Your browser doesn't support javascript.
Biodistribution and Cellular Internalization of Inactivated SARS-CoV-2 in Wild-Type Mice.
Hudák, Anett; Morgan, Gareth; Bacovsky, Jaromir; Patai, Roland; Polgár, Tamás F; Letoha, Annamária; Pettko-Szandtner, Aladar; Vizler, Csaba; Szilák, László; Letoha, Tamás.
  • Hudák A; Pharmacoidea Ltd., H-6726 Szeged, Hungary.
  • Morgan G; Boeckeler Instruments, Inc., Tucson, AZ 85714, USA.
  • Bacovsky J; Delong Instruments a.s., 612 00 Brno, Czech Republic.
  • Patai R; Institute of Biophysics, Biological Research Centre, H-6726 Szeged, Hungary.
  • Polgár TF; Institute of Biophysics, Biological Research Centre, H-6726 Szeged, Hungary.
  • Letoha A; Theoretical Medicine Doctoral School, Faculty of Medicine, University of Szeged, H-6720 Szeged, Hungary.
  • Pettko-Szandtner A; Department of Medicine, Albert Szent-Györgyi Clinical Center, Faculty of Medicine, University of Szeged, H-6720 Szeged, Hungary.
  • Vizler C; Laboratory of Proteomics Research, Biological Research Centre, H-6726 Szeged, Hungary.
  • Szilák L; Institute of Biochemistry, Biological Research Centre, H-6726 Szeged, Hungary.
  • Letoha T; Pharmacoidea Ltd., H-6726 Szeged, Hungary.
Int J Mol Sci ; 23(14)2022 Jul 09.
Article in English | MEDLINE | ID: covidwho-1964001
ABSTRACT
Despite the growing list of identified SARS-CoV-2 receptors, the human angiotensin-converting enzyme 2 (ACE2) is still viewed as the main cell entry receptor mediating SARS-CoV-2 internalization. It has been reported that wild-type mice, like other rodent species of the Muridae family, cannot be infected with SARS-CoV-2 due to differences in their ACE2 receptors. On the other hand, the consensus heparin-binding motif of SARS-CoV-2's spike protein, PRRAR, enables the attachment to rodent heparan sulfate proteoglycans (HSPGs), including syndecans, a transmembrane HSPG family with a well-established role in clathrin- and caveolin-independent endocytosis. As mammalian syndecans possess a relatively conserved structure, we analyzed the cellular uptake of inactivated SARS-CoV-2 particles in in vitro and in vivo mice models. Cellular studies revealed efficient uptake into murine cell lines with established syndecan-4 expression. After intravenous administration, inactivated SARS-CoV-2 was taken up by several organs in vivo and could also be detected in the brain. Internalized by various tissues, inactivated SARS-CoV-2 raised tissue TNF-α levels, especially in the heart, reflecting the onset of inflammation. Our studies on in vitro and in vivo mice models thus shed light on unknown details of SARS-CoV-2 internalization and help broaden the understanding of the molecular interactions of SARS-CoV-2.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Tissue Distribution / Virus Internalization / SARS-CoV-2 / COVID-19 Limits: Animals / Humans Language: English Year: 2022 Document Type: Article Affiliation country: Ijms23147609

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: International databases Database: MEDLINE Main subject: Tissue Distribution / Virus Internalization / SARS-CoV-2 / COVID-19 Limits: Animals / Humans Language: English Year: 2022 Document Type: Article Affiliation country: Ijms23147609