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Mice with induced pulmonary morbidities display severe lung inflammation and mortality following exposure to SARS-CoV-2.
Falach, Reut; Bar-On, Liat; Lazar, Shlomi; Kadar, Tamar; Mazor, Ohad; Aftalion, Moshe; Gur, David; Evgy, Yentl; Shifman, Ohad; Aminov, Tamar; Israeli, Ofir; Cohen-Gihon, Inbar; Zaide, Galia; Gutman, Hila; Vagima, Yaron; Makdasi, Efi; Stein, Dana; Rosenfeld, Ronit; Alcalay, Ron; Zahavy, Eran; Levy, Haim; Glinert, Itai; Ben-Shmuel, Amir; Israely, Tomer; Melamed, Sharon; Politi, Boaz; Achdout, Hagit; Yitzhaki, Shmuel; Kronman, Chanoch; Sabo, Tamar.
  • Falach R; Department of Biochemistry and Molecular Genetics.
  • Bar-On L; Department of Biochemistry and Molecular Genetics.
  • Lazar S; Department of Pharmacology, and.
  • Kadar T; Department of Pharmacology, and.
  • Mazor O; Department of Infectious Diseases, Israel Institute for Biological Research, Ness-Ziona, Israel.
  • Aftalion M; Department of Biochemistry and Molecular Genetics.
  • Gur D; Department of Biochemistry and Molecular Genetics.
  • Evgy Y; Department of Biochemistry and Molecular Genetics.
  • Shifman O; Department of Biochemistry and Molecular Genetics.
  • Aminov T; Department of Biochemistry and Molecular Genetics.
  • Israeli O; Department of Biochemistry and Molecular Genetics.
  • Cohen-Gihon I; Department of Biochemistry and Molecular Genetics.
  • Zaide G; Department of Biochemistry and Molecular Genetics.
  • Gutman H; Department of Pharmacology, and.
  • Vagima Y; Department of Biochemistry and Molecular Genetics.
  • Makdasi E; Department of Infectious Diseases, Israel Institute for Biological Research, Ness-Ziona, Israel.
  • Stein D; Department of Biochemistry and Molecular Genetics.
  • Rosenfeld R; Department of Biochemistry and Molecular Genetics.
  • Alcalay R; Department of Biochemistry and Molecular Genetics.
  • Zahavy E; Department of Biochemistry and Molecular Genetics.
  • Levy H; Department of Infectious Diseases, Israel Institute for Biological Research, Ness-Ziona, Israel.
  • Glinert I; Department of Infectious Diseases, Israel Institute for Biological Research, Ness-Ziona, Israel.
  • Ben-Shmuel A; Department of Infectious Diseases, Israel Institute for Biological Research, Ness-Ziona, Israel.
  • Israely T; Department of Infectious Diseases, Israel Institute for Biological Research, Ness-Ziona, Israel.
  • Melamed S; Department of Infectious Diseases, Israel Institute for Biological Research, Ness-Ziona, Israel.
  • Politi B; Department of Infectious Diseases, Israel Institute for Biological Research, Ness-Ziona, Israel.
  • Achdout H; Department of Infectious Diseases, Israel Institute for Biological Research, Ness-Ziona, Israel.
  • Yitzhaki S; Department of Infectious Diseases, Israel Institute for Biological Research, Ness-Ziona, Israel.
  • Kronman C; Department of Biochemistry and Molecular Genetics.
  • Sabo T; Department of Biochemistry and Molecular Genetics.
JCI Insight ; 6(12)2021 06 22.
