Chronological brain lesions after SARS-CoV-2 infection in hACE2-transgenic mice
Por:
Vidal, E, Lopez-Figueroa, C, Rodon, J, Perez, M, Brustolin, M, Cantero, G, Guallar, V, Izquierdo-Useros, N, Carrillo, J, Blanco, J, Clotet, B, Vergara-Alert, J and Segales, J
Publicada:
1 jul 2022
Ahead of Print:
1 dic 2021
Resumen:
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes respiratory disease, but it can also affect other organs including the central nervous system. Several animal models have been developed to address different key questions related to Coronavirus Disease 2019 (COVID-19). Wild-type mice are minimally susceptible to certain SARS-CoV-2 lineages (beta and gamma variants), whereas hACE2-transgenic mice succumb to SARS-CoV-2 and develop a fatal neurological disease. In this article, we aimed to chronologically characterize SARS-CoV-2 neuroinvasion and neuropathology. Necropsies were performed at different time points, and the brain and olfactory mucosa were processed for histopathological analysis. SARS-CoV-2 virological assays including immunohistochemistry were performed along with a panel of antibodies to assess neuroinflammation. At 6 to 7 days post inoculation (dpi), brain lesions were characterized by nonsuppurative meningoencephalitis and diffuse astrogliosis and microgliosis. Vasculitis and thrombosis were also present and associated with occasional microhemorrhages and spongiosis. Moreover, there was vacuolar degeneration of virus-infected neurons. At 2 dpi, SARS-CoV-2 immunolabeling was only found in the olfactory mucosa, but at 4 dpi intraneuronal virus immunolabeling had already reached most of the brain areas. Maximal distribution of the virus was observed throughout the brain at 6 to 7 dpi except for the cerebellum, which was mostly spared. Our results suggest an early entry of the virus through the olfactory mucosa and a rapid interneuronal spread of the virus leading to acute encephalitis and neuronal damage in this mouse model.
Filiaciones:
Vidal, E:
UAB, Ctr Recerca Sanitat Anim CReSA, IRTA, Campus UAB, Barcelona 08193, Catalonia, Spain
Lopez-Figueroa, C:
UAB, Ctr Recerca Sanitat Anim CReSA, IRTA, Campus UAB, Barcelona 08193, Catalonia, Spain
Rodon, J:
UAB, Ctr Recerca Sanitat Anim CReSA, IRTA, Campus UAB, Barcelona 08193, Catalonia, Spain
Perez, M:
UAB, Ctr Recerca Sanitat Anim CReSA, IRTA, Campus UAB, Barcelona 08193, Catalonia, Spain
Brustolin, M:
UAB, Ctr Recerca Sanitat Anim CReSA, IRTA, Campus UAB, Barcelona 08193, Catalonia, Spain
Cantero, G:
UAB, Ctr Recerca Sanitat Anim CReSA, IRTA, Campus UAB, Barcelona 08193, Catalonia, Spain
Guallar, V:
Barcelona Supercomp Ctr BSC, Barcelona, Spain
Catalan Inst Res & Adv Studies ICREA, Barcelona, Spain
:
irsiCaixa AIDS Res Inst, Badalona, Spain
Germans Trias & Pujol Res Inst IGTP, Can Ruti Campus, Badalona, Spain
:
irsiCaixa AIDS Res Inst, Badalona, Spain
:
irsiCaixa AIDS Res Inst, Badalona, Spain
Germans Trias & Pujol Res Inst IGTP, Can Ruti Campus, Badalona, Spain
Univ Vic Cent Univ Catalonia UVic UCC, Vic, Spain
:
irsiCaixa AIDS Res Inst, Badalona, Spain
Germans Trias & Pujol Res Inst IGTP, Can Ruti Campus, Badalona, Spain
Univ Vic Cent Univ Catalonia UVic UCC, Vic, Spain
Vergara-Alert, J:
UAB, Ctr Recerca Sanitat Anim CReSA, IRTA, Campus UAB, Barcelona 08193, Catalonia, Spain
Segales, J:
UAB, Ctr Recerca Sanitat Anim CReSA, IRTA, Campus UAB, Barcelona 08193, Catalonia, Spain
UAB, Dept Sanitat & Anat Anim, Fac Vet, Campus UAB, Barcelona, Catalonia, Spain
Green Published, hybrid
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