23-29 novembre 2020
A mutant virus could be more efficient in replication and transmission
The spread of a viral pandemic may be a favourable environment for mutations potentially able to modify the development of the illness, its virulence, and the virus’ capacities for transmission.
SARS-CoV-2 possesses a correction activity as its genome is replicated. As a result there are relatively few mutations that accumulate over time in comparison with other viruses such as HIV. However, a D614G mutation has been detected: the amino acid aspartic acid has mutated with glycine in position 614. This mutation is situated within the Spike protein that is found on the surface of free viruses. Its interaction with the ACE2 cellular receptor allows the virus to penetrate into the cell.
This mutated strain has become the epidemic’s predominant strain. Patients infected with the mutated virus have a greater viral charge in the upper respiratory tract compared to the original viral strain (the field virus). This does not seem to alter the severity of the illness.
Nevertheless the impact of this mutation on the virus’ replication, its pathogenesis and its transmissibility remained badly understood. This is why researchers wished to measure these elements.
The first step was to carry out tests on the infectivity of different types of cell in the upper respiratory tract, to measure the virus’ capacity to multiply. We now know that the D614G mutation enables an increase in viral replication in the epithelial cells of the upper respiratory tract (ex vivo) which express a high level of ACE2 receptors. This research also allowed scientists to show that the mutation-bearing virus enters the laboratory’s cell lines more efficiently than the original virus.
Secondly, tests on transmissibility on hamsters (in vivo) demonstrated that the virus bearing the D614G mutation spread more quickly than the field virus.
Finally, tests on pathogenicity (tissue damage, inflammation, weight loss) were carried out on two transgenic animal models bearing the human ACE2 receptor (mouse and hamster). The pathogenicity of the mutated virus had not increased in the animals.
But how much do we know about the biochemical details of this mutation? The morphology of the virus’ Spike protein present on the surface of cells was observed using an electronic microscope. No significant difference was detected between the mutated virus and the field virus. In addition, experiments carried out with the antibodies and serum of patients infected with SARS-CoV-2 show that the D614G mutation does not alter the virus’ neutralising properties.
Taken together, these results suggest that approaches to the vaccine developed out of the field virus will be just as effective against the strain carrying the D614G mutation