Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1
Spiros Vlahopoulos
 + 1631 word(s) 1631 2021-11-15 05:02:05 |
2 corrected the format
Dean Liu
 Meta information modification 1631 2021-11-30 01:47:21 |

Video Upload Options

We provide professional Video Production Services to translate complex research into visually appealing presentations. Would you like to try it?
No, upload directly Yes

Confirm

Are you sure to Delete?
Yes No
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Vlahopoulos, S. Effects of Respiratory Viruses on the Bronchial Endothelium. Encyclopedia. Available online: https://encyclopedia.pub/entry/16524 (accessed on 27 December 2024).
Vlahopoulos S. Effects of Respiratory Viruses on the Bronchial Endothelium. Encyclopedia. Available at: https://encyclopedia.pub/entry/16524. Accessed December 27, 2024.
Vlahopoulos, Spiros. "Effects of Respiratory Viruses on the Bronchial Endothelium" Encyclopedia, https://encyclopedia.pub/entry/16524 (accessed December 27, 2024).
Vlahopoulos, S. (2021, November 29). Effects of Respiratory Viruses on the Bronchial Endothelium. In Encyclopedia. https://encyclopedia.pub/entry/16524
Vlahopoulos, Spiros. "Effects of Respiratory Viruses on the Bronchial Endothelium." Encyclopedia. Web. 29 November, 2021.
Effects of Respiratory Viruses on the Bronchial Endothelium
Edit
This entry is adapted from the peer-reviewed paper 10.3390/cells10113067

Endothelial cells (ECs) comprise the inner surface of blood vessels as a single-cell layer that has the function of a semi-permeable barrier between circulating blood and underlying tissue; with a similar function in lymphatic vessels. ECs largely influence the spectrum of tissues that a virus can reach via circulation. ECs are effectors of the host response to viral infections; however, activation of host response to viruses occurs both in infected as well as uninfected cells, due to the diffusion of second messengers across intercellular gap junctions, and the secretion of paracrine mediators

respiratory syncytial virus influenza H1N1 SARS-CoV-2

1. Respiratory Syncytial Virus

Infections by RSV are a formidable threat for certain groups of patients, especially newborns and elderly [1][2]. It is a single stranded, negative-sense enveloped RNA virus belonging to the Orthopneumovirus genus of thePneumoviridae family [3]. RSV replicates in the nasopharynx and then spreads within the epithelium of bronchi and bronchiole by cell-to-cell and producing clinical features including bronchiolitis and pneumonia [4][5][6]. RSV also productively infects non-epithelial cells; thus, it been isolated from alveolar endothelium, myocardial tissue, central nervous system, cerebrospinal fluid, endocrines and liver, during severe disease and sudden infant death [7][8][9][10]. There is no effective treatment or vaccine available for RSV; palivizumab (a humanized monoclonal antibody) is the only RSV immunoprophylaxis approved for use in specific high-risk pediatric populations [11]. The therapy is mostly supportive care combined with symptomatic treatments including modalities such as bronchodilators, epinephrine, corticosteroids, hypertonic saline, and/or supplemental oxygen [12][13].
Newborns cannot be expected to mount a sufficiently strong secretion of IFNs to respond against RSV, while the elderly do not respond well to vaccinations in general [14]. There are vaccine candidates under development, yet it remains a major challenge to immunize certain population categories [15]. It is imperative that therapies are developed to protect patients that either have not been vaccinated or cannot mount an optimal immune response to RSV. RSV infection causes respiratory symptoms that may encompass the lower respiratory tract, culminating in bronchiolitis, which in severe cases results in necrosis and the sloughing of epithelial cells into the airways, airway mucus, edema, and peribronchiolar inflammation, cumulatively resulting in airway obstruction [16][17][18]. Severe bronchiolitis is associated with the manifestation of asthma in later life [18]. Epithelial cells express cytokines IL-33, IL-25, and thymic stromal lymphopoietin (TSLP), as well as the innate immune cell-derived cytokine high mobility group box 1 (HMGB1), which activate group 2 innate lymphoid cells (ILC2). This signaling promotes the progression of T-helper type 2-mediated pulmonary disease, thus explaining the association of RSV with asthma in later life.
