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Coronavirus mutation-does it matter?

Reporter : Irina Robu, PhD

Soon after SARS-CoV-2 was detected in China, scientists began analyzing viral sample and posting the genetic codes online. Mutations allowed researchers to track the spread by linking closely related viruses to understand how SARS-CoV-2 infects humans.  They recognized that SARS-CoV-2 encode their genome in RNA and tends to pick up mutations quickly as they are copied inside their hosts.  Yet,  sequencing data suggest that coronaviruses change more slowly than most RNA viruses, probably because of a proofreading enzyme that corrects fatal copying mutations.  In spite of the virus slow mutation rate, scientists have been able to classified more than 12,000 mutations in SARS-CoV-2 genomes.

Many scientists such as David Montefiori, a virologist who spent much of his career studying how chance mutations in HIV helps it evade the immune system thought that COVID-19 might cause the same thing.  His laboratory in collaboration with Dr. Bette Korber investigated several thousands of coronavirus sequences for mutations that might have changed virus properties around the world.

Compared to HIV, SARS-CoV-2 seems to be changing slower than it spreads, but one mutation is obvious. That mutation  includes a gene encoding the spike protein, which helps the virus particles penetrate cells. According to Korber, the 614^th amino acid position of the spike protein, the amino acid aspartate was replaced by glycine, because of a mutation, D614G that altered a single nucleotide in the virus’s 29,903-letter RNA code.

To observe whether D614G  mutation made the virus more transmissible, Montefiori evaluated its effects under laboratory conditions but he couldn’t study the natural SARS-CoV-2 virus in his lab, because of the biosafety containment required. So, he studied a genetically modified form of HIV that used the SARS-CoV-2 spike protein to infect cells. Such ‘pseudo virus’ particles are a workhorse of virology labs: they enable the safe study of deadly pathogens such as the Ebola virus, and they make it simpler to test the effects of mutations.

The strongest sign that D614G has a consequence on the spread of SARS-CoV-2 in humans comes from an ambitious UK effort called the COVID-19 Genomics UK Consortium, which has analyzed genomes of around 25,000 viral samples. From these data, researchers have identified more than 1,300 instances in which a virus entered the United Kingdom and spread, including examples of D- and G-type viruses.

What is clearly known is that D614G is an adaptation that helps the virus infect cells or compete with viruses that don’t carry the change, while at the same time altering a bit of information about how SARS-CoV-2 spreads between people and through a population.  Some scientists believe that D614G mutation should explain how SARS-CoV-2 fuses with cells and can use that process to develop a more efficient vaccine. 

At the present time, the evidence suggests that D614G doesn’t stop the immune system’s neutralizing antibodies from recognizing SARS-CoV-2, partly because the mutation is not in the spike protein’s receptor-binding domain.

SOURCE

https://www.nature.com/articles/d41586-020-02544-6?utm_source=Nature+Briefing