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

Junjie, G.; Hong, M.; Jing, S.; Hao, L.; Yuege, H.; Yanhong, T.; Linwei, D.; Delin, L.; Qiyang, W.; Youshui, G.; Ke, S.; Jincun, Z.; Changqing, Z.; Jia, L.

doi:10.1101/2021.04.14.439793

bioRxiv · 10.1101/2021.04.14.439793

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

Junjie, G.·Hong, M.·Jing, S.·Hao, L.·Yuege, H.·Yanhong, T.·Linwei, D.·Delin, L.·Qiyang, W.·Youshui, G.·Ke, S.·Jincun, Z.·Changqing, Z.·Jia, L.

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Abstract

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.

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Junjie, G., Hong, M., Jing, S., Hao, L., Yuege, H., Yanhong, T., Linwei, D., Delin, L., Qiyang, W., Youshui, G., Ke, S., Jincun, Z., Changqing, Z., Jia, L.. 2021-04-14. Neuropilin-1 Mediates SARS-CoV-2 Infection in Bone Marrow-derived Macrophages. https://doi.org/10.1101/2021.04.14.439793

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