng J, Gao Z et al. 2005. Multiple organ infection and the pathogenesis of SARS. J. Exp. Med. 202:41524
    [Google Scholar]
  22. 22.
    Bradley BT, Maioli H, Johnston R, Chaudhry I, Fink SL et al. 2020. Histopathology and ultrastructural findings of fatal COVID-19 infections in Washington State: a case series. Lancet 396:32032
    [Google Scholar]
  23. 23.
    Schurink B, Roos E, Radonic T, Barbe E, Bouman CSC et al. 2020. Viral presence and immunopathology in patients with lethal COVID-19: a prospective autopsy cohort study. Lancet Microbe 1:e29099
    [Google Scholar]
  24. 24.
    Roberts A, Vogel L, Guarner J, Hayes N, Murphy B et al. 2005. Severe acute respiratory syndrome coronavirus infection of golden Syrian hamsters. J. Virol. 79:50311
    [Google Scholar]
  25. 25.
    Roberts A, Subbarao K. 2006. Animal models for SARS. Adv. Exp. Med. Biol. 581:46371
    [Google Scholar]
  26. 26.
    Roberts A, Lamirande EW, Vogel L, Jackson JP, Paddock CD et al. 2008. Animal models and vaccines for SARS-CoV infection. Virus Res 133:2032
    [Google Scholar]
  27. 27.
    Chu H, Chan JF, Yuen KY. 2022. Animal models in SARS-CoV-2 research. Nat. Methods 19:39294
    [Google Scholar]
  28. 28.
    Rizvi ZA, Dalal R, Sadhu S, Binayke A, Dandotiya J et al. 2022. Golden Syrian hamster as a model to study cardiovascular complications associated with SARS-CoV-2 infection. eLife 11:e73522
    [Google Scholar]
  29. 29.
    Muñoz-Fontela C, Dowling WE, Funnell SGP, Gsell PS, Riveros-Balta AX et al. 2020. Animal models for COVID-19. Nature 586:50915
    [Google Scholar]
  30. 30.
    Tiwari S, Goel G, Kumar A. 2022. Natural and genetically-modified animal models to investigate pulmonary and extrapulmonary manifestations of COVID-19. Int. Rev. Immunol. https://doi.org/10.1080/08830185.2022.2089666
    [Crossref] [Google Scholar]
  31. 31.
    Dillard JA, Martinez SA, Dearing JJ, Montgomery SA, Baxter VK. 2023. Animal models for the study of SARS-CoV-2-induced respiratory disease and pathology. Comp. Med. 73:7290
    [Google Scholar]
  32. 32.
    Trimpert J, Vladimirova D, Dietert K, Abdelgawad A, Kunec D et al. 2020. The Roborovski dwarf hamster is a highly susceptible model for a rapid and fatal course of SARS-CoV-2 infection. Cell Rep. 33:108488
    [Google Scholar]
  33. 33.
    Lawler JV, Endy TP, Hensley LE, Garrison A, Fritz EA et al. 2006. Cynomolgus macaque as an animal model for severe acute respiratory syndrome. PLOS Med. 3:e149
    [Google Scholar]
  34. 34.
    Qin C, Wang J, Wei Q, She M, Marasco WA et al. 2005. An animal model of SARS produced by infection of Macaca mulatta with SARS coronavirus. J. Pathol. 206:25159
    [Google Scholar]
  35. 35.
    van den Brand JM, Haagmans BL, van Riel D, Osterhaus AD, Kuiken T. 2014. The pathology and pathogenesis of experimental severe acute respiratory syndrome and influenza in animal models. J. Comp. Pathol. 151:83112
    [Google Scholar]
  36. 36.
    Blair RV, Vaccari M, Doyle-Meyers LA, Roy CJ, Russell-Lodrigue K et al. 2021. Acute respiratory distress in aged, SARS-CoV-2-infected African green monkeys but not rhesus macaques. Am. J. Pathol. 191:27482
    [Google Scholar]
  37. 37.
    Rockx B, Kuiken T, Herfst S, Bestebroer T, Lamers MM et al. 2020. Comparative pathogenesis of COVID-19, MERS, and SARS in a nonhuman primate model. Science 368:101215
    [Google Scholar]
  38. 38.
