| Autor: |
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. |
| Abstrakt: |
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. |