In vitro and in vivo experiments show that during RSV infection, epithelial cells infected with RSV express and secrete IL-1α, which activates vascular endothelial cells to express increased cell surface ICAM-1, and to a lesser extent, vascular adhesion molecule-1 (VCAM-1) and E-selectin [19]. RSV induces expression of MIP-1α in epithelial cells of the alveoli and bronchioles, as well as in adjoining capillary endothelium [20]. Adhesion experiments using polymorphonuclear leukocytes (PMN) verified an increased ICAM-1-dependent adhesion rate of PMN co-cultured with RSV-infected endothelial cells. Furthermore, the increased adhesiveness resulted in an enhanced transmigration rate of PMN [21]. ICAM-1 expression on RSV-infected endothelial cells may contribute to the enhanced accumulation of PMN into the bronchoalveolar space. The virus-induced ICAM-1 upregulation was dependent on the activity of protein kinase C, protein kinase A, phosphatidylinositol 3-kinase (PI3K), and p38 mitogen-activated protein kinase (MAPK) [21].
In lung alveoli, a gradient of CXCL8 is the most likely chemo-attractant for the neutrophils that migrate from the systemic circulation into the alveolar space [22]. Neutrophils function by releasing reactive oxygen species (ROS) and extracellular traps, undergoing degranulation and phagocytosis, and by recruiting other cell types to the site of infection such as alveolar macrophages, dendritic cells, and T-cells [23]. However, soluble endothelial cell adhesion molecules (sCAMs), such as sICAM-1, can be measured in the systemic circulation, indicating that the currently postulated neutrophil influx into the lungs should rather be regarded as a neutrophil efflux from the vasculature, involving substantial neutrophil-endothelial interactions. Endothelial cells become activated upon RSV infection, driving a ‘pro-adhesive state’ for circulating neutrophils with upregulation of endothelial ICAM-1. During RSV lower respiratory tract infections, different subsets of immature and mature neutrophils are present in the bloodstream, parallel with upregulation of integrins, lymphocyte-function associated (LFA)-1 and macrophage (Mac)-1 antigen, serving as ICAM-1 ligands [22].
RSV infection induces ROS generation, activates mitogen- and stress-activated kinases-1 (MSK1)-phospho-Ser-276 v-relreticuloendotheliosis viral oncogene homolog A (RelA) pathway required for cytokine expression [24]. Aero-allergens and respiratory viruses stimulate toll-like receptor (TLR) signaling, producing oxidative injury and inflammation [25]. Repetitive exacerbations produce complex mucosal adaptations, cell-state changes, and structural remodeling. These structural changes produce substantial morbidity, decrease lung capacity, and impair quality of life. Repetitive activation of innate signaling pathways produces a form of epigenetic ‘training’ in the cell nucleus, to induce adaptive epithelial responses [25].

2. Influenza Virus and SARS-CoV-2

Influenza viruses have a single negative-stranded segmented RNA genome; deadliest in history is H1N1, an Alphainfluenzavirus of the family Orthomyxoviridae [26][27]. SARS-CoV-2 in contrast, the causative agent of the COVID-19 pandemic, belongs to the positive-strand RNA viruses of the genus Beta coronavirus [28]. Both viruses constitute very significant health burdens worldwide, due to the lack of effective treatments, and are still under research for the generation of vaccines that will offer lasting protection against emerging variants [29][30]. In influenza virus infection, pulmonary endothelial cells play a central role in regulating both innate immune cell recruitment as well as innate cytokine and chemokine production [31]. In victims of the 2009 pandemic influenza A/H1N1 infection, tissues of bronchial mucosa, lung, myocardium, gastrocnemius, and liver that were investigated by light microscopy and transmission electron microscopy, viral particles were found in all samples, frequently located in endothelium, epithelium, and muscle cells [32]. Cultured ECs respond to infection and iron incubation with increased production of IL-6. Iron, the generation of intracellular hydroxyl radical and NF-κB activity are essential in cellular activation, suggesting that ROS generated in the Haber–Weiss reaction are essential in invoking an immunological response to infection by ECs [33].