    Martina BE, Haagmans BL, Kuiken T, Fouchier RA, Rimmelzwaan GF et al. 2003. Virology: SARS virus infection of cats and ferrets. Nature 425:915
    [Google Scholar]
  39. 39.
    Blanco-Melo D, Nilsson-Payant BE, Liu WC, Uhl S, Hoagland D et al. 2020. Imbalanced host response to SARS-CoV-2 drives development of COVID-19. Cell 181:103645.e9
    [Google Scholar]
  40. 40.
    Pandey K, Acharya A, Mohan M, Ng CL, Reid SP, Byrareddy SN. 2021. Animal models for SARS-CoV-2 research: a comprehensive literature review. Transbound. Emerg. Dis. 68:186885
    [Google Scholar]
  41. 41.
    Lakdawala SS, Menachery VD. 2020. The search for a COVID-19 animal model. Science 368:94243
    [Google Scholar]
  42. 42.
    Peiris JS, Chu CM, Cheng VC, Chan KS, Hung IF et al. 2003. Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study. Lancet 361:176772
    [Google Scholar]
  43. 43.
    Cheng PK, Wong DA, Tong LK, Ip SM, Lo AC et al. 2004. Viral shedding patterns of coronavirus in patients with probable severe acute respiratory syndrome. Lancet 363:1699700
    [Google Scholar]
  44. 44.
    Zou L, Ruan F, Huang M, Liang L, Huang H et al. 2020. SARS-CoV-2 viral load in upper respiratory specimens of infected patients. N. Engl. J. Med. 382:117779
    [Google Scholar]
  45. 45.
    Zhou J, Singanayagam A, Goonawardane N, Moshe M, Sweeney FP et al. 2023. Viral emissions into the air and environment after SARS-CoV-2 human challenge: a phase 1, open label, first-in-human study. Lancet Microbe 4:8e57990
    [Google Scholar]
  46. 46.
    Khan M, Yoo SJ, Clijsters M, Backaert W, Vanstapel A et al. 2021. Visualizing in deceased COVID-19 patients how SARS-CoV-2 attacks the respiratory and olfactory mucosae but spares the olfactory bulb. Cell 184:593249.e15
    [Google Scholar]
  47. 47.
    van Doremalen N, Bushmaker T, Morris DH, Holbrook MG, Gamble A et al. 2020. Aerosol and surface stability of SARS-CoV-2 as compared with SARS-CoV-1. N. Engl. J. Med. 382:156467
    [Google Scholar]
  48. 48.
    Hwang C. 2006. Olfactory neuropathy in severe acute respiratory syndrome: report of a case. Acta Neurol. Taiwanica 15:2628
    [Google Scholar]
  49. 49.
    Richard M, Kok A, de Meulder D, Bestebroer TM, Lamers MM et al. 2020. SARS-CoV-2 is transmitted via contact and via the air between ferrets. Nat. Commun. 11:3496
    [Google Scholar]
  50. 50.
    Kutter JS, de Meulder D, Bestebroer TM, Lexmond P, Mulders A et al. 2021. SARS-CoV and SARS-CoV-2 are transmitted through the air between ferrets over more than one meter distance. Nat. Commun. 12:1653
    [Google Scholar]
  51. 51.
    Kim YI, Yu KM, Koh JY, Kim EH, Kim SM et al. 2022. Age-dependent pathogenic characteristics of SARS-CoV-2 infection in ferrets. Nat. Commun. 13:21
    [Google Scholar]
  52. 52.
    Peacock TP, Goldhill DH, Zhou J, Baillon L, Frise R et al. 2021. The furin cleavage site in the SARS-CoV-2 spike protein is required for transmission in ferrets. Nat. Microbiol. 6:899909
    [Google Scholar]
  53. 53.
    Chan JF, Zhang AJ, Yuan S, Poon VK, Chan CC et al. 2020. Simulation of the clinical and pathological manifestations of coronavirus disease 2019 (COVID-19) in a golden Syrian hamster model: implications for disease pathogenesis and transmissibility. Clin. Infect. Dis. 71:242846
    [Google Scholar]
  54. 54.
    Port JR, Yinda CK, Owusu IO, Holbrook M, Fischer R et al. 2021. SARS-CoV-2 disease severity and transmission efficiency is increased for airborne compared to fomite exposure in Syrian hamsters. Nat. Commun. 12:4985
    [Google Scholar]
  55. 55.
