Work in the high security laboratory of the Institute for Virology and Immunology (IVI). Credit: IVI

Before new mutants of the coronavirus such as the British variant B.1.1.7 appeared, the SARS-CoV-2 variant with the name D614G had already mutated from the original SARS-CoV-2 pathogen that triggered the pandemic. D614G has spread quickly and is the most common variant in the world. This D614G mutation is retained in all newly emerging variants. An international team of researchers from Bern has now been able to demonstrate both in the laboratory and in animal models why the D614G variant was able to gain the upper hand over the original SARS-CoV-2 virus. “Our approach also enables us to characterize newly emerging mutations such as the British variant B.1.1.7 better and faster,” says Volker Thiel from the Institute for Virology and Immunology (IVI), one of the four main authors of the study. The results are extremely important in assessing the risk that new mutants will be widespread, as they show how a fitness benefit from virus variants can lead to higher transmission. First results were published earlier to enable a scientific discussion about a so-called preprint server. The results of the study have now been fully published in Nature.

The D614G variant carries a mutation in the spike protein that makes it easier for the virus to dock onto human cells. The researchers at IVI and in David E. Wentworth’s laboratory at the Centers for Disease Control and Prevention in Atlanta (USA) showed for the first time in human cell cultures from the upper respiratory tract and from the nose that the D614G variant binds and replicates more strongly also faster than the original virus. The increased replication of the D614G variant was also confirmed in vivo in a new mouse model that was first described in this study. These experiments were also carried out at the IVI in the group of Charaf Benarafa.

The new mutation is clearly taking hold

The spread of SARS-CoV-2 viruses can be better investigated in other animals than in mice. Hamsters and ferrets are well established in infection research and are particularly suitable for animal models. To compare the two variants, a mixture of equal parts of the original version of the SARS-CoV-2 virus and the D614G variant was applied to the nose of each animal under light anesthesia. After one day, experimentally infected animals were resumed with another healthy sentinel animal of the same species in order to assess the transmission of the two variants in direct competition with one another. The experiment was repeated with a total of six pairs of animals. In practically all sentinel animals, the proportion of SARS-CoV-2 viruses transmitted was massively dominated by the D614G variant at an early stage. The differentiation of the variants was carried out using the latest sequencing technology and PCR technology by Martin Beer’s team at the Friedrich Loeffler Institute of the Federal Research Center for Animal Health in Greifswald-Insel Riems (D). “Our study is characterized by the fact that we were able to clearly identify the more efficient transfer of the mutated variant in direct comparison with the original variant,” says Volker Thiel.

A fitness test for further mutations

This approach can even be used to test for a single mutation or a specific combination of mutations that are present in a number of currently circulating viral variants. The IVI is based on a cloning technique developed in Bern a year ago with which SARS-CoV-2 viruses can be reproduced exactly in the laboratory. For example, it is known that the British virus has not just one, but often more than 14 mutations, eight of which are in the spike protein. Thus, with the help of the cloning technique, any number of mutations of variants can be reproduced and used to compete with one another in the established cell cultures and animal models. The results show how individual mutations influence the fitness and transferability of new variants. “With our test strategy, we can quickly investigate why other, newly emerging virus variants have established themselves,” says Volker Thiel.

Similar research projects on infectious pathogens could also be carried out in the future at the newly established multidisciplinary center for infectious diseases and immunity (MCIDI) at the University of Bern.

The mutation in SARS-CoV-2 spike protein makes the virus up to eight times more infectious

More information:
Bin Zhou et al., SARS-CoV-2 Spike-D614G Alteration Improves Replication and Transmission, Nature (2021). DOI: 10.1038 / s41586-021-03361-1 Provided by the University of Bern

Quote: SARS-CoV-2 mutations in competition (2021, February 26) were accessed on February 26, 2021 from

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