Article in English | MEDLINE | ID: covidwho-1223641
Semantic information from SemMedBD (by NLM)
1. Lung LOCATION_OF Severe inflammation
Subject
Lung
Predicate
LOCATION_OF
Object
Severe inflammation
2. bleomycin CAUSES Severe disease
Subject
bleomycin
Predicate
CAUSES
Object
Severe disease
3. Ricin CAUSES Severe disease
Subject
Ricin
Predicate
CAUSES
Object
Severe disease
4. COVID-19 PROCESS_OF Mus
Subject
COVID-19
Predicate
PROCESS_OF
Object
Mus
5. Heart LOCATION_OF High Level
Subject
Heart
Predicate
LOCATION_OF
Object
High Level
6. Lung LOCATION_OF High Level
Subject
Lung
Predicate
LOCATION_OF
Object
High Level
7. RNA Recognition Motif PART_OF 2019 novel coronavirus
Subject
RNA Recognition Motif
Predicate
PART_OF
Object
2019 novel coronavirus
8. Monoclonal Antibodies PRODUCES RNA Recognition Motif
Subject
Monoclonal Antibodies
Predicate
PRODUCES
Object
RNA Recognition Motif
9. Monoclonal Antibodies AFFECTS COVID-19
Subject
Monoclonal Antibodies
Predicate
AFFECTS
Object
COVID-19
10. Virus Internalization PROCESS_OF Mus
Subject
Virus Internalization
Predicate
PROCESS_OF
Object
Mus
11. ACE2 gene|ACE2 AFFECTS Uptake
Subject
ACE2 gene|ACE2
Predicate
AFFECTS
Object
Uptake
12. Exacerbation PROCESS_OF Patients
Subject
Exacerbation
Predicate
PROCESS_OF
Object
Patients
13. Lung LOCATION_OF Severe inflammation
Subject
Lung
Predicate
LOCATION_OF
Object
Severe inflammation
14. bleomycin CAUSES Severe disease
Subject
bleomycin
Predicate
CAUSES
Object
Severe disease
15. Ricin CAUSES Severe disease
Subject
Ricin
Predicate
CAUSES
Object
Severe disease
16. COVID-19 PROCESS_OF Mus
Subject
COVID-19
Predicate
PROCESS_OF
Object
Mus
17. Heart LOCATION_OF High Level
Subject
Heart
Predicate
LOCATION_OF
Object
High Level
18. Lung LOCATION_OF High Level
Subject
Lung
Predicate
LOCATION_OF
Object
High Level
19. RNA Recognition Motif PART_OF 2019 novel coronavirus
Subject
RNA Recognition Motif
Predicate
PART_OF
Object
2019 novel coronavirus
20. Monoclonal Antibodies PRODUCES RNA Recognition Motif
Subject
Monoclonal Antibodies
Predicate
PRODUCES
Object
RNA Recognition Motif
21. Monoclonal Antibodies AFFECTS COVID-19
Subject
Monoclonal Antibodies
Predicate
AFFECTS
Object
COVID-19
22. Virus Internalization PROCESS_OF Mus
Subject
Virus Internalization
Predicate
PROCESS_OF
Object
Mus
23. ACE2 gene|ACE2 AFFECTS Uptake
Subject
ACE2 gene|ACE2
Predicate
AFFECTS
Object
Uptake
24. Exacerbation PROCESS_OF Patients
Subject
Exacerbation
Predicate
PROCESS_OF
Object
Patients
ABSTRACT
Mice are normally unaffected by SARS coronavirus 2 (SARS-CoV-2) infection since the virus does not bind effectively to the murine version of the angiotensin-converting enzyme 2 (ACE2) receptor molecule. Here, we report that induced mild pulmonary morbidities rendered SARS-CoV-2-refractive CD-1 mice susceptible to this virus. Specifically, SARS-CoV-2 infection after application of low doses of the acute lung injury stimulants bleomycin or ricin caused severe disease in CD-1 mice, manifested by sustained body weight loss and mortality rates greater than 50%. Further studies revealed markedly higher levels of viral RNA in the lungs, heart, and serum of low-dose ricin-pretreated mice compared with non-pretreated mice. Furthermore, lung extracts prepared 2-3 days after viral infection contained subgenomic mRNA and virus particles capable of replication only when derived from the pretreated mice. The deleterious effects of SARS-CoV-2 infection were effectively alleviated by passive transfer of polyclonal or monoclonal antibodies generated against the SARS-CoV-2 receptor binding domain (RBD). Thus, viral cell entry in the sensitized mice seems to depend on viral RBD binding, albeit by a mechanism other than the canonical ACE2-mediated uptake route. This unique mode of viral entry, observed over a mildly injured tissue background, may contribute to the exacerbation of coronavirus disease 2019 (COVID-19) pathologies in patients with preexisting morbidities.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Ricin / Bleomycin / Lung Injury / COVID-19 Limits: Animals Language: English Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Ricin / Bleomycin / Lung Injury / COVID-19 Limits: Animals Language: English Year: 2021 Document Type: Article