Virus causing COVID-19 can find alternate route to infect cells: study

CHICAGO, June 25 — Researchers at Washington University School of Medicine in St. Louis have found that a single mutation gives SARS-CoV-2 the ability to enter cells through another route — one that does not require ACE2.
To find more relevant cells capable of growing SARS-CoV-2, the researchers screened a panel of 10 lung and head-and-neck cell lines and discovered that the virus they were using for experiments had picked up a mutation. The virus had originally been obtained from a person in Washington state with COVID-19, but as it was grown over time in the laboratory, it had acquired a mutation that led to a change of a single amino acid at position 484 in the virus’s spike protein.
SARS-CoV-2 uses spike to attach to ACE2, and position 484 is a hot spot for mutations. A variety of mutations at the same position have been found in viral variants from people and mice, and in viruses grown in the lab. The Alpha and Beta variants of concern have mutations at position 484, although those mutations are different.
“This position is evolving over time within the human population and in the lab,” said co-senior author M. Ben Major, a professor of cell biology and physiology. “Given our data and those of others, it is possible that the virus is under selective pressure to get into cells without using ACE2. In so many ways, it is scary to think of the world’s population fighting a virus that is diversifying the mechanisms by which it can infect cells.”
To determine whether the ability to use an alternative entry pathway allowed the virus to escape COVID-19 antibodies or vaccines, the researchers screened panels of antibodies and blood serum with antibodies from people who have been vaccinated for COVID-19 or recovered from COVID-19 infection. There was some variation, but in general, the antibodies and blood sera were effective against the virus with the mutation.
It is not yet clear whether the alternative pathway comes into play under real-world conditions when people are infected with SARS-CoV-2. Before the researchers can begin to address that question, they must find the alternative receptor that the virus is using to get into cells.
“It is possible that the virus uses ACE2 until it runs out of cells with ACE2, and then it switches over to using this alternative pathway,” said co-senior author Sebla Kutluay, an assistant professor of molecular microbiology. “This might have relevance in the body, but without knowing the receptor, we cannot say what the relevance is going to be.”
The study was published Wednesday in Cell Reports.

– Xinhua