A review on the role of angiotensin-converting enzyme 2 in children with coronavirus disease 2019 / 中国当代儿科杂志

With the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) all over the world, there is an increasing number of children with such infection. Angiotensin-converting enzyme 2 (ACE2), one of the binding sites for SARS-CoV-2 infection in humans, can bind to viral spike proteins, allowing transmembrane serine protease (TMPRSS2) to activate S-protein to trigger infection and induce the production of various inflammatory factors such as interleukin-1, interferon-l, and tumor necrosis factor. Compared with adults, children tend to have lower expression levels of ACE2 and TMPRSS2, which are presumed to be associated with milder symptoms and fewer cases in children. The article summarizes the research advances in the role of ACE2 during SARS-CoV-2 infection, in order to help understand the pathogenic mechanism of SARS-CoV-2 and provide a reference for better development of drugs and vaccines to prevent and treat coronavirus disease 2019 in children.

Expression of EV71-VP1, PSGL-1 and SCARB2 in Tissues of Infants with Brain Stem Encephalitis / 法医学杂志

OBJECTIVE@#To understand the correlation of enterovirus 71 (EV71), P-selectin glycoprotein ligand-1 (PSGL-1), and scavenger receptor B2 (SCARB2) and to explore the possible pathway and mechanism of EV71 infection by observing the expression of EV71, PSGL-1 and SCARB2 in tissues of infants with brain stem encephalitis.@*METHODS@#The organs and tissues of infants with EV71-VP1 positivity in their brain stems were chosen. Expression and distribution of EV71-VP1, PSGL-1, and SCARB2 were detected and compared by immunohistochemistry.@*RESULTS@#Strong staining of EV71 -VP1 was observed in the neuron, glial cells, the inflammatory cells of perivascular cuffing, parietal cells of the gastric fundus gland while alveolar macrophages, intestinal gland epithelium cells, mucosa lymphoid nodule and lymphocyte of palatine tonsil showed moderate staining and weak staining were displayed in mesenteric lymph nodes and lymphocyte of spleen. PSGL-1 expression was detected in parietal cells of the gastric fundus gland, tonsillar crypt squamous epithelium, alveolar macrophages and leukocytes in each tissue. SCARB2 expression was observed in all the above tissues except the intestines and spleen.@*CONCLUSION@#The distribution of EV71 correlates with SCARB2 expression. SCARB2 plays an important role in virus infection and replication. Stomach may be an important site for EV71 replication.

Expression of CAR in myocardial of viral myocarditis and dilated cardiomyopathy / 法医学杂志

OBJECTIVE@#In order to improve accuracy and reliability of forensic diagnosis of sudden cardiac death, pathogenesis and relationship between the viral myocarditis (VMC) and dilated cardiomyopathy (DCM) were investigated.@*METHODS@#Improved immunohistochemical technique was used to detect the expression of the CAR in myocardium samples, including 22 deceased with VMC, 20 deceased with DCM and 16 control deceased.@*RESULTS@#The brown staining on the cell membrane of myocardium showed positive result. There was a prominent CAR expression in VMC group and DCM group, which were statistically significant difference compared with control group (P < 0.05).@*CONCLUSION@#The CAR expression showed significantly higher in VMC and DCM groups. The viral infection can result in myocardial necrosis and impaired cardiac functions. These abnormalities can trigger a cascade of events that contributed to the progress of VMC to DCM.

The expression of coxsackie B virus adenovirus receptor (CAR) in viral myocarditis and dilated cardiomyopathy patients / 法医学杂志

OBJECTIVE@#To explore etiology and pathogenesis of viral myocarditis (VMC) and dilated cardiomyopathy (DCM).@*METHODS@#The expression of Coxsackie B virus and adenovirus receptors (CAR) were detected with modified immunohistochemical (IHC) technique in myocardium of left ventricle, right ventricle, interventricular septum, and septal papillary muscle from 28 patients with viral myocarditis, 31 patients with dilated cardiomyopathy and 17 control patients (including normal, hypertension heart disease, myocardial infarction and coronary atherosclerotic heart disease).@*RESULTS@#The brown staining on the cell membrane of myocardium represents positive result. 100% (28 of 28) of VMC patients (IHC surface integral: 4.3975 +/- 0.0365) and 84% (26 of 31) of DCM patients (4.2064 +/- 0.052 6) had prevalent CAR expression compared to 0% (0 of 19) control patients (0.073 1 +/- 0.0362). There were statistically significant differences between VMC/DCM and control patients (P < 0.05).@*CONCLUSION@#The prevalence of CAR expression was significantly higher in VMC and DCM patients (100% and 84% vs. 0% in control). In contrast, there was no difference found between VMC and DCM patients. These results suggest that both VMC and DCM involve viral etiology and could share a similar pathogenesis.