In patients who died from SARS-CoV-2 or influenza (H1N1)-associated respiratory failure, the histologic pattern in the peripheral lung was diffuse alveolar damage with perivascular T-cell infiltration. The lungs from patients with COVID-19 also showed distinctive vascular features, consisting of severe endothelial injury associated with the presence of intracellular virus and disrupted cell membranes. Histologic analysis of pulmonary vessels in patients with COVID-19 showed widespread thrombosis with microangiopathy. Alveolar capillary micro-thrombi were 9 times as prevalent in patients with COVID-19 as in patients with influenza (p < 0.001). In lungs from patients with COVID-19, the amount of new vessel growth—predominantly through a mechanism of intussusceptive angiogenesis—was 2.7 times as high as that in the lungs from patients with influenza (p < 0.001) [34].
Although respiratory viruses initially infect the airway epithelium, it is a compromise in vascular integrity that causes alveolar damage [31]. Indeed, the compromise in vascular integrity distinguishes influenza H1N1 from SARS-CoV-2 infections, and this divergence in effects can be attributed to difference in the patterns of expression and secretion of inflammatory mediators. The main difference between influenza and SARS-CoV-2 infections is the ability of SARS-CoV-2 to elicit dysfunction of the blood vessels. This difference can be attributed to a divergent expression of signaling molecules that cause the pathology that involves blood vessels. A comparison between immunological factors produced during the influenza and SARS-CoV-2 infection suggests that although both infections raise levels of T-helper type I mediators, SARS-CoV-2 also distinctly increases T-helper type II (Th2) mediators (IL-4, IL-5, IL-10, IL-13), as well as the allergy mediator [35]. In contrast, H1N1 severe cases show high expression of surfactant protein D at the alveolar epithelium [35]. H1N1 infections have shown more efficient activation of reparative macrophages of the M2 subtype [36]. This might suggest a more efficient repair capacity for the H1N1-infected lung.
One hypothesis is that severe SARS-CoV-2-driven pneumonia causes respiratory failure via pulmonary microthrombi and endothelial dysfunction [37]. A considerable body of evidence suggests that SARS-CoV-2, unlike other related viruses, infects and replicates within ECs, which may explain a significant portion of the observed clinical pathology [38][39]. On the contrary, certain data that show an inability of SARS-CoV-2 to directly infect and lyse endothelial cells without angiotensin-converting enzyme-2 (ACE2) expression explain the lack of vascular hemorrhage in COVID-19 patients and indicate that the endothelium is not a primary target of SARS-CoV-2 infection [40]. Although the detection of SARS-CoV-2 has not been singularly linked to bronchiolitis, with the exception of necrotizing bronchiolitis [41], it has been proposed that co-infections of SARS-CoV2 with other viruses, most notably RSV, are associated with a severe course of bronchiolitis in patients [42]. Furthermore, SARS-CoV-2 can directly infect engineered human blood-vessel organoids in vitro. EC involvement was demonstrated across vascular beds of different organs in a series of patients with COVID-19 and SARS-CoV-2 can directly infect engineered human blood-vessel organoids in vitro [43].
The binding site of the SARS-CoV-2 viral spike protein on the surface of cells is the receptor “angiotensin converting enzyme 2 (ACE2)”, which functions to protect against hypertension, cardiovascular and lung diseases, and diabetes mellitus [44]. In an experimental setting, loss of ACE2 function in the mouse lung during endotoxin inhalation led to release of inflammatory chemokines such as C-X-C motif chemokine 5 (CXCL5), macrophage inflammatory protein-2 (MIP2), C-X-C motif chemokine 1 (KC), and pluripotent cytokine TNF-α from airway epithelia, increased neutrophil infiltration, and exaggerated lung inflammation and injury [45]. By immunohistochemistry, flow cytometry and RNA sequencing, the lung could show expression of ACE2, mainly in alveolar macrophages, and subsets of type II alveolar epithelial cells [46][47][48][49][50].
