The entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
into human cells is an essential step for virus transmission and development
of COVID 19. Although the lung epithelial cells are its initial target,
SARS-CoV-2 also can infect endothelial cells. Endothelial cells are the
major constituents of the vascular system and cardiovascular complication is
a hallmark of severe COVID-19. Angiotensin-converting enzyme 2 (ACE2) is the
entry receptor for SARS-CoV-2. However, the possible involvement of other
cellular components in the viral entry is not fully understood.
A team of researchers from the Boston University School of Medicine (BUSM)
has identified extracellular vimentin as an attachment factor that
facilitates SARS-CoV-2 entry into human cells. Vimentin is a structural
protein that is widely expressed in the cells of mesenchymal origin such as
endothelial cells and a potential novel target against SARS-CoV-2, which
could block the infection of the SARS-CoV-2.
"Severe endothelial injury, vascular thrombosis, and obstruction of alveolar
capillaries (tiny air sacs scattered throughout the lungs) are common
features of severe COVID-19. Identification of vimentin as a host attachment
factor for SARS-CoV-2 can provide new insight into the mechanism of
SARS-CoV-2 infection of the vascular system and can lead to the development
of novel treatment strategies," said corresponding author Nader Rahimi,
Ph.D., associate professor of pathology & laboratory medicine at BUSM.
The researchers used liquid chromatography-tandem mass spectrometry
(LC-MS/MS) and identified vimentin as a protein that binds to the SARS-CoV-2
spike (S) protein and facilitates SARS-CoV-2 infection. They also found that
depletion of vimentin significantly reduces SARS-CoV-2 infection of human
endothelial cells. In contrast, over-expression of vimentin with ACE2
significantly increased the infection rate. "More importantly, we saw that
the CR3022 antibody inhibited the binding of vimentin with CoV-2-S-protein,
and neutralized SARS-CoV-2 entry into human cells," explained Rahimi.
These findings appear online in the Proceedings of the National Academy of
Sciences.
Reference:
Razie Amraei et al, Extracellular vimentin is an attachment factor that
facilitates SARS-CoV-2 entry into human endothelial cells, Proceedings of
the National Academy of Sciences (2022).
DOI: 10.1073/pnas.2113874119