    Rockx B, Feldmann F, Brining D, Gardner D, LaCasse R et al. 2011. Comparative pathogenesis of three human and zoonotic SARS-CoV strains in cynomolgus macaques. PLOS ONE 6:e18558
    [Google Scholar]
  56. 56.
    Perlman S, Dandekar AA. 2005. Immunopathogenesis of coronavirus infections: implications for SARS. Nat. Rev. Immunol. 5:91727
    [Google Scholar]
  57. 57.
    Cameron MJ, Ran L, Xu L, Danesh A, Bermejo-Martin JF et al. 2007. Interferon-mediated immunopathological events are associated with atypical innate and adaptive immune responses in patients with severe acute respiratory syndrome. J. Virol. 81:8692706
    [Google Scholar]
  58. 58.
    Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ. 2020. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 395:103334
    [Google Scholar]
  59. 59.
    Planer JD, Morrisey EE. 2023. After the storm: regeneration, repair, and reestablishment of homeostasis between the alveolar epithelium and innate immune system following viral lung injury. Annu. Rev. Pathol. Mech. Dis. 18:33759
    [Google Scholar]
  60. 60.
    Nicholls JM, Butany J, Poon LL, Chan KH, Beh SL et al. 2006. Time course and cellular localization of SARS-CoV nucleoprotein and RNA in lungs from fatal cases of SARS. PLOS Med. 3:e27
    [Google Scholar]
  61. 61.
    Melms JC, Biermann J, Huang H, Wang Y, Nair A et al. 2021. A molecular single-cell lung atlas of lethal COVID-19. Nature 595:11419
    [Google Scholar]
  62. 62.
    Wang S, Yao X, Ma S, Ping Y, Fan Y et al. 2021. A single-cell transcriptomic landscape of the lungs of patients with COVID-19. Nat. Cell Biol. 23:131428
    [Google Scholar]
  63. 63.
    Chen Y, Chan VS-F, Zheng B, Chan KY-K, Xu X et al. 2007. A novel subset of putative stem/progenitor CD34+Oct-4+ cells is the major target for SARS coronavirus in human lung. J. Exp. Med. 204:252936
    [Google Scholar]
  64. 64.
    He L, Ding Y, Zhang Q, Che X, He Y et al. 2006. Expression of elevated levels of pro-inflammatory cytokines in SARS-CoV-infected ACE2+ cells in SARS patients: relation to the acute lung injury and pathogenesis of SARS. J. Pathol. 210:28897
    [Google Scholar]
  65. 65.
    Zhang Z, Zheng Y, Niu Z, Zhang B, Wang C et al. 2021. SARS-CoV-2 spike protein dictates syncytium-mediated lymphocyte elimination. Cell Death Differ. 28:276577
    [Google Scholar]
  66. 66.
    Ziegler CGK, Miao VN, Owings AH, Navia AW, Tang Y et al. 2021. Impaired local intrinsic immunity to SARS-CoV-2 infection in severe COVID-19. Cell 184:471333.e22
    [Google Scholar]
  67. 67.
    Broggi A, Ghosh S, Sposito B, Spreafico R, Balzarini F et al. 2020. Type III interferons disrupt the lung epithelial barrier upon viral recognition. Science 369:70612
    [Google Scholar]
  68. 68.
    Cameron MJ, Bermejo-Martin JF, Danesh A, Muller MP, Kelvin DJ. 2008. Human immunopathogenesis of severe acute respiratory syndrome (SARS). Virus Res. 133:1319
    [Google Scholar]
  69. 69.
    Schaecher SR, Stabenow J, Oberle C, Schriewer J, Buller RM et al. 2008. An immunosuppressed Syrian golden hamster model for SARS-CoV infection. Virology 380:31221
    [Google Scholar]
  70. 70.
    Brocato RL, Principe LM, Kim RK, Zeng X, Williams JA et al. 2020. Disruption of adaptive immunity enhances disease in SARS-CoV-2-infected Syrian hamsters. J. Virol. 94:e01683-20
    [Google Scholar]
  71. 71.
