Molecular Cloning, mRNA Expression and Chromosomal Localization of Mouse Angiotensin-converting Enzyme-related Carboxypeptidase (mACE2)

Komatsu, Takami; Suzuki, Yutaka; Imai, Jun‐ichi; Sugano, Sumio; Hida, Munetomo; Tanigami, Akira; Muroi, Sawako; Yamada, Yosuke; Hanaoka, Kazuo

doi:10.1080/1042517021000021608

Cited by 74 publications

(75 citation statements)

References 11 publications

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“…Northern blotting showed that ACE2 mRNA is expressed abundantly in endothelial cells of the heart, kidneys, and testis (37). In addition, RT-PCR and immunocytochemistry showed that ACE2 mRNA and protein are expressed on oral, nasal, and intestinal mucosa, alveolar epithelial cells in lung, stomach, skin, lymph nodes, thymus, bone marrow, spleen liver, kidney, and brain, and arterial and venous endothelial cells and arterial smooth muscle cells in many organs (38)(39)(40)(41). These sites for ACE2 expression include most of the sites for SARS-CoV replication in autopsy specimens (26).…”

Section: Discussionmentioning

confidence: 99%

CD209L (L-SIGN) is a receptor for severe acute respiratory syndrome coronavirus

Jeffers

Tusell

Gillim-Ross

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

580

570

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Severe acute respiratory syndrome (SARS) is caused by a novel coronavirus called SARS-CoV (1-3). The virus causes atypical pneumonia with diffuse alveolar damage with an overall mortality of Ϸ10% that ranges from 0% in children and 50% in persons over 65 (2). Coronaviruses bind to their glycoprotein receptors by the Ϸ200-kDa spike glycoprotein, S, on the viral envelope. Identification of virus receptors can provide insight into mechanisms of virus entry, tissue tropism, pathogenesis, and host range.Several types of receptors were previously identified for coronavirus S glycoproteins. The receptors for the murine coronavirus mouse hepatitis virus are murine carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) and related murine glycoproteins in the carcinoembryonic antigen family in the Ig superfamily (4). The receptors for human coronavirus 229E (HCoV-229E), transmissible gastroenteritis virus of swine, and feline coronavirus in genetic group 1 are aminopeptidase N (APN) glycoproteins (5-8).Angiotensin-converting enzyme 2 (ACE2) was found to be an efficient receptor for the S glycoprotein of SARS-CoV (9, 10). Because the Vero line of rhesus monkey kidney cells is highly susceptible to infection with SARS-CoV, Li et al. (9) used a codon-optimized soluble SARS-CoV spike glycoprotein (amino acids 12-672) fused to the Fc domain of human IgG1 to immunoprecipitate a putative receptor glycoprotein from Vero cell membranes and identified the simian ACE2 protein by mass spectrometry. They showed that expression of recombinant human ACE2 greatly enhanced the susceptibility of human 293T cells to infection by SARS-CoV. Wang et al. (10) independently demonstrated that human ACE2 is a receptor for SARS-CoV by transducing HeLa cells with a retrovirus library of cDNAs from Vero E6 cells and by using flow cytometry to select transduced cells that bound to purified soluble SARS-CoV S glycoprotein (amino acids 14-502) with a 6-histidine tag. They found that the simian cDNA in these cells, which encoded triosephosphate isomerase, enhanced expression of human ACE2 by inserting into the HeLa cell genome immediately upstream of the ACE2 ORF. Murine NIH 3T3 cells expressing recombinant human ACE2, but not those expressing recombinant triosephosphate isomerase, were susceptible to infection by HIV pseudovirus expressing SARS-CoV S protein.In this report, we describe the discovery of an additional receptor for SARS-CoV, CD209L (also called L-SIGN, DC-SIGNR, and DC-SIGN2) (11). Our strategy for identifying a SARS-CoV receptor was to transduce a human lung cDNA library carried by a retroviral vector into Chinese hamster ovary (CHO) cells and use flow cytometry to select transduced CHO cells that bound soluble, codon-optimized, c-myc-tagged SARSCoV S 590 glycoprotein (amino acids 1-590) expressed in 293T cells. The SARS-CoV S 590 -binding cells were then challenged with infectious SARS-CoV, and infection was demonstrated by detection of subgenomic viral RNA synthesis and immunofluorescence with antiviral antibody. The finding that ...

