PNAS: The secret of new coronavirus spreading between cells

A new study found that the new coronavirus has taken some secret actions to survive, and one of its secrets to success is to escape from the immune system through cell-to-cell transmission
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Cell culture experiments show that SARS-CoV-2, which causes COVID-19, restricts the release of virus particles that can be inactivated by antibodies.
They are hidden in the cell wall and spread between cells
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"This is basically a form of underground transmission," said lead author Shan-Lu Liu, a professor of virology in the Department of Veterinary Biological Sciences at Ohio State University and a researcher at the University's Retroviral Research Center
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"SARS-CoV-2 can effectively spread between cells because there is basically no blocker from host immunity
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Liu and colleagues also discovered some other enlightening details about SARS-CoV-2: The spike protein on the surface of the virus can achieve cell-to-cell transmission, but the virus's main receptor on the target cell-the spike Binding to target cells-not a necessary part of cell-to-cell propagation operations
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The research was published in the December 22 issue of PNAS
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One of the main points of this study is to compare SARS-cov -2 with the coronavirus after the SARS outbreak in 2003
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Research comparisons have shown that the mode of transmission of SARS in 2003 is different from SARS-CoV-2.
The former is when free-floating virus particles infect target cells by binding to a receptor surface (still susceptible to antibodies produced by previous infections and vaccines)
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The different efficacies of these two viruses were first demonstrated in experiments using pseudoviruses
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"For the intercellular transmission of SARS-CoV-2 and SARS-CoV, the spike protein is necessary and sufficient, because the only difference between these pseudoviruses is the spike protein
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Studying these differences more deeply, the researchers found that SARS-CoV-2 is also more capable than SARS-CoV in initiating fusion with the target cell membrane, which is another key step in the virus entry process
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Liu also found that the paradox is that too much cell membrane fusion can cause cell death, which actually interferes with cell-to-cell transmission
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Subsequently, the research team turned to the role of ACE2 receptors
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"There is no perfect correlation between SARS-CoV-2 infection and ACE2 levels," Liu said.
"The initial infection may require ACE2, but once the infection is established, the virus may no longer require ACE2 because it can spread between cells
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Finally, in the experiment of real SARS-CoV-2 virus detection on the blood samples of human COVID-19 patients, the researchers determined that the virus can evade the antibody response through cell-to-cell transmission, but in the cell-free mode of transmission, the antibody is And the virus is effective
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"We were able to confirm that cell-to-cell transmission is not sensitive to the suppression of antibodies from COVID patients or vaccinated people.
With the continuous emergence of SARS-CoV-2 variants, including the recent variant Omicron, cell-to-cell transmission is more effective for antibody neutralization.
Drug resistance may be something we should pay attention to
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In this sense, the development of effective antiviral drugs for other steps of viral infection is crucial
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There are still many unknown factors, including the exact mechanism of virus transmission between cells, how this may affect the individual's response to virus infection, and whether efficient cell-to-cell transmission will lead to the emergence and spread of new mutations
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This laboratory plans to use real viruses and human lung cells to conduct more studies to further explore these issues
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Original title:

SARS-CoV-2 spreads through cell-to-cell transmission https://pubmed.
ncbi.
nlm.
nih.
gov/34937699/