Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Subacute sclerosing panencephalitis(SSPE) is a progressive and fatal neurological illness without established treatment. As the precise mechanism how measles virus (MV) causes SSPE is still unknown, full clarification of pathogenesis and pathophysiology is essential to establish effective strategy to treat the illness. Viral, host and environmental factors are involved in the development of SSPE. As host factors, immaturity of immune system and central nervous system are well recognized. Recently, we demonstrated that functional polymorphisms of MxA, interleukin(IL)-4 and interferon regulatory factor-1 (IRF-1) genes are associated with the development of SSPE in Japanese. High-density oligonucleotide microarray and subsequent quantitative reverse transcriptase-polymerase chain reaction demonstrated that the mRNA levels of granulysin were decreased in SSPE patients and were increased in measles patients, suggesting that granulysin might play a role in the host defense against MV and possibly be involved in the pathogenesis or pathophysiology of SSPE. In a Turkish study, association between angiotensin converting enzyme (ACE) gene polymorphism and SSPE was shown.
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PMID:[Host genetic factors for the development of SSPE]. 1769 85

Preclinical mouse models that recapitulate some characteristics of COVID-19 will facilitate focused study of pathogenesis and virus-host responses. Human angiotensin converting enzyme (hACE2) serves as an entry receptor for SARS-CoV-2 to infect people via binding to spike proteins. Herein we report development and characterization of a rapidly deployable COVID-19 mouse model. C57BL/6J (B6) mice expressing hACE2 in the lung were transduced by oropharyngeal delivery of the recombinant human adenovirus type 5 that expresses hACE2 (Ad5-hACE2). Mice were infected with SARS-CoV-2 at day 4 post-transduction and developed interstitial pneumonia associated with perivascular inflammation, accompanied by significantly higher viral load in lungs at days 3, 6, and 12 post-infection compared to Ad5-empty control group. SARS-CoV-2 was detected in pneumocytes in alveolar septa. Transcriptomic analysis of lungs demonstrated that the infected Ad5-hACE mice had a significant increase in interferon-dependent chemokines Cxcl9 and Cxcl10, and genes associated with effector T cell populations including Cd3g, Cd8a, and Gzmb. Pathway analysis showed that several KEGG pathways were enriched in the dataset, including cytokine-cytokine receptor interaction, the chemokine signaling pathway, the NOD-like receptor signaling pathway, the measles pathway, and the IL-17 signaling pathway. This response is correlative to clinical response in lungs of COVID-19 patients. These results demonstrate that expression of hACE2 via adenovirus delivery system sensitized the mouse to SARS-CoV-2 infection and resulted in the development of a mild COVID-19 phenotype, highlighting the immune and inflammatory host responses to SARS-CoV-2 infection. This rapidly deployable COVID-19 mouse model is useful for preclinical and pathogenesis studies of COVID-19. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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PMID:Lung Expression of Human ACE2 Sensitizes the Mouse to SARS-CoV-2 Infection. 3299 19