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Section: Discussionmentioning

confidence: 99%

CD209L (L-SIGN) is a receptor for severe acute respiratory syndrome coronavirus

Jeffers

Tusell

Gillim-Ross

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

580

570

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“…Murine ACE2 cDNA was cloned in lentiviral vector (lenti-ACE2) essentially as described elsewhere, 18,19 and production and titration of lentiviral particles were carried out as described previously. 20,21 Lentiviral vector containing no insert was used as control, whereas a vector containing placental alkaline phosphatase reporter gene was used to characterize in vivo transduction efficiency.…”

Section: Characterization Of Ace2 In Lentiviral Vectormentioning

confidence: 99%

Cardiac Overexpression of Angiotensin Converting Enzyme 2 Protects the Heart From Ischemia-Induced Pathophysiology

et al. 2008

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Abstract-Angiotensin converting enzyme 2 (ACE2) has been linked to cardiac dysfunction and hypertension-induced cardiac pathophysiology. In this study, we used a gene overexpression approach to investigate the role of ACE2 in cardiac function and remodeling after myocardial infarction. Rats received an intracardiac injection of 4.5ϫ10 8 lentivirus containing ACE2 cDNA, followed by permanent coronary artery ligation (CAL) of the left anterior descending artery. At 24 hours and 6 weeks after surgery, cardiac functions, viability, and pathophysiology were assessed by MRI) and by histological analysis. At 24 hours post-CAL, left ventricular (LV) anterior wall motion was stunted to the same extent in control CAL and lenti-ACE2-treated CAL rats. However lenti-ACE2-treated CAL rats showed a 60% reduction in delayed contrast-enhanced LV volume after gadodiamide injection, indicating early ischemic protection of myocardium by ACE2. At 6 weeks after CAL, lenti-ACE2 rats demonstrated a complete rescue of cardiac output, a 41% rescue of ejection fraction, a 44% rescue in contractility, a 37% rescue in motion, and a 53% rescue in LV anterior (infracted) wall thinning compared with control CAL rats. No changes were observed in the LV posterior (noninfarcted) wall other than an 81% rescue in motion produced by ACE2 in CAL rats. Finally, infarct size measured by 2,3,5-triphenyl-tetrazolium chloride staining was not significantly different between the ligated groups. These observations demonstrate that cardiac overexpression of ACE2 exerts protective influence on the heart during myocardial infarction by preserving cardiac functions, LV wall motion and contractility, and by attenuating LV wall thinning. (Hypertension. 2008;51:712-718.)

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“…The role of a recently identified receptor for SARS CoV, angiotensin-converting enzyme 2 (15), as a determinant of the host range of SARS CoV remains to be determined. The presence of angiotensin-converting enzyme 2 homologs in a wide range of species (4,12) may account for the broad host range of SARS CoV.…”

mentioning

confidence: 99%

Severe Acute Respiratory Syndrome Coronavirus Infection of Golden Syrian Hamsters

Roberts

Vogel

Guarner

et al. 2005

J Virol

275

306

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Small animal models are needed in order to evaluate the efficacy of candidate vaccines and antivirals directed against the severe acute respiratory syndrome coronavirus (SARS CoV). We investigated the ability of SARS CoV to infect 5-week-old Golden Syrian hamsters. When administered intranasally, SARS CoV replicates to high titers in the lungs and nasal turbinates. Peak replication in the lower respiratory tract was noted on day 2 postinfection (p.i.) and was cleared by day 7 p.i. Low levels of virus were present in the nasal turbinates of a few hamsters at 14 days p.i. Viral replication in epithelial cells of the respiratory tract was accompanied by cellular necrosis early in infection, followed by an inflammatory response coincident with viral clearance, focal consolidation in pulmonary tissue, and eventual pulmonary tissue repair. Despite high levels of virus replication and associated pathology in the respiratory tract, the hamsters showed no evidence of disease. Neutralizing antibodies were detected in sera at day 7 p.i., and mean titers at day 28 p.i. exceeded 1:400. Hamsters challenged with SARS CoV at day 28 p.i. were completely protected from virus replication and accompanying pathology in the respiratory tract. Comparing these data to the mouse model, SARS CoV replicates to a higher titer and for a longer duration in the respiratory tract of hamsters and is accompanied by significant pathology that is absent in mice. Viremia and extrapulmonary spread of SARS CoV to liver and spleen, which are seen in hamsters, were not detected in mice. The hamster, therefore, is superior to the mouse as a model for the evaluation of antiviral agents and candidate vaccines against SARS CoV replication.

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Molecular Cloning, mRNA Expression and Chromosomal Localization of Mouse Angiotensin-converting Enzyme-related Carboxypeptidase (mACE2)

Cited by 74 publications

References 11 publications

CD209L (L-SIGN) is a receptor for severe acute respiratory syndrome coronavirus

CD209L (L-SIGN) is a receptor for severe acute respiratory syndrome coronavirus

Cardiac Overexpression of Angiotensin Converting Enzyme 2 Protects the Heart From Ischemia-Induced Pathophysiology

Severe Acute Respiratory Syndrome Coronavirus Infection of Golden Syrian Hamsters

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