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SARS-CoV-2 Infects Primary Neurons from Human ACE2 Expressing Mice and Upregulates Genes Involved in the Inflammatory and Necroptotic Pathways.
Rothan, Hussin A; Kumari, Pratima; Stone, Shannon; Natekar, Janhavi P; Arora, Komal; Auroni, Tabassum T; Kumar, Mukesh.
  • Rothan HA; Department of Biology, College of Arts and Sciences, Georgia State University, Atlanta, GA 30303, USA.
  • Kumari P; Department of Biology, College of Arts and Sciences, Georgia State University, Atlanta, GA 30303, USA.
  • Stone S; Department of Biology, College of Arts and Sciences, Georgia State University, Atlanta, GA 30303, USA.
  • Natekar JP; Department of Biology, College of Arts and Sciences, Georgia State University, Atlanta, GA 30303, USA.
  • Arora K; Department of Biology, College of Arts and Sciences, Georgia State University, Atlanta, GA 30303, USA.
  • Auroni TT; Department of Biology, College of Arts and Sciences, Georgia State University, Atlanta, GA 30303, USA.
  • Kumar M; Department of Biology, College of Arts and Sciences, Georgia State University, Atlanta, GA 30303, USA.
Pathogens ; 11(2)2022 Feb 17.
Статья в английский | MEDLINE | ID: covidwho-1701716
ABSTRACT
Transgenic mice expressing human angiotensin-converting enzyme 2 under the cytokeratin 18 promoter (K18-hACE2) have been extensively used to investigate the pathogenesis and tissue tropism of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Neuroinvasion and the replication of SARS-CoV-2 within the central nervous system (CNS) of K18-hACE2 mice is associated with increased mortality; although, the mechanisms by which this occurs remain unclear. In this study, we generated primary neuronal cultures from K18-hACE2 mice to investigate the effects of a SARS-CoV-2 infection. We also evaluated the immunological response to SARS-CoV-2 infection in the CNS of K18-hACE2 mice and mouse neuronal cultures. Our data show that neuronal cultures obtained from K18-hACE2 mice are permissive to SARS-CoV-2 infection and support productive virus replication. Furthermore, SARS-CoV-2 infection upregulated the expression of genes involved in innate immunity and inflammation, including IFN-α, ISG-15, CXCL10, CCL2, IL-6 and TNF-α, in the neurons and mouse brains. In addition, we found that SARS-CoV-2 infection of neurons and mouse brains activates the ZBP1/pMLKL-regulated necroptosis pathway. Together, our data provide insights into the neuropathogenesis of SARS-CoV-2 infection in K18-hACE2 mice.
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Полный текст: Имеется в наличии Коллекция: Международные базы данных база данных: MEDLINE Тип исследования: Экспериментальные исследования Язык: английский Год: 2022 Тип: Статья Аффилированная страна: Pathogens11020257

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Полный текст: Имеется в наличии Коллекция: Международные базы данных база данных: MEDLINE Тип исследования: Экспериментальные исследования Язык: английский Год: 2022 Тип: Статья Аффилированная страна: Pathogens11020257