高密度脂蛋白转运清道夫受体B1通过内溶酶体酸化促进病毒感染

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2025-04-24 DOI:10.1016/j.isci.2025.112501

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

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引用次数: 0

摘要

病毒感染对人类健康构成持续威胁，每年可导致数百万人死亡。SARS-CoV-2感染与高亲和力高密度脂蛋白（HDL）受体清道夫受体B类1型（SR-B1）有关。SR-B1支持SARS-CoV-2感染和复制的机制，以及利用该受体的病毒的广度，尚未完全确定。在评估SR-B1在SARS-CoV-2、甲型流感病毒和水泡性口炎病毒感染生物学中的作用时，我们发现SR-B1的化学抑制或敲除对这些病毒的感染有不利影响。抑制SR-B1可导致内溶酶体腔室缺乏酸化和SARS-CoV-2在内溶酶体囊泡中的包裹。这些发现共同表明，SR-B1，可能还有HDL，对于通过ph依赖性囊泡进入途径成功转运SARS-CoV-2至关重要。我们的工作为SR-B1如何影响人类肺细胞中的病毒感染提供了见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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

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

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.

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来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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