Biomaterial Database

Mice humanized for MHC and hACE2 with high permissiveness to SARS-CoV-2 omicron replication. 2023

Fabien Le Chevalier, and Pierre Authié, and Sébastien Chardenoux, and Maryline Bourgine, and Benjamin Vesin, and Delphine Cussigh, and Yohann Sassier, and Ingrid Fert, and Amandine Noirat, and Kirill Nemirov, and François Anna, and Marion Bérard, and Françoise Guinet, and David Hardy, and Pierre Charneau, and François Lemonnier, and Francina Langa-Vives, and Laleh Majlessi

Pasteur-TheraVectys Joint Lab, Institut Pasteur, Université Paris Cité, Virology Department, 75724 Paris, France. Electronic address: fabien.le-chevalier@pasteur.fr.

Human Angiotensin-Converting Enzyme 2 (hACE2) is the major receptor enabling host cell invasion by SARS-CoV-2 via interaction with Spike. The murine ACE2 does not interact efficiently with SARS-CoV-2 Spike and therefore the laboratory mouse strains are not permissive to SARS-CoV-2 replication. Here, we generated new hACE2 transgenic mice, which harbor the hACE2 gene under the human keratin 18 promoter, in "HHD-DR1" background. HHD-DR1 mice are fully devoid of murine Major Histocompatibility Complex (MHC) molecules of class-I and -II and express only MHC molecules from Human Leukocyte Antigen (HLA) HLA 02.01, DRA01.01, DRB1.01.01 alleles, widely expressed in human populations. We selected three transgenic strains, with various hACE2 mRNA expression levels and distinctive profiles of lung and/or brain permissiveness to SARS-CoV-2 replication. These new hACE2 transgenic strains display high permissiveness to the replication of SARS-CoV-2 Omicron sub-variants, while the previously available B6.K18-ACE22Prlmn/JAX mice have been reported to be poorly susceptible to infection with Omicron. As a first application, one of these MHC- and ACE2-humanized strains was successfully used to show the efficacy of a lentiviral-based COVID-19 vaccine.

