The Alpha variant of SARS-CoV-2 – the first variant of concern – evolved mutations that allowed it to more efficiently suppress the immune system’s early response to infection, according to a new study led by scientists at the UC San Francisco’s Quantitative Biosciences Institute (QBI) and University College London.
The researchers have discovered that the variant has ramped up production of a protein that it uses to stifle infected cells’ immune-stimulating signals. The mutations responsible for this change likely help the Alpha variant evade immune detection and accelerates its transmission, and importantly similar mutations exist in Omicron. The findings are reported in the Dec. 23 issue of Nature.
The team, led by senior authors Nevan Krogan, PhD, of UCSF and Claire Jolly and Greg Towers, PhD, of University College, London, found that Alpha’s enhanced infectivity arose from mutations outside of “spike,” the proteins that have attracted much of scientists’ attention since the start of the pandemic. Spike, which the virus uses to enter the cells of its host, is critical to infection and is the target of all available COVID-19 vaccines. But it is just one of many tools that the virus uses to manipulate its host.
While scientists have closely monitored mutations in the spike region of new variants – Omicron has over 30 – Krogan emphasized that changes in other regions might also have important impact.
“The mutations in spike allow the virus to get into cells more effectively. But what about after the virus gets into cells? There may be other mutations that allow it to replicate more,” said Krogan, who also leads UCSF’s QBI and its Coronavirus Research Group (QCRG).