Generation of SARS-CoV-2 Mouse Model by Transient Expression of the Human ACE2 Gene Mediated by Intranasal Administration of AAV-hACE2

• Published in: Molecular biology (New York) Vol. 56; no. 5; pp. 705 - 712
• Main Authors: Glazkova, D. V., Bogoslovskaya, E. V., Urusov, F. A., Kartashova, N. P., Glubokova, E. A., Gracheva, A. V., Faizuloev, E. B., Trunova, G. V., Khokhlova, V. A., Bezborodova, O. A., Pankratov, A. A., Leneva, I. A., Shipulin, G. A.
• Format: Journal Article
• Language: English
• Published: Moscow Pleiades Publishing 2022; Springer Nature B.V
• Subjects: ACE2; ACE2 gene; Angiotensin; Angiotensin-converting enzyme 2; Animal models; Biochemistry; Biomedical and Life Sciences; Bronchopneumonia; Coronaviruses; Drug development; Human Genetics; Infections; Intranasal administration; Life Sciences; Peptidyl-dipeptidase A; Severe acute respiratory syndrome coronavirus 2; Virial Infections: and Pathogenesis Mechanisms to Therapy; Virial Infections: Replication and Pathogenesis Mechanisms to Therapy; BALB/c mice; SARS-CoV-2; AAV-DJ; AAV9; AAV6; hACE2
• ISSN: 0026-8933; 1608-3245
• DOI: 10.1134/S0026893322050065

One of the most important steps in the development of drugs and vaccines against a new coronavirus infection is their testing on a relevant animal model. The laboratory mouse, with well-studied immunology, is the preferred mammalian model in experimental medicine. However, mice are not susceptible to infection with SARS-CoV-2 due to the lack of human angiotensin-converting enzyme (hACE2), which is the cell receptor of SARS-CoV-2 and necessary for the entry of the virus into the cell. In present work, it was shown that intranasal administration of the adeno-associated vectors AAV9 and AAV-DJ encoding the hACE2 provided a high level of expression of
ACE2
gene in the lungs of mice. In contrast, the introduction of the AAV6 vector led to a low level
ACE2
expression. Infection with SARS-CoV-2 of mice expressing hACE2 in the lungs led to virus replication and development of bronchopneumonia on the 7th day after infection. Thus, a simple method for delivering the human
ACE2
gene to mouse lungs by intranasal administration of the AAV vector has been proposed. This approach enabled rapid generation of mouse model for studying coronavirus infection.