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A critical role for MSR1 in vesicular stomatitis virus infection of the central nervous system
- Source :
- iScience, Vol 24, Iss 6, Pp 102678-(2021), iScience
- Publication Year :
- 2021
- Publisher :
- Elsevier, 2021.
-
Abstract
- Summary Macrophage scavenger receptor 1 (MSR1) plays an important role in host defense to bacterial infections, M2 macrophage polarization, and lipid homeostasis. However, its physiological function in viral pathogenesis remains poorly defined. Herein, we report that MSR1 facilitates vesicular stomatitis virus (VSV) infection in the central nervous system. Msr1-deficient (Msr1−/−) mice presented reduced morbidity, mortality, and viral loads in the spinal cord following lethal VSV infection, along with normal viremia and innate immune responses, compared to Msr1+/− littermates and wild-type mice. Msr1 expression was most significantly upregulated in the spinal cord, the predominant target of VSV. Mechanistically, through its extracellular domains, MSR1 interacted with VSV surface glycoprotein and facilitated its cellular entry in a low-density lipoprotein receptor-dependent manner. In conclusion, our results demonstrate that MSR1 serves as a cofactor for VSV cellular entry and facilitates its infection preferentially in the spinal cord.<br />Graphical abstract<br />Highlights • MSR1 contributes to VSV pathogenesis in mice • MSR1 is highly upregulated and facilitates VSV infection in the central nervous system • MSR1 facilitates cellular entry of VSV in an LDLR family-dependent manner • MSR1 interacts with VSV glycoprotein G via its extracellular domains<br />Molecular physiology; Neuroscience; Virology; Cell biology
- Subjects :
- 0301 basic medicine
Cell biology
Viral pathogenesis
viruses
Science
Central nervous system
Viremia
02 engineering and technology
Article
03 medical and health sciences
Downregulation and upregulation
Virology
medicine
Receptor
Molecular physiology
Multidisciplinary
Innate immune system
biology
021001 nanoscience & nanotechnology
biology.organism_classification
medicine.disease
M2 Macrophage
030104 developmental biology
medicine.anatomical_structure
Vesicular stomatitis virus
0210 nano-technology
Viral load
Neuroscience
Subjects
Details
- Language :
- English
- ISSN :
- 25890042
- Volume :
- 24
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- iScience
- Accession number :
- edsair.doi.dedup.....a6fef8deeec6314d71ddb22a1daaab20