All viruses mutate over time, it is a common occurrence in nature. This is no different for SARS-CoV-2, the virus that causes COVID-19. SARS-CoV-2 has had thousands of mutations since the original sequence of the virus was first identified over a year ago. Most of the time, these mutations don't change the behavior of the virus, and they are thought of as "passenger" mutations the virus carries with it as it continues to spread.
However, once in a while, some of the mutations turn out to beneficial to the virus. Depending on where they occur, it may help the virus to become more infectious and spread more rapidly, or it could help the virus evade the immune system better by making it less detectable. Various new variants of SARS-CoV-2 have recently been described, and many raised alarm bells due to the fact that the virus started to behave differently from the original variants, seemingly becoming more transmissible and/or less detectable.
Now, new research from the University of Pittsburgh School of Medicine has shown that SARS-CoV-2 may be selectively deleting fragments of the genetic sequence that codes for an important part of the virus, the spike protein on its surface. The spike protein is used by the virus to latch onto cells to infect them, and this is also the part of the virus that is targeted by antibodies, allowing the immune system to detect the virus and remove it.
“You can’t fix what’s not there,” said study senior author Paul Duprex, PhD, director of the Center for Vaccine Research at the University of Pittsburgh in a statement. “Once it’s gone, it’s gone, and if it’s gone in an important part of the virus that the antibody ‘sees,’ then it’s gone for good.”
The study, published in the journal Science, shows how the small deletions of fragments in the genetic code responsible for the structure of the spike protein are causing it to become more resistant to neutralizing antibodies. This results in a form of adaptive evolution, as the proofreading mechanism in the virus that should normally detect these mistakes during replication and fix them is not catching the fragment deletions, which results in a permanent change to the SARS-CoV-2 sequence, and this is altering the virus evolution and behavior.
Multiple antibodies (green and red) bind SARS-CoV-2 spike protein within cells (blue) when there are no deletions (LEFT). Spike protein deletions stop neutralizing antibody from binding (absence of green) but other antibodies (red) still attach very well (RIGHT). Recurrent deletion generates variants that escape from neutralization. Image Credit: Kevin McCarthy and Paul Duprex
Furthermore, more research needs to done to understand just how the South African and UK variants might be able to evade different antibodies, so that vaccine strategies could be informed of how to make changes in the future to tackle the virus most effectively.