SARS-CoV-2 infection can result in diverse, multiorgan pathology, the most significant being in the lungs (diffuse alveolar damage in its different phases, micro-thrombi, bronchopneumonia, necrotizing bronchiolitis, viral pneumonia), heart (lymphocytic myocarditis), kidney (acute tubular injury), central nervous system (micro-thrombi, ischemic necrosis, acute hemorrhagic infarction, congestion, and vascular edema), lymph nodes (hemophagocytosis and histiocytosis), bone marrow, and vasculature (deep vein thrombosis) [41].

References

  1. Chatterjee, A.; Mavunda, K.; Krilov, L.R. Current State of Respiratory Syncytial Virus Disease and Management. Infect. Dis. Ther. 2021, 1–12.
  2. Chatzis, O.; Darbre, S.; Pasquier, J.; Meylan, P.; Manuel, O.; Aubert, J.D.; Beck-Popovic, M.; Masouridi-Levrat, S.; Ansari, M.; Kaiser, L.; et al. Burden of severe RSV disease among immunocompromised children and adults: A 10 year retrospective study. BMC Infect. Dis. 2018, 18, 1–9.
  3. Rima, B.; Collins, P.; Easton, A.; Fouchier, R.; Kurath, G.; Lamb, R.A.; Lee, B.; Maisner, A.; Rota, P.; Wang, L.; et al. ICTV Virus Taxonomy Profile: Pneumoviridae. J. Gen. Virol. 2017, 98, 2912–2913.
  4. Brasier, A.R. RSV Reprograms the CDK9•BRD4 Chromatin Remodeling Complex to Couple Innate Inflammation to Airway Remodeling. Viruses 2020, 12, 472.
  5. Welliver, T.P.; Garofalo, R.P.; Hosakote, Y.; Hintz, K.H.; Avendano, L.; Sanchez, K.; Velozo, L.; Jafri, H.; Chavez-Bueno, S.; Ogra, P.L.; et al. Severe Human Lower Respiratory Tract Illness Caused by Respiratory Syncytial Virus and Influenza Virus Is Characterized by the Absence of Pulmonary Cytotoxic Lymphocyte Responses. J. Infect. Dis. 2007, 195, 1126–1136.
  6. Bennett, B.L.; Garofalo, R.P.; Cron, S.G.; Hosakote, Y.M.; Atmar, R.L.; Macias, C.G.; Piedra, P.A. Immunopathogenesis of Respiratory Syncytial Virus Bronchiolitis. J. Infect. Dis. 2007, 195, 1532–1540.
  7. Zlateva, K.T.; Van Ranst, M. DETECTION OF SUBGROUP B RESPIRATORY SYNCYTIAL VIRUS IN THE CEREBROSPINAL FLUID OF A PATIENT WITH RESPIRATORY SYNCYTIAL VIRUS PNEUMONIA. Pediatr. Infect. Dis. J. 2004, 23, 1065–1066.
  8. E Bowles, N.; Ni, J.; Kearney, D.L.; Pauschinger, M.; Schultheiss, H.-P.; McCarthy, R.; Hare, J.; Bricker, J.; Bowles, K.R.; A Towbin, J. Detection of viruses in myocardial tissues by polymerase chain reaction: Evidence of adenovirus as a common cause of myocarditis in children and adults. J. Am. Coll. Cardiol. 2003, 42, 466–472.
  9. Nadal, D.; Wunderli, W.; Meurmann, O.; Briner, J.; Hirsig, J. Isolation of Respiratory Syncytial Virus from Liver Tissue and Extrahepatic Biliary Atresia Material. Scand. J. Infect. Dis. 1990, 22, 91–93.
  10. Gkentzi, D.; Dimitriou, G.; Karatza, A. Non-pulmonary manifestations of respiratory syncytial virus infection. J. Thorac. Dis. 2018, 10, S3815–S3818.
  11. Eiland, L.S. Respiratory Syncytial Virus: Diagnosis, Treatment and Prevention. J. Pediatr. Pharmacol. Ther. 2009, 14, 75–85.