    Graham JB, Swarts JL, Leist SR, Schäfer A, Menachery VD et al. 2021. Baseline T cell immune phenotypes predict virologic and disease control upon SARS-CoV infection in Collaborative Cross mice. PLOS Pathog. 17:e1009287
    [Google Scholar]
  72. 72.
    Boudewijns R, Thibaut HJ, Kaptein SJF, Li R, Vergote V et al. 2020. STAT2 signaling restricts viral dissemination but drives severe pneumonia in SARS-CoV-2 infected hamsters. Nat. Commun. 11:5838
    [Google Scholar]
  73. 73.
    Nouailles G, Wyler E, Pennitz P, Postmus D, Vladimirova D et al. 2021. Temporal omics analysis in Syrian hamsters unravel cellular effector responses to moderate COVID-19. Nat. Commun. 12:4869
    [Google Scholar]
  74. 74.
    Sheahan T, Morrison TE, Funkhouser W, Uematsu S, Akira S et al. 2008. MyD88 is required for protection from lethal infection with a mouse-adapted SARS-CoV. PLOS Pathog. 4:e1000240
    [Google Scholar]
  75. 75.
    Salvi V, Nguyen HO, Sozio F, Schioppa T, Gaudenzi C et al. 2021. SARS-CoV-2-associated ssRNAs activate inflammation and immunity via TLR7/8. JCI Insight 6:e150542
    [Google Scholar]
  76. 76.
    DeDiego ML, Nieto-Torres JL, Regla-Nava JA, Jimenez-Guardeño JM, Fernandez-Delgado R et al. 2014. Inhibition of NF-κB-mediated inflammation in severe acute respiratory syndrome coronavirus-infected mice increases survival. J. Virol. 88:91324
    [Google Scholar]
  77. 77.
    Zheng HY, He XY, Li W, Song TZ, Han JB et al. 2021. Pro-inflammatory microenvironment and systemic accumulation of CXCR3+ cell exacerbate lung pathology of old rhesus macaques infected with SARS-CoV-2. Signal. Transduct. Target. Ther. 6:328
    [Google Scholar]
  78. 78.
    Lin X, Fu B, Xiong Y, Xing N, Xue W et al. 2023. Unconventional secretion of unglycosylated ORF8 is critical for the cytokine storm during SARS-CoV-2 infection. PLOS Pathog. 19:e1011128
    [Google Scholar]
  79. 79.
    Yu P, Qi F, Xu Y, Li F, Liu P et al. 2020. Age-related rhesus macaque models of COVID-19. Anim. Model Exp. Med. 3:9397
    [Google Scholar]
  80. 80.
    Rosa BA, Ahmed M, Singh DK, Choreño-Parra JA, Cole J et al. 2021. IFN signaling and neutrophil degranulation transcriptional signatures are induced during SARS-CoV-2 infection. Commun. Biol. 4:290
    [Google Scholar]
  81. 81.
    Muñoz-Fontela C, Widerspick L, Albrecht RA, Beer M, Carroll MW et al. 2022. Advances and gaps in SARS-CoV-2 infection models. PLOS Pathog. 18:e1010161
    [Google Scholar]
  82. 82.
    Wang A, Chiou J, Poirion OB, Buchanan J, Valdez MJ et al. 2020. Single-cell multiomic profiling of human lungs reveals cell-type-specific and age-dynamic control of SARS-CoV2 host genes. eLife 9:e62522
    [Google Scholar]
  83. 83.
    Schuler BA, Habermann AC, Plosa EJ, Taylor CJ, Jetter C et al. 2021. Age-determined expression of priming protease TMPRSS2 and localization of SARS-CoV-2 in lung epithelium. J. Clin. Investig. 131:e140766
    [Google Scholar]
  84. 84.
    Baas T, Roberts A, Teal TH, Vogel L, Chen J et al. 2008. Genomic analysis reveals age-dependent innate immune responses to severe acute respiratory syndrome coronavirus. J. Virol. 82:946576
    [Google Scholar]
  85. 85.
    Chen J, Lau YF, Lamirande EW, Paddock CD, Bartlett JH et al. 2010. 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. 84:1289301
    [Google Scholar]
  86. 86.
    Yuan L, Zhu H, Zhou M, Ma J, Chen R et al. 2021. Gender associates with both susceptibility to infection and pathogenesis of SARS-CoV-2 in Syrian hamster. Signal. Transduct. Target Ther. 6:136
    [Google Scholar]
  87. 87.
