Research out in the journal Cell shows that a specific
change in the SARS-CoV-2 coronavirus virus genome, previously associated with
increased viral transmission and the spread of COVID-19, is more infectious in
cell culture. The variant in question, D614G, makes a small but effective change
in the virus’s ‘Spike’ protein, which the virus uses to enter human cells.
Bette Korber, a theoretical biologist at Los Alamos
National Laboratory and lead author of the study, noted, “The D614G variant
first came to our attention in early April, as we had observed a strikingly
repetitive pattern. All over the world, even when local epidemics had many
cases of the original form circulating, soon after the D614G variant was
introduced into a region it became the prevalent form.”
Geographic information from samples from the GISAID
COVID-19 viral sequence database enabled tracking of this highly recurrent
pattern, a shift in the viral population from the original form to the D614G
variant. This occurred at every geographic level: country, subcountry, county,
and city.
Two independent lines of
experimental evidence that support these initial results are included in
today’s paper. These additional experiments, led by Professor Erica Ollmann
Saphire, Ph.D., at the La Jolla Institute, and by Professor David Montefiori,
Ph.D., at Duke University, showed that the D614G change increases the virus’s
infectivity in the laboratory. These new experiments, as well as more extensive
sequence and clinical data and improved statistical models, are presented in
the Cell paper.
More in vivo work remains to be done to determine the full implications of the
change.
The SARS-CoV-2 virus has a low mutation rate overall
(much lower than the viruses that cause influenza and HIV-AIDS). The D614G
variant appears as part of a set of four linked mutations that appear to have
arisen once and then moved together around the world as a consistent set of
variations.
“It’s remarkable to me,” commented Will Fischer of Los
Alamos, an author on the study, “both that this increase in infectivity was
detected by careful observation of sequence data alone, and that our
experimental colleagues could confirm it with live virus in such a short time.”
Fortunately, “the clinical data in this paper from
Sheffield showed that even though patients with the new G virus carried more
copies of the virus than patients infected with D, there wasn’t a corresponding
increase in the severity of illness,” said Saphire, who leads the Gates
Foundation-supported Coronavirus Immunotherapy Consortium (CoVIC).
Korber noted, “These findings suggest that the newer
form of the virus may be even more readily transmitted than the original form —
whether or not that conclusion is ultimately confirmed, it highlights the value
of what were already good ideas: to wear masks and to maintain social
distancing.”
Research partners from Los Alamos National Laboratory,
Duke University, and the University of Sheffield initially published work on
this analysis on the bioRxiv site in an April 2020 preprint. That work also
included observations of COVID-19 patients from Sheffield that suggested an
association of the D614G variant with higher viral loads in the upper
respiratory tract.
“It is possible to track SARS-CoV-2 evolution globally
because researchers worldwide are rapidly making their viral sequence data
available through the GISAID viral sequence database,” Korber said. Currently
tens of thousands of sequences are available through this project, and this
enabled Korber and the research team to identify the emergence of the D614G
variant.
GISAID was established to encourage collaboration
among influenza researchers, but early in the epidemic the consortium
established a SARS-CoV-2 database, which soon became the de facto standard for
sharing outbreak sequences among researchers worldwide.
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