  12. Ralston, S.L.; Lieberthal, A.S.; Meissner, H.C.; Alverson, B.K.; Baley, J.E.; Gadomski, A.M.; Johnson, D.W.; Light, M.J.; Maraqa, N.F.; Mendonca, E.A.; et al. Clinical Practice Guideline: The Diagnosis, Management, and Prevention of Bronchiolitis. Pediatrics 2014, 134, e1474–e1502.
  13. Barr, R.; Green, C.A.; Sande, C.J.; Drysdale, S.B. Respiratory syncytial virus: Diagnosis, prevention and management. Ther. Adv. Infect. Dis. 2019, 6.
  14. Beijnen, E.M.S.; Van Haren, S.D. Vaccine-Induced CD8+ T Cell Responses in Children: A Review of Age-Specific Molecular Determinants Contributing to Antigen Cross-Presentation. Front. Immunol. 2020, 11, 607977.
  15. Biagi, C.; Dondi, A.; Scarpini, S.; Rocca, A.; Vandini, S.; Poletti, G.; Lanari, M. Current State and Challenges in Developing Respiratory Syncytial Virus Vaccines. Vaccines 2020, 8, 672.
  16. Walsh, E.E. Respiratory Syncytial Virus Infection. Clin. Chest Med. 2016, 38, 29–36.
  17. E Johnson, J.; A Gonzales, R.; Olson, S.J.; Wright, P.F.; Graham, B.S. The histopathology of fatal untreated human respiratory syncytial virus infection. Mod. Pathol. 2006, 20, 108–119.
  18. Norlander, A.E.; Peebles, R.S., Jr. Innate Type 2 Responses to Respiratory Syncytial Virus Infection. Viruses 2020, 12, 521.
  19. Chang, C.-H.; Huang, Y.; Anderson, R. Activation of vascular endothelial cells by IL-1α released by epithelial cells infected with respiratory syncytial virus. Cell. Immunol. 2003, 221, 37–41.
  20. Haeberle, H.A.; Kuziel, W.A.; Dieterich, H.-J.; Casola, A.; Gatalica, Z.; Garofalo, R.P. Inducible Expression of Inflammatory Chemokines in Respiratory Syncytial Virus-Infected Mice: Role of MIP-1α in Lung Pathology. J. Virol. 2001, 75, 878–890.
  21. Arnold, R.; Nig, W.K. Respiratory Syncytial Virus Infection of Human Lung Endothelial Cells Enhances Selectively Intercellular Adhesion Molecule-1 Expression. J. Immunol. 2005, 174, 7359–7367.
  22. Juliana, A.; Zonneveld, R.; Plötz, F.B.; van Meurs, M.; Wilschut, J. Neutrophil-endothelial interactions in respiratory syncytial virus bronchiolitis: An understudied aspect with a potential for prediction of severity of disease. J. Clin. Virol. 2019, 123, 104258.
  23. Johansson, C.; Kirsebom, F.C.M. Neutrophils in respiratory viral infections. Mucosal Immunol. 2021, 1–13.
  24. Jamaluddin, M.; Tian, B.; Boldogh, I.; Garofalo, R.P.; Brasier, A.R. Respiratory Syncytial Virus Infection Induces a Reactive Oxygen Species-MSK1-Phospho-Ser-276 RelA Pathway Required for Cytokine Expression. J. Virol. 2009, 83, 10605–10615.
  25. Brasier, A.R.; Boldogh, I. Targeting inducible epigenetic reprogramming pathways in chronic airway remodeling. Drugs Context 2019, 8, 1–10.
  26. Muramoto, Y.; Takada, A.; Fujii, K.; Noda, T.; Iwatsuki-Horimoto, K.; Watanabe, S.; Horimoto, T.; Kida, H.; Kawaoka, Y. Hierarchy among Viral RNA (vRNA) Segments in Their Role in vRNA Incorporation into Influenza A Virions. J. Virol. 2006, 80, 2318–2325.
  27. Zhuang, Q.; Wang, S.; Liu, S.; Hou, G.; Li, J.; Jiang, W.; Wang, K.; Peng, C.; Liu, D.; Guo, A.; et al. Diversity and distribution of type A influenza viruses: An updated panorama analysis based on protein sequences. Virol. J. 2019, 16, 1–38.
  28. Coronaviridae Study Group of the International Committee on Taxonomy of Viruses The species Severe acute respiratory syndrome-related coronavirus: Classifying 2019-nCoV and naming it SARS-CoV-2. Nat. Microbiol. 2020, 5, 536–544.
  29. Moore, K.A.; Ostrowsky, J.T.; Kraigsley, A.M.; Mehr, A.J.; Bresee, J.S.; Friede, M.H.; Gellin, B.G.; Golding, J.P.; Hart, P.J.; Moen, A.; et al. A Research and Development (R&D) roadmap for influenza vaccines: Looking toward the future. Vaccine 2021, 39, 6573–6584.
  30. Poland, G.A.; Ovsyannikova, I.G.; Kennedy, R.B. The need for broadly protective COVID-19 vaccines: Beyond S-only approaches. Vaccine 2021, 39, 4239–4241.
  31. Fosse, J.H.; Haraldsen, G.; Falk, K.; Edelmann, R. Endothelial Cells in Emerging Viral Infections. Front. Cardiovasc. Med. 2021, 8, 619690.
  32. Ru, Y.-X.; Li, Y.-C.; Zhao, Y.; Zhao, S.-X.; Yang, J.-P.; Zhang, H.-M.; Pang, T.-X. Multiple Organ Invasion by Viruses: Pathological Characteristics in Three Fatal Cases of the 2009 Pandemic Influenza A/H1N1. Ultrastruct. Pathol. 2011, 35, 155–161.
  33. Visseren, F.L.J.; Verkerk, M.S.A.; Van Der Bruggen, T.; Marx, J.J.M.; Van Asbeck, B.S.; Diepersloot, R.J.A. Iron chelation and hydroxyl radical scavenging reduce the inflammatory response of endothelial cells after infection with Chlamydia pneumoniae or influenza A. Eur. J. Clin. Investig. 2002, 32, 84–90.
  34. Ackermann, M.; Verleden, S.; Kuehnel, M.; Haverich, A.; Welte, T.; Laenger, F.; Vanstapel, A.; Werlein, C.; Stark, H.; Tzankov, A.; et al. Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19. New Engl. J. Med. 2020, 383, 120–128.
  35. Choreño-Parra, J.A.; Jiménez-Álvarez, L.A.; Ramírez-Martínez, G.; Cruz-Lagunas, A.; Thapa, M.; Fernández-López, L.A.; Carnalla-Cortés, M.; Choreño-Parra, E.M.; Mena-Hernández, L.; Sandoval-Vega, M.; et al. Expression of Surfactant Protein D Distinguishes Severe Pandemic Influenza A(H1N1) from Coronavirus Disease 2019. J. Infect. Dis. 2021.
  36. de Paula, C.B.V.; De Azevedo, M.L.V.; Nagashima, S.; Martins, A.P.C.; Malaquias, M.A.S.; Miggiolaro, A.F.R.D.S.; Júnior, J.D.S.M.; Avelino, G.; Carmo, L.A.P.D.; Carstens, L.B.; et al. IL-4/IL-13 remodeling pathway of COVID-19 lung injury. Sci. Rep. 2020, 10, 1–8.
  37. Poor, H.D.; Ventetuolo, C.E.; Tolbert, T.; Chun, G.; Serrao, G.; Zeidman, A.; Dangayach, N.S.; Olin, J.; Kohli-Seth, R.; Powell, C.A. COVID-19 critical illness pathophysiology driven by diffuse pulmonary thrombi and pulmonary endothelial dysfunction responsive to thrombolysis. Clin. Transl. Med. 2020, 10.
  38. Oxford, A.E.; Halla, F.; Robertson, E.B.; Morrison, B.E. Endothelial Cell Contributions to COVID-19. Pathogens 2020, 9, 785.
  39. Bao, W.; Zhang, X.; Jin, Y.; Hao, H.; Yang, F.; Yin, D.; Chen, X.; Xue, Y.; Han, L.; Zhang, M. Factors Associated with the Expression of ACE2 in Human Lung Tissue: Pathological Evidence from Patients with Normal FEV1 and FEV1/FVC. J. Inflamm. Res. 2021, 14, 1677–1687.
  40. Conde, J.N.; Schutt, W.R.; Gorbunova, E.E.; Mackow, E.R. Recombinant ACE2 Expression Is Required for SARS-CoV-2 To Infect Primary Human Endothelial Cells and Induce Inflammatory and Procoagulative Responses. mBio 2020, 11.
  41. Vasquez-Bonilla, W.O.; Orozco, R.; Argueta, V.; Sierra, M.; Zambrano, L.I.; Muñoz-Lara, F.; López-Molina, D.S.; Arteaga-Livias, K.; Grimes, Z.; Bryce, C.; et al. A review of the main histopathological findings in coronavirus disease 2019. Hum. Pathol. 2020, 105, 74–83.
  42. Rotulo, G.A.; Casalini, E.; Brisca, G.; Piccotti, E.; Castagnola, E. Unexpected peak of bronchiolitis requiring oxygen therapy in February 2020: Could an undetected SARS-CoV2-RSV co-infection be the cause? Pediatr. Pulmonol. 2021, 56, 1803–1805.
  43. Monteil, V.; Kwon, H.; Prado, P.; Hagelkrüys, A.; Wimmer, R.A.; Stahl, M.; Leopoldi, A.; Garreta, E.; Del Pozo, C.H.; Prosper, F.; et al. Inhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical-Grade Soluble Human ACE2. Cell 2020, 181, 905–913.e7.
  44. Chernyak, B.V.; Popova, E.N.; Prikhodko, A.S.; Grebenchikov, O.A.; Zinovkina, L.A.; Zinovkin, R.A. COVID-19 and Oxidative Stress. Biochem. (Moscow) 2020, 85, 1543–1553.
  45. Sodhi, C.P.; Wohlford-Lenane, C.; Yamaguchi, Y.; Prindle, T.; Fulton, W.B.; Wang, S.; McCray, P.B., Jr.; Chappell, M.; Hackam, D.J.; Jia, H. Attenuation of pulmonary ACE2 activity impairs inactivation of des-Arg9 bradykinin/BKB1R axis and facilitates LPS-induced neutrophil infiltration. Am. J. Physiol. Cell. Mol. Physiol. 2018, 314, L17–L31.
  46. Song, X.; Hu, W.; Yu, H.; Zhao, L.; Zhao, Y.; Zhao, X.; Xue, H.; Zhao, Y. Little to no expression of angiotensin-converting enzyme-2 on most human peripheral blood immune cells but highly expressed on tissue macrophages. Cytom. Part A 2020.
  47. Hamming, I.; Timens, W.; Bulthuis, M.; Lely, A.; Navis, G.; van Goor, H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J. Pathol. 2004, 203, 631–637.
  48. Hikmet, F.; Méar, L.; Edvinsson, Å.; Micke, P.; Uhlén, M.; Lindskog, C. The protein expression profile of ACE2 in human tissues. Mol. Syst. Biol. 2020, 16, e9610.
  49. Ziegler, C.G.; Allon, S.J.; Nyquist, S.K.; Mbano, I.M.; Miao, V.N.; Tzouanas, C.N.; Cao, Y.; Yousif, A.; Bals, J.; Hauser, B.; et al. SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues. Cell 2020, 181, 1016–1035.e19.
  50. Zou, X.; Chen, K.; Zou, J.; Han, P.; Hao, J.; Han, Z. Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection. Front. Med. 2020, 14, 185–192.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
Upload a video for this entry
Information
Subjects: Agriculture, Dairy & Animal Science
Contributor MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Spiros Vlahopoulos
View Times: 485
Revisions: 2 times (View History)
Update Date: 30 Nov 2021
Table of Contents
    1000/1000
    Hot Most Recent
    Video Production Service
    Feedback