SARS-CoV-2 virus can find alternative pathways to infect cells

Colored scanning electron micrographs of cells strongly infected with SARS-CoV-2 virus particles (red) (blue) isolated from patient samples. Image taken at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. Credit: NIAID

Early in the COVID-19 pandemic, scientists identified how SARS-CoV-2, the virus that causes COVID-19, invades cells and causes infection. All current COVID-19 vaccines and antibody-based therapies are designed to disrupt this pathway to cells that require a receptor called ACE2.

Researchers at Washington University in St. Louis School of Medicine have now discovered that a single mutation confers the ability to enter SARS-CoV-2. cell It goes through another route (a route that does not require ACE2). The ability to use alternative entry routes opens up the possibility of evading COVID-19 antibodies or vaccines, but researchers have found no evidence of such evasion. However, this finding indicates that the virus may change in unexpected ways and find new ways to cause infection.The study will be published on June 23 Cell report..

“This mutation occurred in one of the spots that changed significantly as the virus circulated. populationSebla Kutluay, Ph.D., co-author, assistant professor of molecular microbiology. Said: However, in this case, we discovered another way to infect human lung cells, an important cell type, and found that the virus acquired this ability through mutations known to occur in populations. did. This is definitely what we need to know more. “

This discovery was a coincidence. Last year, Kutluay and co-authors M. Ben Major, Ph.D., Alan A., and Edith L. Wolff, prominent professors of cell biology and physiology, found that SARS-infected intracellular molecules occur. I planned to study change. CoV-2. Most researchers are studying SARS-CoV-2 because the virus proliferates well in primate kidney cells, but Kutluay and Major are in lungs or other cells similar to naturally infected cells. I felt it was important to do research. To find more relevant cells capable of growing SARS-CoV-2, Kutluay and Major screened a panel of 10 lung and head and neck cell lines.

“Only the ones I included as a negative control could be infected,” said Major. “It was a human lung cancer cell line without detectable ACE2, so it was a crazy surprise.”

Kutluay, Major and colleagues-co-lead author and postdoctoral fellow Maritza Puray-Chavez, Ph.D., Kyle LaPak, Ph.D. , And co-author Dennis Goldfarb, Ph.D. , Ph.D. in Cell Biology and Physiology and Medicine, including Associate Professor, Stephen L. Brody, Ph.D. in Medicine, Dorothy R. and Hubert C. Moog, Ph.D. I found that the virus I was using was selected. It causes a mutation. The virus was originally obtained from a person at COVID-19, Washington, but as it propagated over time in the laboratory, it acquired mutations that led to changes in a single amino acid at position 484 of the virus spike. Did. protein. SARS-CoV-2 uses spikes to connect to ACE2, position 484 mutation.. Various mutations in the same position have been found in human and mouse viral variants, as well as in laboratory-grown viruses. Some of the mutations found in virus samples taken from people are identical to those found in those variants of Kutluay and Major. The alpha and beta mutants of concern have a mutation at position 484, but these mutations are different.

“This position is evolving over time in the population and in the lab,” said Major. “Given our data and other data, viruses may be under selective pressure to invade cells without the use of ACE2. In many ways, viruses that diversify their mechanisms. It’s scary to think of the world’s population fighting against it. It can infect cells. “

To determine if the ability to use alternative entry routes allowed the virus to escape the COVID-19 antibody or vaccine, researchers screened a panel of antibodies and screened the antibody panel. serum Use antibodies from people who have been vaccinated with COVID-19 or who have recovered from COVID-19 infection. Antibodies and sera were generally effective against mutated viruses, although there was some variability.

It is not yet clear whether alternative pathways work under real-world conditions when people are infected with SARS-CoV-2. Before researchers start addressing that question, they must find alternative receptors that the virus is using to enter cells.

“It could be Virus We will use ACE2 until there are no more cells containing ACE2 and then switch to using this alternative pathway, “says Kutluay. “This may be relevant in the body, but without knowing the receptors, we don’t know what the association will be.”

Major added, “That’s what we’re doing right now. What’s the receptor? If it’s not ACE2, what’s it?”

How SARS-CoV-2 mutants sacrifice tight binding for antibody avoidance

For more information:
Maritza Puray-Chavez et al, Systematic analysis of SARS-CoV-2 infection in ACE2-negative human airway cells, Cell report (2021). DOI: 10.1016 / j.celrep.2021.109364

Quote: SARS-CoV-2 virus is an infected cell obtained on June 25, 2021 from https: // (2021, You can find an alternative route to (June 25th) .html

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SARS-CoV-2 virus can find alternative pathways to infect cells

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