The HDL-transporting scavenger receptor B1 promotes viral infection through endolysosomal acidification

  • iScience. 2025 Apr 24;28(6):112501. doi: 10.1016/j.isci.2025.112501.
Jill McConnell  1 Sun-Young Lim  2  3 Thomas Cicuto  1 Ping Liu  2 Pyae Phyo Kyawe  2 Manish Kandpal  1 Evan S Bradley  1 Kendi Okuda  2 Neal Silverman  2 Jennifer P Wang  2  4 William M McDougall  1
Affiliations
  • 1. Department of Microbiology and Physiological Systems, University of Massachusetts Chan Medical School, 364 Plantation Street, Worcester, MA 01605, USA.
  • 2. Department of Medicine, University of Massachusetts Chan Medical School, 364 Plantation Street, Worcester, MA 01605, USA.
  • 3. Immunology and Microbiology Program, Morningside Graduate School of Biomedical Sciences, University of Massachusetts Chan Medical School, 364 Plantation Street, Worcester, MA 01605, USA.
  • 4. Diabetes Center of Excellence, University of Massachusetts Chan Medical School, 364 Plantation Street, Worcester, MA 01605, USA.
Abstract

Virus infections pose a continuous threat to human health and can result in millions of deaths per year. SARS-CoV-2 Infection has been linked to the high-affinity high-density lipoprotein (HDL) receptor scavenger receptor class B, type 1 (SR-B1). Mechanisms by which SR-B1 supports SARS-CoV-2 Infection and replication, as well as the breadth of viruses that exploit this receptor, are incompletely defined. In evaluating the role of SR-B1 in the biology of Infection with SARS-CoV-2, influenza A virus, and vesicular stomatitis virus, we show that SR-B1 chemical inhibition or knockout adversely affects Infection for these viruses. Inhibiting SR-B1 results in lack of acidification in the endolysosomal compartment and entrapment of SARS-CoV-2 in endosomal-lysosomal vesicles. These findings together indicate that SR-B1, and possibly HDL, is critical for successful SARS-CoV-2 trafficking through a pH-dependent vesicular entry pathway. Our work provides insights into how SR-B1 can impact viral Infection in human lung cells.

Keywords
Biochemistry; Biological sciences; Cell biology; Microbiology; Natural sciences; Viral microbiology; Virology.
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