2. Academic Validation
  3. The HDL-transporting scavenger receptor B1 promotes viral infection through endolysosomal acidification

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

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.
PMID: 40475258 DOI: 10.1016/j.isci.2025.112501
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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