CLN7/MFSD8 may be an important factor for SARS-CoV-2 cell entry

Elena-Sofia Heinl; Sebastian Lorenz; Barbara Schmidt; Nouf Nasser M Laqtom; Joseph R Mazzulli; Laetitia Francelle; Timothy W Yu; Benjamin Greenberg; Stephan Storch; Ines Tegtmeier; Helga Othmen; Katja Maurer; Malin Steinfurth; Ralph Witzgall; Vladimir Milenkovic; Christian H Wetzel; Markus Reichold

doi:10.1016/j.isci.2022.105082

CLN7/MFSD8 may be an important factor for SARS-CoV-2 cell entry

iScience. 2022 Oct 21;25(10):105082. doi: 10.1016/j.isci.2022.105082. Epub 2022 Sep 6.

Authors

Elena-Sofia Heinl¹, Sebastian Lorenz¹, Barbara Schmidt², Nouf Nasser M Laqtom³, Joseph R Mazzulli⁴, Laetitia Francelle⁴, Timothy W Yu^{5

6}, Benjamin Greenberg⁷, Stephan Storch⁸, Ines Tegtmeier¹, Helga Othmen^{1

9}, Katja Maurer¹, Malin Steinfurth¹, Ralph Witzgall⁹, Vladimir Milenkovic¹⁰, Christian H Wetzel¹⁰, Markus Reichold¹

Affiliations

¹ Medical Cell Biology, University Regensburg, 93053 Regensburg, Germany.
² Institute of Clinical Microbiology and Hygiene, University of Regensburg, 93053 Regensburg, Germany.
³ Departments of Chemical Engineering and Genetics, Stanford University, Stanford, CA 94305, USA.
⁴ The Ken and Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
⁵ Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA.
⁶ Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
⁷ Department of Neurology, UT Southwestern Medical Center, Dallas, TX, USA.
⁸ Children's Hospital Biochemistry, University Medical Center Hamburg Eppendorf, 20246 Hamburg, Germany.
⁹ Institute for Molecular and Cellular Anatomy, University Regensburg, 93053 Regensburg, Germany.
¹⁰ Department of Psychiatry and Psychotherapy, University of Regensburg, 93053 Regensburg, Germany.

Abstract

The SARS-CoV-2 virus has triggered a worldwide pandemic. According to the BioGrid database, CLN7 (MFSD8) is thought to interact with several viral proteins. The aim of this work was to investigate a possible involvement of CLN7 in the infection process. Experiments on a CLN7-deficient HEK293T cell line exhibited a 90% reduced viral load compared to wild-type cells. This observation may be linked to the finding that CLN7 ko cells have a significantly reduced GM1 content in their cell membrane. GM1 is found highly enriched in lipid rafts, which are thought to play an important role in SARS-CoV-2 infection. In contrast, overexpression of CLN7 led to an increase in viral load. This study provides evidence that CLN7 is involved in SARS-CoV-2 infection. This makes it a potential pharmacological target for drug development against COVID-19. Furthermore, it provides insights into the physiological function of CLN7 where still only little is known about.

Keywords: Cell biology; Virology.

Grants and funding

R21 NS125847/NS/NINDS NIH HHS/United States