    Dhakal S, Ruiz-Bedoya CA, Zhou R, Creisher PS, Villano JS et al. 2021. Sex differences in lung imaging and SARS-CoV-2 antibody responses in a COVID-19 golden Syrian hamster model. mBio 12:e0097421
    [Google Scholar]
  88. 88.
    Francis ME, Richardson B, Goncin U, McNeil M, Rioux M et al. 2021. Sex and age bias viral burden and interferon responses during SARS-CoV-2 infection in ferrets. Sci. Rep. 11:14536
    [Google Scholar]
  89. 89.
    Gralinski LE, Bankhead A 3rd, Jeng S, Menachery VD, Proll S et al. 2013. Mechanisms of severe acute respiratory syndrome coronavirus-induced acute lung injury. mBio 4:e00271-13
    [Google Scholar]
  90. 90.
    Cross RW, Agans KN, Prasad AN, Borisevich V, Woolsey C et al. 2020. Intranasal exposure of African green monkeys to SARS-CoV-2 results in acute phase pneumonia with shedding and lung injury still present in the early convalescence phase. Virol. J. 17:125
    [Google Scholar]
  91. 91.
    Qin Z, Liu F, Blair R, Wang C, Yang H et al. 2021. Endothelial cell infection and dysfunction, immune activation in severe COVID-19. Theranostics 11:807691
    [Google Scholar]
  92. 92.
    Suresh V, Mohanty V, Avula K, Ghosh A, Singh B et al. 2021. Quantitative proteomics of hamster lung tissues infected with SARS-CoV-2 reveal host factors having implication in the disease pathogenesis and severity. FASEB J. 35:e21713
    [Google Scholar]
  93. 93.
    Kuba K, Imai Y, Rao S, Gao H, Guo F et al. 2005. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat. Med. 11:87579
    [Google Scholar]
  94. 94.
    Yamaguchi T, Hoshizaki M, Minato T, Nirasawa S, Asaka MN et al. 2021. ACE2-like carboxypeptidase B38-CAP protects from SARS-CoV-2-induced lung injury. Nat. Commun. 12:6791
    [Google Scholar]
  95. 95.
    Damas J, Hughes GM, Keough KC, Painter CA, Persky NS et al. 2020. Broad host range of SARS-CoV-2 predicted by comparative and structural analysis of ACE2 in vertebrates. PNAS 117:2231122
    [Google Scholar]
  96. 96.
    Nieto-Torres JL, DeDiego ML, Verdiá-Báguena C, Jimenez-Guardeño JM, Regla-Nava JA et al. 2014. Severe acute respiratory syndrome coronavirus envelope protein ion channel activity promotes virus fitness and pathogenesis. PLOS Pathog. 10:e1004077
    [Google Scholar]
  97. 97.
    Jimenez-Guardeño JM, Nieto-Torres JL, DeDiego ML, Regla-Nava JA, Fernandez-Delgado R et al. 2014. The PDZ-binding motif of severe acute respiratory syndrome coronavirus envelope protein is a determinant of viral pathogenesis. PLOS Pathog. 10:e1004320
    [Google Scholar]
  98. 98.
    Honrubia JM, Gutierrez-Álvarez J, Sanz-Bravo A, González-Miranda E, Muñoz-Santos D et al. 2023. SARS-CoV-2-mediated lung edema and replication are diminished by cystic fibrosis transmembrane conductance regulator modulators. mBio 14:e0313622
    [Google Scholar]
  99. 99.
    Xia B, Shen X, He Y, Pan X, Liu FL et al. 2021. SARS-CoV-2 envelope protein causes acute respiratory distress syndrome (ARDS)-like pathological damages and constitutes an antiviral target. Cell Res. 31:84760
    [Google Scholar]
  100. 100.
    Pfefferle S, Krähling V, Ditt V, Grywna K, Mühlberger E, Drosten C. 2009. Reverse genetic characterization of the natural genomic deletion in SARS-coronavirus strain Frankfurt-1 open reading frame 7b reveals an attenuating function of the 7b protein in-vitro and in-vivo. Virol. J. 6:131
    [Google Scholar]
  101. 101.
