tetano
Editor, Senior Moderator
Pathogens
. 2022 Feb 17;11(2):257.
doi: 10.3390/pathogens11020257.
SARS-CoV-2 Infects Primary Neurons from Human ACE2 Expressing Mice and Upregulates Genes Involved in the Inflammatory and Necroptotic Pathways
Hussin A Rothan[SUP] 1 [/SUP], Pratima Kumari[SUP] 1 [/SUP], Shannon Stone[SUP] 1 [/SUP], Janhavi P Natekar[SUP] 1 [/SUP], Komal Arora[SUP] 1 [/SUP], Tabassum T Auroni[SUP] 1 [/SUP], Mukesh Kumar[SUP] 1 [/SUP]
Affiliations
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.
Keywords: COVID-19; K18-hACE2 mice; SARS-CoV-2; inflammation; necroptosis; neurons; neuropathogenesis.
. 2022 Feb 17;11(2):257.
doi: 10.3390/pathogens11020257.
SARS-CoV-2 Infects Primary Neurons from Human ACE2 Expressing Mice and Upregulates Genes Involved in the Inflammatory and Necroptotic Pathways
Hussin A Rothan[SUP] 1 [/SUP], Pratima Kumari[SUP] 1 [/SUP], Shannon Stone[SUP] 1 [/SUP], Janhavi P Natekar[SUP] 1 [/SUP], Komal Arora[SUP] 1 [/SUP], Tabassum T Auroni[SUP] 1 [/SUP], Mukesh Kumar[SUP] 1 [/SUP]
Affiliations
- PMID: 35215199
- DOI: 10.3390/pathogens11020257
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.
Keywords: COVID-19; K18-hACE2 mice; SARS-CoV-2; inflammation; necroptosis; neurons; neuropathogenesis.