Neuropilin-1 Mediates SARS-CoV-2 Infection in Bone Marrow-derived Macrophages

SARS-CoV-2 infection in human can cause medical complications across various tissues and organs. Despite of the advances to understanding the pathogenesis of SARS-CoV-2, its tissue tropism and interactions with host cells have not been fully understood. Existing clinical data have suggested possible...

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Bibliographic Details
Published in:bioRxiv 2021-04
Main Authors: Gao Junjie, Hong, Mei, Sun, Jing, Li, Hao, Huang Yuege, Tang, Yanhong, Duan Linwei, Liu, Delin, Wang, Qiyang, Gao Youshui, Song, Ke, Zhao Jincun, Zhang, Changqing, Liu, Jia
Format: Article
Language:English
Subjects:
ACE2
Aging
Angiotensin
Angiotensin-converting enzyme 2
Bone marrow
Chemotaxis
Immunofluorescence
Infections
Macrophages
Neonates
Neuropilin
Osteoclastogenesis
Osteoclasts
Peptidyl-dipeptidase A
Severe acute respiratory syndrome coronavirus 2
Skeleton
Tropism
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Summary:SARS-CoV-2 infection in human can cause medical complications across various tissues and organs. Despite of the advances to understanding the pathogenesis of SARS-CoV-2, its tissue tropism and interactions with host cells have not been fully understood. Existing clinical data have suggested possible SARS-CoV-2 infection in human skeleton system. In the present study, we found that authentic SARS-CoV-2 could efficiently infect human and mouse bone marrow-derived macrophages (BMMs) and alter the expression of macrophage chemotaxis and osteoclast-related genes. Importantly, in a mouse SARS-CoV-2 infection model that was enabled by the intranasal adenoviral (AdV) delivery of human angiotensin converting enzyme 2 (hACE2), SARS-CoV-2 was found to be present in femoral BMMs as determined by in situ immunofluorescence analysis. Using single-cell RNA sequencing (scRNA-Seq), we characterized SARS-CoV-2 infection in BMMs. Importantly, SARS-CoV-2 entry on BMMs appeared to be dependent on the expression of neuropilin-1 (NRP1) rather than the widely recognized receptor ACE2. It was also noted that unlike brain macrophages which displayed aging-dependent NRP1 expression, BMMs from neonatal and aged mice had constant NRP1 expression, making BMMs constantly vulnerable target cells for SARS-CoV-2. Furthermore, it was found that the abolished SARS-CoV-2 entry in BMM-derived osteoclasts was associated with the loss of NRP1 expression during BMM-to-osteoclast differentiation. Collectively, our study has suggested that NRP1 can mediate SARS-CoV-2 infection in BMMs, which precautions the potential impact of SARS-CoV-2 infection on human skeleton system. Competing Interest Statement The authors have declared no competing interest.
DOI:10.1101/2021.04.14.439793