tetano
Editor, Senior Moderator
Adv Biol (Weinh)
. 2022 Feb 23;e2200007.
doi: 10.1002/adbi.202200007. Online ahead of print.
Neuropilin-1-Mediated SARS-CoV-2 Infection in Bone Marrow-Derived Macrophages Inhibits Osteoclast Differentiation
Junjie Gao[SUP] 1 [/SUP], Hong Mei[SUP] 2 [/SUP], Jing Sun[SUP] 3 [/SUP], Hao Li[SUP] 1 [/SUP], Yuege Huang[SUP] 2 4 5 6 [/SUP], Yanhong Tang[SUP] 3 [/SUP], Linwei Duan[SUP] 3 [/SUP], Delin Liu[SUP] 7 [/SUP], Yidan Pang[SUP] 1 [/SUP], Qiyang Wang[SUP] 1 [/SUP], Youshui Gao[SUP] 1 [/SUP], Ke Song[SUP] 2 [/SUP], Jincun Zhao[SUP] 3 [/SUP], Changqing Zhang[SUP] 1 [/SUP], Jia Liu[SUP] 2 4 5 [/SUP]
Affiliations
Abstract
In humans, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause medical complications across various tissues and organs. Despite 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 revealed disordered calcium and phosphorus metabolism in Coronavirus Disease 2019 (COVID-19) patients, suggesting possible infection or damage in the human skeleton system by SARS-CoV-2. Herein, SARS-CoV-2 infection in mouse models with wild-type and beta strain (B.1.351) viruses is investigated, and it is found that bone marrow-derived macrophages (BMMs) can be efficiently infected in vivo. Single-cell RNA sequencing (scRNA-Seq) analyses of infected BMMs identify distinct clusters of susceptible macrophages, including those related to osteoblast differentiation. Interestingly, SARS-CoV-2 entry on BMMs is dependent on the expression of neuropilin-1 (NRP1) rather than the widely recognized receptor angiotensin-converting enzyme 2 (ACE2). The loss of NRP1 expression during BMM-to-osteoclast differentiation or NRP1 neutralization and knockdown can significantly inhibit SARS-CoV-2 infection in BMMs. Importantly, it is found that authentic SARS-CoV-2 infection impedes BMM-to-osteoclast differentiation. Collectively, this study provides evidence for NRP1-mediated SARS-CoV-2 infection in BMMs and establishes a potential link between disturbed osteoclast differentiation and disordered skeleton metabolism in COVID-19 patients.
Keywords: bone marrow-derived macrophages; neuropilin-1; osteoclast differentiation; severe acute respiratory syndrome coronavirus 2.
. 2022 Feb 23;e2200007.
doi: 10.1002/adbi.202200007. Online ahead of print.
Neuropilin-1-Mediated SARS-CoV-2 Infection in Bone Marrow-Derived Macrophages Inhibits Osteoclast Differentiation
Junjie Gao[SUP] 1 [/SUP], Hong Mei[SUP] 2 [/SUP], Jing Sun[SUP] 3 [/SUP], Hao Li[SUP] 1 [/SUP], Yuege Huang[SUP] 2 4 5 6 [/SUP], Yanhong Tang[SUP] 3 [/SUP], Linwei Duan[SUP] 3 [/SUP], Delin Liu[SUP] 7 [/SUP], Yidan Pang[SUP] 1 [/SUP], Qiyang Wang[SUP] 1 [/SUP], Youshui Gao[SUP] 1 [/SUP], Ke Song[SUP] 2 [/SUP], Jincun Zhao[SUP] 3 [/SUP], Changqing Zhang[SUP] 1 [/SUP], Jia Liu[SUP] 2 4 5 [/SUP]
Affiliations
- PMID: 35195371
- DOI: 10.1002/adbi.202200007
Abstract
In humans, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause medical complications across various tissues and organs. Despite 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 revealed disordered calcium and phosphorus metabolism in Coronavirus Disease 2019 (COVID-19) patients, suggesting possible infection or damage in the human skeleton system by SARS-CoV-2. Herein, SARS-CoV-2 infection in mouse models with wild-type and beta strain (B.1.351) viruses is investigated, and it is found that bone marrow-derived macrophages (BMMs) can be efficiently infected in vivo. Single-cell RNA sequencing (scRNA-Seq) analyses of infected BMMs identify distinct clusters of susceptible macrophages, including those related to osteoblast differentiation. Interestingly, SARS-CoV-2 entry on BMMs is dependent on the expression of neuropilin-1 (NRP1) rather than the widely recognized receptor angiotensin-converting enzyme 2 (ACE2). The loss of NRP1 expression during BMM-to-osteoclast differentiation or NRP1 neutralization and knockdown can significantly inhibit SARS-CoV-2 infection in BMMs. Importantly, it is found that authentic SARS-CoV-2 infection impedes BMM-to-osteoclast differentiation. Collectively, this study provides evidence for NRP1-mediated SARS-CoV-2 infection in BMMs and establishes a potential link between disturbed osteoclast differentiation and disordered skeleton metabolism in COVID-19 patients.
Keywords: bone marrow-derived macrophages; neuropilin-1; osteoclast differentiation; severe acute respiratory syndrome coronavirus 2.