In vivo characterization of the integrin beta3 as a receptor for Hantaan virus cellular entry

Binding of viruses to cell surface molecules is an essential step in viral infection. In vitro studies suggested that the alpha v beta3 integrin receptor is the epithelial cell receptor for Hantaan virus (HTNV). Whether beta3 is in vivo the only or central cellular receptor for HTNV infection is not known. To investigate the role of beta3 integrin for cellular entry of HTNV, we established an HTNV infection model in newborn murine pups. Infected pups died at an average age of 14.2 +/- 1.1 days with high levels of viral antigen detected in their brain, lung, and kidney. Pre-injection of blocking monoclonal antibodies (mAb) specific for either beta3 or av prolonged survival significantly to a maximal average survival of 19.7 +/- 1.5 days (P<0.01) and 18.4 +/- 0.9 days (P<0.01), respectively. XT-199, a chemical blocker of the alpha v beta3 receptor also prolonged survival to 19.5 +/- 1.3 days (P<0.01). In contrast to these receptor blockades, anti-HTNV antibody was not only able to prolong survival, but 20% of infected pups achieved long-term survival. An anti-murine beta1 antibody comparatively prolonged survival (19.0 +/- 1.2 days), suggesting that HTNV infection is partly mediated through integrin beta1 receptors as well as through beta3 receptors in vivo. Our data demonstrate that the beta3 receptor is important for HTNV infection in vivo, but also suggest that HTNV may utilize additional receptors beyond beta3 for cellular entry within an organism.

Identification of a putative cellular receptor 150 kDa polypeptide for porcine epidemic diarrhea virus in porcine enterocytes

Porcine epidemic diarrhea virus (PEDV) causes an acute enteritis in pigs of all ages, often fatality for neonates. PEDV occupies an intermediate position between two well characterized members of the coronavirus group I, human coronavirus (HCoV-229E)and transmissible gastroenteritis virus (TGEV) which uses aminopeptidase N (APN), a 150 kDa protein, as their receptors. However, the receptor of the PEDV has not been identified yet. A virus overlay protein binding assay (VOPBA) was used to identify PEDV binding protein in permissive cells. The binding ability of PEDV to porcine APN (pAPN) and the effects of pAPN on infectivity of PEDV in Vero cells were also investigated. VOPBA identified a 150 kDa protein, as a putative PEDV receptor in enterocytes and swine testicle (ST) cells. Further the PEDV binding to pAPN was blocked by anti-pAPN and pAPN enhanced PEDV infectivity in Vero cells. In conclusion, these results suggested that pAPN may act as a receptor of PEDV.

Putative chikungunya virus-specific receptor proteins on the midgut brush border membrane of Aedes aegypti mosquito.

Two proteins (putative receptors) of 60 and 38 kDa, for chikungunya (CHIK) virus were detected in the brush border membrane fraction (BBMF) of the normal population of Aedes aegypti mosquitoes. Mosquitoes were infected orally with CHIK virus and infectivity checked by testing the head squashes. BBMF was prepared from proved positive and negative mosquitoes. The receptor proteins were found to be present in both the proved genotypes. However, dot-b'ot assays showed that the CHIK virus binding activity of BBMF/mg protein was noticeably low in the proved negative mosquitoes as compared to the positives. BBMF from the larvae of the normal populations also showed the presence of the receptor proteins, binding to CHIK virus. Receptor proteins from larvae as well as the adults were found glycosylated. CHIK virus receptor proteins of 24, 45, 58, 60 and 62 kDa were also seen in the membrane fraction of the C6/36 cells.