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.
【저자키워드】 severe acute respiratory syndrome coronavirus 2, Neuropilin-1, bone marrow-derived macrophages, osteoclast differentiation, 【초록키워드】 COVID-19, coronavirus disease, SARS-CoV-2, Coronavirus disease 2019, ACE2, coronavirus, Pathogenesis, macrophages, B.1.351, neutralization, SARS-COV-2 infection, Infection, severe acute respiratory syndrome Coronavirus, virus, angiotensin-converting enzyme 2, metabolism, Single-cell RNA sequencing, Bone marrow, humans, RNA sequencing, Cluster, Complication, NRP1, Neuropilin-1, receptor, Mouse models, in vivo, mouse model, expression, patients, calcium, COVID-19 patients, neuropilin, Evidence, Interaction, Analysis, angiotensin, bone marrow-derived macrophages, host cells, host cell, tissue tropism, phosphorus, acute respiratory syndrome, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, Clinical data, SARS-CoV-2 entry, damage, wild-type, organs, knockdown, various tissues, pathogenesis of SARS-CoV-2, susceptible, Human skeleton, phosphorus metabolism, identify, significantly, investigated, provide, dependent on, various tissue, impede, inhibit SARS-CoV-2, marrow-derived macrophage, 【제목키워드】 SARS-CoV-2, differentiation, bone, osteoclast,