SARS-CoV-2 Can Infect Bone Marrow-Derived Macrophages And Alter The Expression Of Macrophage Chemotaxis And Osteoclast-Related Genes!
: A new study by Chinese researchers from Shanghai Jiao Tong University, Shanghai Sixth People’s Hospital, ShanghaiTech University, Guangzhou Medical University and also Chinese researchers based at the University of Western Australia has found that the SARS-CoV-2 coronavirus is able to infect bone marrow-derived macrophages (BMM) and alter the expression of macrophage chemotaxis and osteoclast-related genes.
To date, it is known that SARS-CoV-2 infection in human beings 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.
Alarmingly existing clinical data have suggested possible SARS-CoV-2 infection in human skeleton system.
According to the study abstract, the study team 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.
Most significantly 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
Utilizing single-cell RNA sequencing (scRNA-Seq), the study team characterized SARS-CoV-2 infection in BMMs.
It was found that SARS-CoV-2 entry on BMMs appeared to be dependent on the expression of neuropilin-1 (NRP1) rather than the widely recognized receptor ACE2.
Importantly 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.
The study findings 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.
The study findings were published on a preprint server and are currently being peer reviewed. https://www.biorxiv.org/content/10.1101/2021.04.14.439793v1
The study confirms that alter bone marrow macrophage (BMM)-to-osteoclast differentiation.
The COVID-19 pandemic
, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is primarily a respiratory illness.
While the pandemic evolves, researchers have observed a range of different ways that the virus can affect the body. Alongside the lungs, SARS-CoV-2 has been seen to affect other organs, including the heart, brain and gastrointestinal tract.
The Chinese study in China and Australia has shown that SARS-CoV-2 infection can affect bone marrow macrophage (BMM)-
to-osteoclast differentiation, which may impact the skeletal system.
The study team found that authentic SARS-CoV-2 could efficiently infect both human and mouse BMMs and alter the expression of macrophage chemotaxis and osteoclast-related genes.
The SARS-CoV-2 is continuing to ravage the globe despite the massive ongoing vaccination programmes. To date, over 141 million cases have been reported, and more than 3.02 million people have died.
Infected COVID-19 patients develop various clinical manifestations, including severe acute pulmonary disease, liver dysfunction, kidney injury, heart damage, pancreatic and gastrointestinal symptoms, and loss of smell or taste.
To date however, scientists have not yet determined the effect of COVID-19 on the skeletal system. Past evidence showed the incidence of COVID-19-associated calcium metabolic disorders and osteoporosis.
Doctors have also observed that severely ill COVID-19 patients can have decreased blood calcium and phosphorus levels, compared with those experiencing moderate symptoms. This suggests that SARS-CoV-2 could also infect the skeletal system.
Typically osteoclasts are major cell types found in bones. Dysfunction in these cells may cause disturbed bone metabolism, including osteoporosis, which is characterized by decreased bone calcium and phosphorus levels.
It is known that osteoclasts generate from the fusion of bone marrow from macrophage (BMM) precursors in the presence of macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa-B ligand (RANKL)16.
The macrophages sense and respond to viral infection and maintain tissue homeostasis. When macrophage response is altered, it can lead to the rapid progression of COVID-19.
Importantly in SARS-CoV-2 patients, COVID-19 patient-derived macrophages contain SARS-CoV-2 nucleoproteins.
The study team investigated the interactions between SARS-CoV-2 and BMMS. They also found that SARS-CoV-2 could efficiently infect BMMs through the NRP1-dependent manner.
The team also characterized SARS-CoV-2 infection in BMMs and showed that NRP1 played a significant role during infection. This could pave the way to better understand the causal link between COVID-19 and bone metabolism.
The team analyzed the expression of nucleocapsid protein in control and infected BMMs to determine the infectivity of SARS-CoV-2.
The study team also conducted SMART transcriptomic analysis, finding that authentic SARS-CoV-2 genes were markedly expressed in infected mouse BMMs, with nucleocapsid genes having the highest expression.
Surprisingly, the researchers also found that the entry of SARS-CoV-2 on BMMs relied on the expression of NRP1, rather than the widely known angiotensin-converting enzyme 2 (ACE2) receptor.
Highly distinct from brain macrophages that exhibited aging-dependent NRP1 expression, BMMs from neonatal and aged mice had constant NRP1 expression, making them susceptible target cells for SARS-CoV-2 infection. The study suggests that NRP1 can mediate SARS-CoV-2 infection in BMMs.
The study team recommends further studies and more comprehensive analysis to help clarify SARS-CoV-2’s impact on the skeletal system, which may also help discover new treatments for COVID-19, especially those experiencing long-term symptoms.
The ongoing COVID-19 pandemic remains a global health threat. Determining potential impacts on the human body can help reduce the number of deaths tied to infection and also understand the potential long term health threats of the disease.
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