Covid Virus Rapidly Evolves to Higher Infectivity during in Vitro Growth, Which May be Step toward Lower Virulence

They asked a simple question: Which mutations predominate when the SARS-CoV-2 virus that causes COVID-19 is grown in successive generations — called passages by virologists — in tissue culture? The UAB researchers found that SARS-CoV-2 isolates rapidly adapted as they grew in repeated passages in Vero E6 cells, a strain of kidney cells that is commonly used for virus propagation.

For one of the SARS-CoV-2 strains tested by UAB researchers — a strain from Washington state that was the first COVID-19 virus detected in the United States at the start of 2020 — the average number of infectious virus particles released from the cells was 100-fold less than the number of infectious particles released after four passages. Others have shown that the alphaviruses chikungunya, Venezuelan equine encephalitis, Ross River and Sindbis showed similar rapid evolution during growth in cell culture, including increased plaque size, a stronger interaction with heparan sulfate, and a stimulated spread of infection. Frolov said, “As with the heparan sulfate-binding mutants of other RNA+ viruses, the evolved SARS-CoV-2 may also be attenuated in vivo, particularly the double mutant that demonstrates the most adapted phenotype

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