Examining impact of a point mutation in SARS-Cov-2 spike on virus transmission and pathogenicity

November 12, 2020

The current dominant variant of SARS-CoV-2, containing a D614G substitution in the spike protein, appears to have evolved to enhance transmissibility, according to a new study in human cells and animal models. Its results address concerns that have been raised about how this emergent mutation could enhance transmissibility, antigenicity, and/or pathogenesis, with implications for therapies under development. Pandemic spread of a virus in naïve populations can select for mutations that alter pathogenesis, virulence and/or transmissibility. Mutations could challenge the development of vaccine and therapeutic antibodies. Today, the ancestral form of SARS-CoV-2 that emerged from China has been largely replaced by strains containing a D614G mutation in the virus spike. While this spike substitution is prevalent in global SARS-CoV-2 strains, its effects on viral pathogenesis and transmissibility remain unclear. To better understand them, Yixuan Hou, Ralph Baric and colleagues engineered a SARS-CoV-2 variant containing this substitution and used it to compare, in a series of experiments in human cells and animal models, the characteristics of the new variant against the ancestral form. Compared to the ancestral virus, the variant showed an enhanced ability to infect upper airway epithelial cells and to replicate, the work in human cells showed. In mice and Syrian hamsters engineered to exhibit human cell features, both viruses resulted in similar viral titers in respiratory tissues; the hamsters displayed some increased weight loss, which suggests a marginal impact on disease outcomes from the variant, the authors say, but overall, the results suggest the D614G substitution doesn't significantly enhance virus pathogenesis. The variant did transmit significantly faster in hamsters, the authors say. Thus, they say, the virus seems to have evolved not for greater pathogenicity, but for greater transmissibility in humans. They also evaluated the neutralization properties of convalescent human serum samples and SARS-CoV-2 neutralizing monoclonal antibodies on the variant and the ancestral form, finding no significant difference. These data suggest that the current vaccine approaches targeted against the ancestral spike protein should be effective against the D614G strains, the authors say. They note several limitations of their study and emphasize:" It is clearly important to monitor and identify the emergence of new variants of SARS-CoV-2."

American Association for the Advancement of Science

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