    Silvas JA, Vasquez DM, Park JG, Chiem K, Allué-Guardia A et al. 2021. Contribution of SARS-CoV-2 accessory proteins to viral pathogenicity in K18 human ACE2 transgenic mice. J. Virol. 95:e0040221
    [Google Scholar]
  102. 102.
    Li W, Moore MJ, Vasilieva N, Sui J, Wong SK et al. 2003. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 426:45054
    [Google Scholar]
  103. 103.
    Hoffmann M, Kleine-Weber H, Schroeder S, Kruger N, Herrler T et al. 2020. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 181:27180.e8
    [Google Scholar]
  104. 104.
    Mykytyn AZ, Breugem TI, Geurts MH, Beumer J, Schipper D et al. 2023. SARS-CoV-2 Omicron entry is type II transmembrane serine protease-mediated in human airway and intestinal organoid models. J. Virol. 97:e0085123
    [Google Scholar]
  105. 105.
    Lamers MM, Mykytyn AZ, Breugem TI, Wang Y, Wu DC et al. 2021. Human airway cells prevent SARS-CoV-2 multibasic cleavage site cell culture adaptation. eLife 10:e66815
    [Google Scholar]
  106. 106.
    Zhou B, Thao TTN, Hoffmann D, Taddeo A, Ebert N et al. 2021. SARS-CoV-2 spike D614G change enhances replication and transmission. Nature 592:12227
    [Google Scholar]
  107. 107.
    Sungnak W, Huang N, Becavin C, Berg M, Queen R et al. 2020. SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes. Nat. Med. 26:68187
    [Google Scholar]
  108. 108.
    Brann DH, Tsukahara T, Weinreb C, Lipovsek M, Van den Berge K et al. 2020. Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia. Sci. Adv. 6:eabc5801
    [Google Scholar]
  109. 109.
    Muus C, Luecken MD, Eraslan G, Sikkema L, Waghray A et al. 2021. Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics. Nat. Med. 27:54659
    [Google Scholar]
  110. 110.
    Zhou L, Niu Z, Jiang X, Zhang Z, Zheng Y et al. 2020. SARS-CoV-2 targets by the pscRNA profiling of ACE2, TMPRSS2 and furin proteases. iScience 23:101744
    [Google Scholar]
  111. 111.
    Ahn JH, Kim J, Hong SP, Choi SY, Yang MJ et al. 2021. Nasal ciliated cells are primary targets for SARS-CoV-2 replication in the early stage of COVID-19. J. Clin. Investig. 131:e148517
    [Google Scholar]
  112. 112.
    Lan J, Ge J, Yu J, Shan S, Zhou H et al. 2020. Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor. Nature 581:21520
    [Google Scholar]
  113. 113.
    Shang J, Ye G, Shi K, Wan Y, Luo C et al. 2020. Structural basis of receptor recognition by SARS-CoV-2. Nature 581:22124
    [Google Scholar]
  114. 114.
    Wrapp D, Wang N, Corbett KS, Goldsmith JA, Hsieh CL et al. 2020. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science 367:126063
    [Google Scholar]
  115. 115.
    Rawat P, Jemimah S, Ponnuswamy PK, Gromiha MM 2021. Why are ACE2 binding coronavirus strains SARS-CoV/SARS-CoV-2 wild and NL63 mild?. Proteins 89:38998
    [Google Scholar]
  116. 116.
    Lima Neto JX, Vieira DS, de Andrade J, Fulco UL 2022. Exploring the Spike-hACE 2 residue-residue interaction in human coronaviruses SARS-CoV-2, SARS-CoV, and HCoV-NL63. J. Chem. Inf. Model. 62:285768
    [Google Scholar]
  117. 117.
    Li W, Zhang C, Sui J, Kuhn JH, Moore MJ et al. 2005. Receptor and viral determinants of SARS-coronavirus adaptation to human ACE2. EMBO J. 24:163443
    [Google Scholar]
  118. 118.
    Mykytyn AZ, Breugem TI, Riesebosch S, Schipper D, van den Doel PB et al. 2021. SARS-CoV-2 entry into human airway organoids is serine protease-mediated and facilitated by the multibasic cleavage site. eLife 10:e66815
    [Google Scholar]
  119. 119.
