Mutations of SARS-CoV-2 in competition


Mutations of SARS-CoV-2 in competition

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

Before the emergence of new mutants of the coronavirus, such as the British variant B.1.1.7, the SARS-CoV-2 variant named D614G had already mutated from the original SARS-CoV-2 pathogen that triggered the pandemic. D614G quickly spread to become the most abundant variant in the world and this D614G mutation remains in all new emerging variants. An international team including Bernese researchers has now been able to demonstrate 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 allows us to better and more quickly characterize emerging mutations such as the British variant B.1.1.7”, explains Volker Thiel of the Institute of Virology and Immunology (IVI), one of the four main authors of the study. The results are extremely important in assessing the risk of new mutants becoming rampant, as they show how a fitness advantage of viral variants can lead to higher transmission. The first results were published earlier, which allowed for a scientific discussion on what is called a pre-print server. The results of the study have now been published in full in Nature.

The D614G variant carries a mutation in the spike protein which facilitates the binding of the virus to human cells. Researchers from the IVI and the laboratory of David E. Wentworth at the Centers for Disease Control and Prevention in Atlanta (United States) first demonstrated in cultures of human cells from the upper respiratory tract, as well as the nose, that the D614G variant binds more strongly and also replicates faster than the original virus. The increased replication of the D614G variant was also confirmed in vivo, in a new mouse model described for the first time in this study. These experiments were also carried out at the IVI in the group of Charaf Benarafa.

The new mutation clearly prevails

The spread of SARS-CoV-2 viruses may be better studied in other animals than in mice. Hamsters and ferrets are well established in infection research and are particularly suitable 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, the experimentally infected animals were rehoused with another healthy sentinel animal of the same species, to assess the transmission of the two variants in direct competition with each other. The experiment was repeated with six pairs of animals in total. In virtually all sentinel animals, the proportion of transmitted SARS-CoV-2 virus was overwhelmingly dominated by the D614G variant from the start. The differentiation of the variants was carried out using the latest sequencing technology and PCR techniques by Martin Beer’s team at the Friedrich Loeffler Institute, Federal Institute for Animal Health Research, Greifswald-Insel Riems (D). “Our study stands out because we were able to clearly discern the most efficient transmission of the mutated variant in direct comparison with the original variant,” explains Volker Thiel.

A fitness test for other mutations

This approach can even be used to test any single mutation or a specific combination of mutations that are present in a number of viral variants currently in circulation. The IVI is based on a cloning technique developed in Bern a year ago, in which the SARS-CoV-2 viruses can be reproduced exactly in the laboratory. The British virus, for example, is known to have not only one but often more than 14 mutations, eight of which occur in the spike protein. Thus, using the cloning technique, any number of variant mutations can be reproduced and used to compete with each other in established cell cultures and animal models. The results show how unique mutations affect the fitness and transmissibility of new variants. “Our testing strategy allows us to quickly examine why other newly emerging virus variants have become established,” 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.

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

More information:
Bin Zhou et al, change in SARS-CoV-2 peak D614G 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) retrieved on February 27, 2021 from

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