Study finds SARS-CoV-2 goes underground to spread from cell to cell


A new study has found that SARS-CoV-2 hid from the immune system by spreading from cell to cell. The research has been published in the “Proceedings of the National Academy of Sciences Journal”.

“It’s basically a form of transmission underground,” said senior author Shan-Lu Liu, professor of virology in the Department of Veterinary Biosciences at Ohio State University and a researcher at the Center for Retrovirus Research at the Ohio State University. university. “SARS-CoV-2 can spread efficiently from cell to cell because there is essentially no blocker of the host’s immunity. Target cells become donor cells, and it just becomes a wave of spread, because the virus may not come out of the cells, “Liu added.

Liu and his colleagues found other telling details about SARS-CoV-2: the spike protein on its surface alone enabled cell-to-cell transmission, and yet the main receptor for the virus on target cells – to which the tip is bound – is not a necessary part of the cell-to-cell transmission operation. In addition, they found that neutralizing antibodies are less effective against the virus when it spreads through cells. A major point of this study was to compare SARS-CoV-2 to the coronavirus that caused the 2003 SARS epidemic, known as SARS-CoV. The results helped explain why, while the first outbreak resulted in much higher death rates and lasted only eight months, we are on the verge of breaking past the two-year mark of the current pandemic, the majority of the cases being asymptomatic, Liu said.

The comparison showed that SARS-CoV that caused SARS in 2003 was more effective than SARS-CoV-2 at what is known as cell-free transmission when free-floating viral particles infected target cells by binding. to a receptor on their surface – but also remained vulnerable to antibodies produced by previous infection and vaccines. SARS-CoV-2, on the other hand, is more efficient at cell-to-cell transmission, making it more difficult to neutralize with antibodies. The different efficiencies of viruses were first demonstrated in experiments using pseudoviruses – a non-infectious viral core decorated with the two types of coronavirus spike proteins on the surface.

“The spike protein is necessary and sufficient for cell-to-cell transmission of SARS-CoV-2 and SARS-CoV, because the only difference between these pseudoviruses was the spike proteins,” said Liu, also program director. from the Virus and Emerging Pathogen Program of the Ohio State Institute of Infectious Diseases. Looking further into these differences, the researchers found that SARS-CoV-2 is also more capable than SARS-CoV of initiating fusion with a target cell membrane, another key step in the viral entry process. And this stronger fusion action was associated with the improved cell-to-cell transmission of the virus.

Ironically, too much cell membrane fusion leads to cell death and could actually interfere with cell-to-cell transmission, Liu also found. The team then looked at the role of the ACE2 receptor, a protein on the surface of cells that acts as a gateway for the entry of the virus that causes COVID-19. The researchers unexpectedly discovered that cells without or with low levels of ACE2 on their surface can be penetrated by the virus, allowing robust cell-to-cell transmission.

“There is no perfect correlation between SARS-CoV-2 infection and the level of ACE2,” Liu said. “ACE2 may be needed for the initial infection, but once infection is established, the virus may no longer need ACE2 because it can spread from cell to cell,” Liu added.

Finally, in experiments testing blood samples from human patients with COVID-19 against the genuine SARS-CoV-2 virus, the researchers determined that the virus could evade an antibody response through cell-to-cell transmission, but that neutralization of virus antibodies in the cell-free mode of transmission was effective. “We were able to confirm that cell-to-cell transmission is not susceptible to inhibition by antibodies from COVID patients or vaccinated individuals,” Liu said.

“Resistance of cell-to-cell transmission to neutralization of antibodies is probably something we should watch out for as SARS-CoV-2 variants continue to emerge, including the most recent, Omicron. In this sense, developing effective antiviral drugs targeting other stages of viral infection is critical, “Liu explained. There are still many unknowns, including the exact mechanism used by the virus to spread from cell to cell. the other, how it may influence individuals’ responses to viral infection and whether or not efficient cell-to-cell transmission has contributed to the emergence and spread of new variants. Liu’s lab plans further studies. using authentic virus and human lung cells to further explore these questions.

This work was supported by grants from the National Institutes of Health and funds from an anonymous private donor to the State of Ohio. Ohio State co-authors include Cong Zeng, Jack Evans, Tiffany King, Yi-Min Zheng, Eugene Oltz, Linda Saif, and Mark Peeples, also a researcher at Nationwide Children’s Hospital. Sean Whelan of the Washington University School of Medicine also contributed. (ANI)

(This story was not edited by Devdiscourse staff and is auto-generated from a syndicated feed.)


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