    Johnson BA, Xie X, Bailey AL, Kalveram B, Lokugamage KG et al. 2021. Loss of furin cleavage site attenuates SARS-CoV-2 pathogenesis. Nature 591:29399
    [Google Scholar]
  120. 120.
    Reinke LM, Spiegel M, Plegge T, Hartleib A, Nehlmeier I et al. 2017. Different residues in the SARS-CoV spike protein determine cleavage and activation by the host cell protease TMPRSS2. PLOS ONE 12:e0179177
    [Google Scholar]
  121. 121.
    Fraser BJ, Beldar S, Seitova A, Hutchinson A, Mannar D et al. 2022. Structure and activity of human TMPRSS2 protease implicated in SARS-CoV-2 activation. Nat. Chem. Biol. 18:96371
    [Google Scholar]
  122. 122.
    Ou T, Mou H, Zhang L, Ojha A, Choe H, Farzan M. 2021. Hydroxychloroquine-mediated inhibition of SARS-CoV-2 entry is attenuated by TMPRSS2. PLOS Pathog. 17:e1009212
    [Google Scholar]
  123. 123.
    Buchrieser J, Dufloo J, Hubert M, Monel B, Planas D et al. 2020. Syncytia formation by SARS-CoV-2-infected cells. EMBO J. 39:e106267
    [Google Scholar]
  124. 124.
    Beucher G, Blondot ML, Celle A, Pied N, Recordon-Pinson P et al. 2022. Bronchial epithelia from adults and children: SARS-CoV-2 spread via syncytia formation and type III interferon infectivity restriction. PNAS 119:e2202370119
    [Google Scholar]
  125. 125.
    Laporte M, Raeymaekers V, Van Berwaer R, Vandeput J, Marchand-Casas I et al. 2021. The SARS-CoV-2 and other human coronavirus spike proteins are fine-tuned towards temperature and proteases of the human airways. PLOS Pathog. 17:e1009500
    [Google Scholar]
  126. 126.
    Fuentes-Prior P. 2021. Priming of SARS-CoV-2 S protein by several membrane-bound serine proteinases could explain enhanced viral infectivity and systemic COVID-19 infection. J. Biol. Chem. 296:100135
    [Google Scholar]
  127. 127.
    Gordon DE, Hiatt J, Bouhaddou M, Rezelj VV, Ulferts S et al. 2020. Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms. Science 370:6521eabe940
    [Google Scholar]
  128. 128.
    Stukalov A, Girault V, Grass V, Karayel O, Bergant V et al. 2021. Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV. Nature 594:24652
    [Google Scholar]
  129. 129.
    Huang J, Hume AJ, Abo KM, Werder RB, Villacorta-Martin C et al. 2020. SARS-CoV-2 infection of pluripotent stem cell-derived human lung alveolar type 2 cells elicits a rapid epithelial-intrinsic inflammatory response. Cell Stem Cell 27:96273.e7
    [Google Scholar]
  130. 130.
    Lamers MM, van der Vaart J, Knoops K, Riesebosch S, Breugem TI et al. 2021. An organoid-derived bronchioalveolar model for SARS-CoV-2 infection of human alveolar type II-like cells. EMBO J. 40:e105912
    [Google Scholar]
  131. 131.
    Li C, Huang J, Yu Y, Wan Z, Chiu MC et al. 2023. Human airway and nasal organoids reveal escalating replicative fitness of SARS-CoV-2 emerging variants. PNAS 120:e2300376120
    [Google Scholar]
  132. 132.
    Muth D, Corman VM, Roth H, Binger T, Dijkman R et al. 2018. Attenuation of replication by a 29 nucleotide deletion in SARS-coronavirus acquired during the early stages of human-to-human transmission. Sci. Rep. 8:15177
    [Google Scholar]
  133. 133.
    V'Kovski P, Gultom M, Kelly JN, Steiner S, Russeil J et al. 2021. Disparate temperature-dependent virus-host dynamics for SARS-CoV-2 and SARS-CoV in the human respiratory epithelium. PLOS Biol. 19:e3001158
    [Google Scholar]
  134. 134.
    Chua RL, Lukassen S, Trump S, Hennig BP, Wendisch D et al. 2020. COVID-19 severity correlates with airway epithelium-immune cell interactions identified by single-cell analysis. Nat. Biotechnol. 38:97079
    [Google Scholar]
  135. 135.
