SARS-CoV-2 spike-protein D614G mutation increases virion spike density and infectivity

• Published in: Nature communications Vol. 11; no. 1; pp. 6013 - 9
• Main Authors: Zhang, Lizhou, Jackson, Cody B., Mou, Huihui, Ojha, Amrita, Peng, Haiyong, Quinlan, Brian D., Rangarajan, Erumbi S., Pan, Andi, Vanderheiden, Abigail, Suthar, Mehul S., Li, Wenhui, Izard, Tina, Rader, Christoph, Farzan, