scholarly journals Comparative pathogenesis of COVID-19, MERS, and SARS in a nonhuman primate model

Science ◽  
2020 ◽  
Vol 368 (6494) ◽  
pp. 1012-1015 ◽  
Author(s):  
Barry Rockx ◽  
Thijs Kuiken ◽  
Sander Herfst ◽  
Theo Bestebroer ◽  
Mart M. Lamers ◽  
...  
Keyword(s):  
Diffuse Alveolar Damage ◽  
Clinical Signs ◽  
Type I ◽  
Type Ii ◽  
Nonhuman Primate Model ◽  
Primate Model ◽  
Type Ii Pneumocytes ◽  
Cynomolgus Macaques ◽  
Ciliated Epithelial Cells ◽  
Nose And Throat

The current pandemic coronavirus, severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2), was recently identified in patients with an acute respiratory syndrome, coronavirus disease 2019 (COVID-19). To compare its pathogenesis with that of previously emerging coronaviruses, we inoculated cynomolgus macaques with SARS-CoV-2 or Middle East respiratory syndrome (MERS)–CoV and compared the pathology and virology with historical reports of SARS-CoV infections. In SARS-CoV-2–infected macaques, virus was excreted from nose and throat in the absence of clinical signs and detected in type I and II pneumocytes in foci of diffuse alveolar damage and in ciliated epithelial cells of nasal, bronchial, and bronchiolar mucosae. In SARS-CoV infection, lung lesions were typically more severe, whereas they were milder in MERS-CoV infection, where virus was detected mainly in type II pneumocytes. These data show that SARS-CoV-2 causes COVID-19–like disease in macaques and provides a new model to test preventive and therapeutic strategies.

scholarly journals Comparative Pathogenesis Of COVID-19, MERS And SARS In A Non-Human Primate Model

2020 ◽  
Author(s):  
Barry Rockx ◽  
Thijs Kuiken ◽  
Sander Herfst ◽  
Theo Bestebroer ◽  
Mart M. Lamers ◽  
...  
Keyword(s):  
Diffuse Alveolar Damage ◽  
Clinical Signs ◽  
Type I ◽  
Primate Model ◽  
Type Ii Pneumocytes ◽  
Virus Excretion ◽  
Cynomolgus Macaques ◽  
Novel Coronavirus ◽  
Nose And Throat ◽  
Human Primate

AbstractA novel coronavirus, SARS-CoV-2, was recently identified in patients with an acute respiratory syndrome, COVID-19. To compare its pathogenesis with that of previously emerging coronaviruses, we inoculated cynomolgus macaques with SARS-CoV-2 or MERS-CoV and compared with historical SARS-CoV infections. In SARS-CoV-2-infected macaques, virus was excreted from nose and throat in absence of clinical signs, and detected in type I and II pneumocytes in foci of diffuse alveolar damage and mucous glands of the nasal cavity. In SARS-CoV-infection, lung lesions were typically more severe, while they were milder in MERS-CoV infection, where virus was detected mainly in type II pneumocytes. These data show that SARS-CoV-2 can cause a COVID-19-like disease, and suggest that the severity of SARS-CoV-2 infection is intermediate between that of SARS-CoV and MERS-CoV.One Sentence SummarySARS-CoV-2 infection in macaques results in COVID-19-like disease with prolonged virus excretion from nose and throat in absence of clinical signs.

Effect of tunicamycin on maturation of fetal mouse lung

1993 ◽  
Vol 265 (3) ◽  
pp. L250-L259
Author(s):  
E. H. Webster ◽  
S. R. Hilfer ◽  
R. L. Searls ◽  
J. Kornilow
Keyword(s):  
Extracellular Matrix ◽  
Fetal Lung ◽  
Mouse Lung ◽  
Type I ◽  
Type Ii ◽  
Fetal Mouse ◽  
Type Ii Pneumocytes ◽  
Separate Control ◽  
Normal Controls

The mesodermal capsule of the fetal lung plays a role in differentiation of the respiratory region. It has been proposed for other epithelial organs that the mesodermal capsule influences development by modifying the basal lamina or the extended extracellular matrix. The effect could be on deposition or turnover of collagens, proteoglycans, and/or glycoproteins. This study tests the role of glycoproteins in differentiation of respiratory endings by inhibiting their synthesis with the antibiotic tunicamycin (TM). Lungs at 16 and 18 days gestation and 3 days after birth were cultured with TM and examined for morphological and biochemical differences from normal controls. With TM, alveolar regions did not expand properly and formed fewer type I pneumocytes, although type II pneumocytes were unaffected. The epithelium of untreated respiratory regions showed greater incorporation of radioactive mannose than the airways region or mesenchyme. This incorporation was diminished in TM, but the pattern persisted. Comparison with the results obtained with beta-xyloside suggested that differentiation of type I and type II pneumocytes is under separate control.

Κοροναϊός του σκύλου: ένας όχι ‘αθώος’ ιός

2017 ◽  
Vol 64 (1) ◽  
pp. 57
Author(s):  
V. NTAFIS (Β. ΝΤΑΦΗΣ) ◽  
M. PAPANASTASSOPOULOU (Μ. ΠΑΠΑΝΑΣΤΑΣΟΠΟΥΛΟΥ) ◽  
E. XYLOURI (E.ΞΥΛΟΥΡΗ)
Keyword(s):  
Genetic Variability ◽  
Protective Efficacy ◽  
Clinical Signs ◽  
Acute Diarrhoea ◽  
Systemic Infection ◽  
Transmissible Gastroenteritis Virus ◽  
Mixed Infections ◽  
Type I ◽  
Type Ii ◽  
High Genetic Variability

Canine coronavirus (CCoV) is a significant aetiologic agent of acute diarrhoea in dogs, specially in puppies. An important characteristic of coronaviruses is their high genetic variability, due to increased mutation frequency and sporadic recombination events. Due to this genetic variability, CCoV is classified in two distinct types, type I and II. CCoV type I strains share increased genetic similarity with Feline coronavirus strains, while CCoV type II consists of the typical reference CCoVs. Moreover, type II strains are classified into one of two subtypes, which include the classical strains (CCoV-IIa) and the new strains (CCoV-IIb), which emerged as a result of recombination among CCoV and Porcine transmissible gastroenteritis virus. Typical disease signs of CCoV infection are anorexia, depression, lethargy, as well as vomiting and diarrhoea. Mortality rate is low, especially in adult dogs with no infection signs. Most dogs recover within 7-10 days. Mixed infections with other viruses, bacteria or parasites may lead to more severe clinical disease. Currently, CCoV appears to have spread worldwide and has been related to mild, acute diarrhoea. However, during the last years, novel CCoV strains associated with outbreaks of lethal gastroenteritis have been detected in Australia and Europe. Genome analysis revealed that these strains shared low similarity with prototype reference strains of CCoV, suggesting that atypical, divergent strains may be related to more severe clinical signs. In addition, over the past decade, strains with an ability to trespass the intestinal tract, leading to lethal systemic infection, have also been isolated. These strains have attracted scientific interest, with research focusing on experimental infections, identification of genetic markers and prophylaxis. Pantropic CCoV strains have been detected across Europe, suggesting that the new, highly pathogenic biotype is circulating among canine population. The high genetic variability of CCoV, the severe mixed infections  and the antigenic differences among CCoV types and subtypes raise questions regarding the protective efficacy of the currently commercially available vaccines.

Effectiveness of Cervical Hemilaminectomy in Canine Hansen Type I and Type II Disc Disease: A Retrospective Study

2011 ◽  
Vol 47 (5) ◽  
pp. 342-350 ◽  
Author(s):  
Oliver Schmied ◽  
Lorenzo Golini ◽  
Frank Steffen
Keyword(s):  
Medical Records ◽  
Cervical Vertebrae ◽  
Clinical Signs ◽  
Type I ◽  
Type Ii ◽  
Disc Disease ◽  
Disc Protrusion ◽  
Common Clinical Presentation ◽  
Disc Extrusion ◽  
Small Breed

Medical records of 41 dogs, including 15 small breed dogs (<15 kg) and 26 large breed dogs (>15 kg), with cervical intervertebral disc disease (IVDD) that underwent a hemilaminectomy were reviewed. Dogs were diagnosed using myelography, computed tomography/myelography, or MRI, and dogs were classified as having either Hansen Type I disc extrusion or Hansen Type II disc protrusion located ventrally, ventrolaterally, or laterally within the cervical spinal canal. The most common clinical presentation was ambulatory tetraparesis and/or lameness (44%). The most affected sites for cervical IVDD were between the sixth and seventh cervical vertebrae (C6–C7; 78% of Hansen Type II discs) and C2–C3 (86% of Hansen Type I discs). Treatment was effective in 88% of dogs. Five large breed dogs (12%) did not improve. In dogs with a Hansen Type I disc extrusion, clinical signs improved in 96% of the cases. In dogs with a Hansen Type II disc protrusion, an excellent and good outcome was seen in 47% and 32% of cases, respectively. Outcome was significantly better for small breed dogs and dogs with Hansen Type I disc disease compared with large breed dogs and dogs with Hansen Type II disc disease.

Three Types of Hereditary Antiterombin III Deficiency

1979 ◽  
Author(s):  
I. Nagy ◽  
H. Losonczy
Keyword(s):  
Antithrombin Iii ◽  
Clinical Signs ◽  
Type I ◽  
Type Ii ◽  
Type Iii ◽  
Basic Activity ◽  
At Iii ◽  
And Function

The authors detected in the last seven years 15 patients with hereditary antithrombin III/AT III/ abnormality. All of them had typical clinical signs of recurrent arterious and venous thromboembolie. The abnormality inherited as an autosomal trait. Three types of the abnormality could be observed. In Type I both quantity and function of AT III were extremely decreased. In type II AT III is normal in quantity but abnormal in function. In Type III AT III is quantitatively normal and also its function seems normal as far as its basic activity is concerned /activity measured in absence of heparin/, but its abnormality becomes manifest in the presence of heparin in vitro/and also in vivo/. 5 of the patients belonged to Type I, 4 to Type II and 6 to Type III. In 60 examined family members of the 15 patients an abnormal AT III could be observed in 44, clinical signs in 23.The examination of AT III activity in the presence of a given amount of heparin ia of great importance in recognition of the different types of antithrombin III abnormalities.

Putrescine uptake in hamster lung slices and primary cultures of type II pneumocytes

1995 ◽  
Vol 269 (5) ◽  
pp. L681-L689 ◽  
Author(s):  
P. H. Hoet ◽  
C. P. Lewis ◽  
D. Dinsdale ◽  
M. Demedts ◽  
B. Nemery
Keyword(s):  
Cellular Localization ◽  
Competitive Inhibition ◽  
Primary Cultures ◽  
Alveolar Epithelium ◽  
Type I ◽  
Uptake System ◽  
Type Ii ◽  
Active Uptake ◽  
Type Ii Pneumocytes ◽  
Discontinuous Percoll Gradient

Putrescine is accumulated in the lungs of various species by an active uptake system that also mediates the uptake of cystamine and paraquat. We have characterized this uptake in both lung slices and type II pneumocytes isolated from hamsters by trypsin digestion, differential adherence on plastic, and centrifugation on a discontinuous Percoll gradient. The accumulation of [14C]putrescine in lung slices was shown to be temperature and energy dependent, and to obey saturation kinetics, with mean calculated values of apparent Michaelis constant (Km) 29.4 microM and maximum rate of uptake (Vmax) 637 nmol.g-1.h-1. In the presence of cystamine or paraquat, the putrescine uptake was reduced in a manner compatible with competitive inhibition. The calculated inhibitor constants (Ki) were 16 and 1,017-1,328 microM for the inhibition by cystamine and paraquat, respectively. The cellular localization of [3H]putrescine in lung slices after incubation with 2.5 microM putrescine was determined by light-microscopic autoradiography. Labeling was present in type II and possibly also in type I pneumocytes of the alveolar epithelium but not in macrophages, endothelium, or cells of the interstitium. Two days after their isolation, cultured type II pneumocytes exhibited an uptake of putrescine that had kinetic characteristics similar to those of slices (Km of 23 microM and Vmax of 3.06 mumol.g protein-1.h-1) and was also competitively inhibited by paraquat (Ki of 222-350 microM paraquat). Our data demonstrate the presence of an active uptake system for putrescine in both lung slices and cultured type II pneumocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Differences in basement membrane-associated microdomains of type I and type II pneumocytes in the rat and rabbit lung.

1984 ◽  
Vol 32 (8) ◽  
pp. 827-833 ◽  
Author(s):  
P L Sannes
Keyword(s):  
Basement Membrane ◽  
Basement Membranes ◽  
Type I ◽  
Type Ii Cells ◽  
Type Ii ◽  
Sulfate Ester ◽  
Pulmonary Alveoli ◽  
Type I Cells ◽  
Type Ii Pneumocytes ◽  
I Cells

The basement membrane-associated microdomains of type I pneumocytes in rat and rabbit pulmonary alveoli were found to be uniquely different from those of type II pneumocytes in the specific distribution of cytochemically detectable sulfate esters as demonstrated with the high iron diamine (HID) technique at the electron microscopic level. Aldehyde-fixed frozen or Vibratome sections of neonatal and adult lungs were treated with a mixture of the meta and para isomers of N,N-dimethyl-phenylenediamine-HCl in the presence of ferric chloride, which at low pH (1.0) has been previously shown to be highly specific for sulfate esters of glycosaminoglycans and glycoproteins. Reaction product was subsequently enhanced with a thiocarbohydrazide-silver proteinate, postembedding sequence for electron microscopy. Samples of lung parenchyma treated in this fashion were observed to have discrete, electron-dense silver grains associated with the various microanatomical components of pulmonary basement membranes. In the region of the alveolar basement membrane, the lamina rara externa associated with type I cells was observed to contain an abundance of regularly disposed, cytochemically detectable sulfate esters, while the lamina densa and lamina rara interna were diffusely and sparsely reactive by comparison. Quantitatively, 62% of all reactive sites found in the basement membrane region of type I cells were localized in the lamina rara externa. By contrast, the lamina rara externa of type II cells had less than half as many reactive foci indicative of sulfate esters as the same region of type I cell basement membranes. HID-reactive sulfate esters were found evenly distributed within the laminae associated with the basement membrane of type II cells. This cytochemically detectable difference in the sulfate ester composition of basement membrane-associated sulfate ester composition of basement membrane-associated microdomains of type I compared with that of type II pneumocytes may be highly significant when considering known patterns of epithelial renewal in pulmonary alveoli. Since type II cells are known to divide and either remain type II cells or differentiate into type I cells, regional differences in the molecular composition of the alveolar basement membranes and their associated structures may be key determinants of cell-specific processes of cytodifferentiation in the pulmonary alveolus.

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