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SARS-CoV-2 Variant-Specific Infectivity and Immune Profiles Are Detectable in a Humanized Lung Mouse Model.
Di, Yunyun; Lew, Jocelyne; Goncin, Una; Radomska, Anna; Rout, Saurav S; Gray, Bridget E T; Machtaler, Steven; Falzarano, Darryl; Lavender, Kerry J.
  • Di Y; Department of Biochemistry, Microbiology and Immunology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada.
  • Lew J; Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, SK S7N 5E3, Canada.
  • Goncin U; Department of Medical Imaging, University of Saskatchewan, Saskatoon, SK S7N 0W8, Canada.
  • Radomska A; Department of Pathology and Laboratory Medicine, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada.
  • Rout SS; Department of Biochemistry, Microbiology and Immunology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada.
  • Gray BET; Animal Care and Research Support, Research Excellence and Innovation, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada.
  • Machtaler S; Department of Medical Imaging, University of Saskatchewan, Saskatoon, SK S7N 0W8, Canada.
  • Falzarano D; Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, SK S7N 5E3, Canada.
  • Lavender KJ; Department of Veterinary Microbiology, University of Saskatchewan, Saskatoon, SK S7N 5B4, Canada.
Viruses ; 14(10)2022 10 16.
Статья в английский | MEDLINE | ID: covidwho-2071843
ABSTRACT
Small animal models that accurately model pathogenesis of SARS-CoV-2 variants are required for ongoing research efforts. We modified our human immune system mouse model to support replication of SARS-CoV-2 by implantation of human lung tissue into the mice to create TKO-BLT-Lung (L) mice and compared infection with two different variants in a humanized lung model. Infection of TKO-BLT-L mice with SARS-CoV-2 recapitulated the higher infectivity of the B.1.1.7 variant with more animals becoming infected and higher sustained viral loads compared to mice challenged with an early B lineage (614D) virus. Viral lesions were observed in lung organoids but no differences were detected between the viral variants as expected. Partially overlapping but distinct immune profiles were also observed between the variants with a greater Th1 profile in VIDO-01 and greater Th2 profile in B.1.1.7 infection. Overall, the TKO-BLT-L mouse supported SARS-CoV-2 infection, recapitulated key known similarities and differences in infectivity and pathogenesis as well as revealing previously unreported differences in immune responses between the two viral variants. Thus, the TKO-BLT-L model may serve as a useful animal model to study the immunopathobiology of newly emerging variants in the context of genuine human lung tissue and immune cells.
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Полный текст: Имеется в наличии Коллекция: Международные базы данных база данных: MEDLINE Основная тема: SARS-CoV-2 / COVID-19 Темы: Варианты Пределы темы: Животные / Люди Язык: английский Год: 2022 Тип: Статья Аффилированная страна: V14102272

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Полный текст: Имеется в наличии Коллекция: Международные базы данных база данных: MEDLINE Основная тема: SARS-CoV-2 / COVID-19 Темы: Варианты Пределы темы: Животные / Люди Язык: английский Год: 2022 Тип: Статья Аффилированная страна: V14102272