Notes from Dr. David Montefiori
Reflections on our COVID-19 study in early 2020
TrackingChanges in SARS-CoV-2 Spike: Evidence that D614G Increases Infectivity of theCOVID-19 Virus. Korber B, Fischer WM, Gnanakaran S, Yoon H, Theiler J, Abfalterer W, Hengartner N, Giorgi EE, Bhattacharya T, Foley B, Hastie KM, Parker MD, Partridge DG, Evans CM, Freeman TM, de Silva TI; Sheffield COVID-19 Genomics Group; McDanal C, Perez LG, Tang H, Moon-Walker A, Whelan SP, LaBranche CC, Saphire EO, Montefiori DC. Cell 182(4):812-827 2020
Dr. Bette Korber and I teamed up very early in the COVID-19 pandemic out of concern the SARS-CoV-2 virus would evolve to adapt to its new human host in ways that would make the virus more contagious as a means of ensuring its survival in the human population. In fact, this is exactly what happened. By February 2020, the virus acquired a single mutation called “D614G” in its spike protein that stood out among all of the other scattered mutations that were appearing because it was being sampled with ever-increasing frequency. Bette’s computational analysis of the rate of spread of this new D614G variant over time strongly indicated it had a fitness advantage for transmission, quickly overtaking the ancestral Wuhan-1 form of the virus wherever it appeared in the world. The D614G variant had almost completely replaced the ancestral strain everywhere in the world by March/April 2020, a time when government and public health officials were encouraging people to safeguard against infection by taking seriously their recommendations for social distancing, avoiding crowds, hand washing and mask wearing.
Our message to the public at this time was that the new D614G variant, with its heightened ability to spread, is even more reason to take these recommendations seriously. However, many scientists were skeptical and argued that the rapid spread of the D614G variant was due to factors unrelated to transmission fitness. What was missing was laboratory evidence to support Bette’s computational findings. In the Montefiori lab, we quickly set out to determine whether the D614G mutation made the virus more infectious in laboratory experiments. Our experimental results showed the D614G mutation increased the infectivity of the virus by 3-4-fold in laboratory cultures of human cells. A mutual colleague, Dr. Erica Ollmann Saphire, performed similar laboratory experiments and came to the same conclusion. Subsequent studies by others showed the D614G mutation made the virus more contagious in live animal experiments and provided a biological mechanism to account for the increased transmission fitness. The skeptics finally came around to accepting Bette’s computational methods, which continue to be used to identify newly emerging variants with mutations that impart a transmission advantage. Altogether this work on the D614G variant foretold the ability of SARS-CoV-2 to evolve and give rise to later variants of concern that earned a Greek letter.
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