The HDL-transporting scavenger receptor B1 promotes viral infection through endolysosomal acidification
Summary: 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-...
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| Language: | English |
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Elsevier
2025-06-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S258900422500762X |
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| author | Jill McConnell Sun-Young Lim Thomas Cicuto Ping Liu Pyae Phyo Kyawe Manish Kandpal Evan S. Bradley Kendi Okuda Neal Silverman Jennifer P. Wang William M. McDougall |
| author_facet | Jill McConnell Sun-Young Lim Thomas Cicuto Ping Liu Pyae Phyo Kyawe Manish Kandpal Evan S. Bradley Kendi Okuda Neal Silverman Jennifer P. Wang William M. McDougall |
| author_sort | Jill McConnell |
| collection | DOAJ |
| description | Summary: 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. |
| format | Article |
| id | doaj-art-48e959e5e4c64315abc1cac2ce71db9d |
| institution | Kabale University |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-48e959e5e4c64315abc1cac2ce71db9d2025-08-20T03:48:47ZengElsevieriScience2589-00422025-06-0128611250110.1016/j.isci.2025.112501The HDL-transporting scavenger receptor B1 promotes viral infection through endolysosomal acidificationJill McConnell0Sun-Young Lim1Thomas Cicuto2Ping Liu3Pyae Phyo Kyawe4Manish Kandpal5Evan S. Bradley6Kendi Okuda7Neal Silverman8Jennifer P. Wang9William M. McDougall10Department of Microbiology and Physiological Systems, University of Massachusetts Chan Medical School, 364 Plantation Street, Worcester, MA 01605, USADepartment of Medicine, University of Massachusetts Chan Medical School, 364 Plantation Street, Worcester, MA 01605, USA; Immunology and Microbiology Program, Morningside Graduate School of Biomedical Sciences, University of Massachusetts Chan Medical School, 364 Plantation Street, Worcester, MA 01605, USADepartment of Microbiology and Physiological Systems, University of Massachusetts Chan Medical School, 364 Plantation Street, Worcester, MA 01605, USADepartment of Medicine, University of Massachusetts Chan Medical School, 364 Plantation Street, Worcester, MA 01605, USADepartment of Medicine, University of Massachusetts Chan Medical School, 364 Plantation Street, Worcester, MA 01605, USADepartment of Microbiology and Physiological Systems, University of Massachusetts Chan Medical School, 364 Plantation Street, Worcester, MA 01605, USADepartment of Microbiology and Physiological Systems, University of Massachusetts Chan Medical School, 364 Plantation Street, Worcester, MA 01605, USADepartment of Medicine, University of Massachusetts Chan Medical School, 364 Plantation Street, Worcester, MA 01605, USADepartment of Medicine, University of Massachusetts Chan Medical School, 364 Plantation Street, Worcester, MA 01605, USA; Corresponding authorDepartment of Medicine, University of Massachusetts Chan Medical School, 364 Plantation Street, Worcester, MA 01605, USA; Diabetes Center of Excellence, University of Massachusetts Chan Medical School, 364 Plantation Street, Worcester, MA 01605, USA; Corresponding authorDepartment of Microbiology and Physiological Systems, University of Massachusetts Chan Medical School, 364 Plantation Street, Worcester, MA 01605, USA; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S258900422500762XNatural sciencesBiological sciencesBiochemistryCell biologyMicrobiologyViral microbiology |
| spellingShingle | Jill McConnell Sun-Young Lim Thomas Cicuto Ping Liu Pyae Phyo Kyawe Manish Kandpal Evan S. Bradley Kendi Okuda Neal Silverman Jennifer P. Wang William M. McDougall The HDL-transporting scavenger receptor B1 promotes viral infection through endolysosomal acidification iScience Natural sciences Biological sciences Biochemistry Cell biology Microbiology Viral microbiology |
| title | The HDL-transporting scavenger receptor B1 promotes viral infection through endolysosomal acidification |
| title_full | The HDL-transporting scavenger receptor B1 promotes viral infection through endolysosomal acidification |
| title_fullStr | The HDL-transporting scavenger receptor B1 promotes viral infection through endolysosomal acidification |
| title_full_unstemmed | The HDL-transporting scavenger receptor B1 promotes viral infection through endolysosomal acidification |
| title_short | The HDL-transporting scavenger receptor B1 promotes viral infection through endolysosomal acidification |
| title_sort | hdl transporting scavenger receptor b1 promotes viral infection through endolysosomal acidification |
| topic | Natural sciences Biological sciences Biochemistry Cell biology Microbiology Viral microbiology |
| url | http://www.sciencedirect.com/science/article/pii/S258900422500762X |
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