    Pizzorno A, Padey B, Julien T, Trouillet-Assant S, Traversier A et al. 2020. Characterization and treatment of SARS-CoV-2 in nasal and bronchial human airway epithelia. Cell Rep. Med. 1:100059
    [Google Scholar]
  136. 136.
    Hatton CF, Botting RA, Duenas ME, Haq IJ, Verdon B et al. 2021. Delayed induction of type I and III interferons mediates nasal epithelial cell permissiveness to SARS-CoV-2. Nat. Commun. 12:7092
    [Google Scholar]
  137. 137.
    Jia HP, Look DC, Shi L, Hickey M, Pewe L et al. 2005. ACE2 receptor expression and severe acute respiratory syndrome coronavirus infection depend on differentiation of human airway epithelia. J. Virol. 79:1461421
    [Google Scholar]
  138. 138.
    Fang Y, Liu H, Huang H, Li H, Saqi A et al. 2020. Distinct stem/progenitor cells proliferate to regenerate the trachea, intrapulmonary airways and alveoli in COVID-19 patients. Cell Res. 30:7057
    [Google Scholar]
  139. 139.
    Chu H, Chan JF, Wang Y, Yuen TT, Chai Y et al. 2020. Comparative replication and immune activation profiles of SARS-CoV-2 and SARS-CoV in human lungs: an ex vivo study with implications for the pathogenesis of COVID-19. Clin. Infect. Dis. 71:14009
    [Google Scholar]
  140. 140.
    Katsura H, Sontake V, Tata A, Kobayashi Y, Edwards CE et al. 2020. Human lung stem cell-based alveolospheres provide insights into SARS-CoV-2-mediated interferon responses and pneumocyte dysfunction. Cell Stem Cell 27:890904.e8
    [Google Scholar]
  141. 141.
    Mulay A, Konda B, Garcia G Jr., Yao C, Beil S et al. 2021. SARS-CoV-2 infection of primary human lung epithelium for COVID-19 modeling and drug discovery. Cell Rep. 35:109055
    [Google Scholar]
  142. 142.
    Mossel EC, Wang J, Jeffers S, Edeen KE, Wang S et al. 2008. SARS-CoV replicates in primary human alveolar type II cell cultures but not in type I-like cells. Virology 372:12735
    [Google Scholar]
  143. 143.
    Qian Z, Travanty EA, Oko L, Edeen K, Berglund A et al. 2013. Innate immune response of human alveolar type II cells infected with severe acute respiratory syndrome-coronavirus. Am. J. Respir. Cell Mol. Biol. 48:74248
    [Google Scholar]
  144. 144.
    Chu H, Chan JF, Yuen TT, Shuai H, Yuan S et al. 2020. Comparative tropism, replication kinetics, and cell damage profiling of SARS-CoV-2 and SARS-CoV with implications for clinical manifestations, transmissibility, and laboratory studies of COVID-19: an observational study. Lancet Microbe 1:e1423
    [Google Scholar]
  145. 145.
    Yoshikawa T, Hill T, Li K, Peters CJ, Tseng CT. 2009. Severe acute respiratory syndrome (SARS) coronavirus-induced lung epithelial cytokines exacerbate SARS pathogenesis by modulating intrinsic functions of monocyte-derived macrophages and dendritic cells. J. Virol. 83:303948
    [Google Scholar]
  146. 146.
    Dalskov L, Mohlenberg M, Thyrsted J, Blay-Cadanet J, Poulsen ET et al. 2020. SARS-CoV-2 evades immune detection in alveolar macrophages. EMBO Rep. 21:e51252
    [Google Scholar]
  147. 147.
    Chin. SARS Mol. Epidemiol. Consort. 2004. Molecular evolution of the SARS coronavirus during the course of the SARS epidemic in China. Science 303:166669
    [Google Scholar]
  148. 148.
    Smits SL, de Lang A, van den Brand JMA, Leijten LM, van IJcken WF et al. 2010. Exacerbated innate host response to SARS-CoV in aged non-human primates. PLOS Pathog. 6:e1000756
    [Google Scholar]
/content/journals/10.1146/annurev-pathol-052620-121224
Loading
/content/journals/10.1146/annurev-pathol-052620-121224
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error