UI	MeSH Term	Description	Entries
D008285	Major Histocompatibility Complex	The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) TRANSPLANTATION ANTIGENS, genes which control the structure of the IMMUNE RESPONSE-ASSOCIATED ANTIGENS, HUMAN; the IMMUNE RESPONSE GENES which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement.	Histocompatibility Complex,Complex, Histocompatibility,Complex, Major Histocompatibility,Complices, Histocompatibility,Complices, Major Histocompatibility,Histocompatibility Complex, Major,Histocompatibility Complices,Histocompatibility Complices, Major,Major Histocompatibility Complices
D008822	Mice, Transgenic	Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.	Transgenic Mice,Founder Mice, Transgenic,Mouse, Founder, Transgenic,Mouse, Transgenic,Mice, Transgenic Founder,Transgenic Founder Mice,Transgenic Mouse
D010541	Permissiveness	The attitude that grants freedom of expression and activity to another individual, but not necessarily with sanction or approval.	Permissivenesses
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000085962	Angiotensin-Converting Enzyme 2	A transmembrane glycoprotein with an extracellular catalytic domain which functions as a carboxypeptidase. It cleaves a single C-terminal residue from a distinct range of substrates. The catalytic efficiency is 400-fold higher with ANGIOTENSIN II as a substrate than with ANGIOTENSIN I. Angiotensin-converting enzyme 2 is also is a functional receptor for the spike glycoprotein (SPIKE PROTEIN, CORONAVIRUS) of the CORONAVIRUSES SARS-COV, SARS-COV2, and HCOV-NL63.	ACE-Related Carboxypeptidase,ACE2 Angiotensin-Converting Enzyme Protein 2,ACE2 Enzyme,ACE2 Protein,Angiotensin Converting Enzyme 2,Angiotensin-Converting Enzyme-Related Carboxypeptidase,ACE Related Carboxypeptidase,ACE2 Angiotensin Converting Enzyme Protein 2,Angiotensin Converting Enzyme Related Carboxypeptidase,Carboxypeptidase, ACE-Related,Carboxypeptidase, Angiotensin-Converting Enzyme-Related
D000086382	COVID-19	A viral disorder generally characterized by high FEVER; COUGH; DYSPNEA; CHILLS; PERSISTENT TREMOR; MUSCLE PAIN; HEADACHE; SORE THROAT; a new loss of taste and/or smell (see AGEUSIA and ANOSMIA) and other symptoms of a VIRAL PNEUMONIA. In severe cases, a myriad of coagulopathy associated symptoms often correlating with COVID-19 severity is seen (e.g., BLOOD COAGULATION; THROMBOSIS; ACUTE RESPIRATORY DISTRESS SYNDROME; SEIZURES; HEART ATTACK; STROKE; multiple CEREBRAL INFARCTIONS; KIDNEY FAILURE; catastrophic ANTIPHOSPHOLIPID ANTIBODY SYNDROME and/or DISSEMINATED INTRAVASCULAR COAGULATION). In younger patients, rare inflammatory syndromes are sometimes associated with COVID-19 (e.g., atypical KAWASAKI SYNDROME; TOXIC SHOCK SYNDROME; pediatric multisystem inflammatory disease; and CYTOKINE STORM SYNDROME). A coronavirus, SARS-CoV-2, in the genus BETACORONAVIRUS is the causative agent.	2019 Novel Coronavirus Disease,2019 Novel Coronavirus Infection,2019-nCoV Disease,2019-nCoV Infection,COVID-19 Pandemic,COVID-19 Pandemics,COVID-19 Virus Disease,COVID-19 Virus Infection,Coronavirus Disease 2019,Coronavirus Disease-19,SARS Coronavirus 2 Infection,SARS-CoV-2 Infection,Severe Acute Respiratory Syndrome Coronavirus 2 Infection,COVID19,2019 nCoV Disease,2019 nCoV Infection,2019-nCoV Diseases,2019-nCoV Infections,COVID 19,COVID 19 Pandemic,COVID 19 Virus Disease,COVID 19 Virus Infection,COVID-19 Virus Diseases,COVID-19 Virus Infections,Coronavirus Disease 19,Disease 2019, Coronavirus,Disease, 2019-nCoV,Disease, COVID-19 Virus,Infection, 2019-nCoV,Infection, COVID-19 Virus,Infection, SARS-CoV-2,Pandemic, COVID-19,SARS CoV 2 Infection,SARS-CoV-2 Infections,Virus Disease, COVID-19,Virus Infection, COVID-19
D000086402	SARS-CoV-2	A species of BETACORONAVIRUS causing atypical respiratory disease (COVID-19) in humans. The organism was first identified in 2019 in Wuhan, China. The natural host is the Chinese intermediate horseshoe bat, RHINOLOPHUS affinis.	2019 Novel Coronavirus,COVID-19 Virus,COVID19 Virus,Coronavirus Disease 2019 Virus,SARS Coronavirus 2,SARS-CoV-2 Virus,Severe Acute Respiratory Syndrome Coronavirus 2,Wuhan Coronavirus,Wuhan Seafood Market Pneumonia Virus,2019-nCoV,2019 Novel Coronaviruses,COVID 19 Virus,COVID-19 Viruses,COVID19 Viruses,Coronavirus 2, SARS,Coronavirus, 2019 Novel,Coronavirus, Wuhan,Novel Coronavirus, 2019,SARS CoV 2 Virus,SARS-CoV-2 Viruses,Virus, COVID-19,Virus, COVID19,Virus, SARS-CoV-2,Viruses, COVID19
D000086663	COVID-19 Vaccines	Vaccines or candidate vaccines containing SARS-CoV-2 component antigens, genetic materials, or inactivated SARS-CoV-2 virus, and designed to prevent COVID-19.	2019 Novel Coronavirus Vaccine,2019 Novel Coronavirus Vaccines,2019-nCoV Vaccine,2019-nCoV Vaccines,COVID 19 Vaccine,COVID-19 Vaccine,COVID-19 Virus Vaccine,COVID-19 Virus Vaccines,COVID19 Vaccine,COVID19 Vaccines,COVID19 Virus Vaccine,COVID19 Virus Vaccines,Coronavirus Disease 2019 Vaccine,Coronavirus Disease 2019 Vaccines,Coronavirus Disease 2019 Virus Vaccine,Coronavirus Disease 2019 Virus Vaccines,Coronavirus Disease-19 Vaccine,Coronavirus Disease-19 Vaccines,SARS Coronavirus 2 Vaccines,SARS-CoV-2 Vaccine,SARS-CoV-2 Vaccines,SARS2 Vaccine,SARS2 Vaccines,2019 nCoV Vaccine,2019 nCoV Vaccines,COVID 19 Vaccines,COVID 19 Virus Vaccine,COVID 19 Virus Vaccines,Coronavirus Disease 19 Vaccine,Coronavirus Disease 19 Vaccines,SARS CoV 2 Vaccine,SARS CoV 2 Vaccines,Vaccine, 2019-nCoV,Vaccine, COVID 19,Vaccine, COVID-19,Vaccine, COVID-19 Virus,Vaccine, COVID19,Vaccine, COVID19 Virus,Vaccine, Coronavirus Disease-19,Vaccine, SARS-CoV-2,Vaccine, SARS2,Vaccines, 2019-nCoV,Vaccines, COVID-19,Vaccines, COVID-19 Virus,Vaccines, COVID19,Vaccines, COVID19 Virus,Vaccines, Coronavirus Disease-19,Vaccines, SARS-CoV-2,Vaccines, SARS2,Virus Vaccine, COVID-19,Virus Vaccine, COVID19,Virus Vaccines, COVID-19,Virus Vaccines, COVID19
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus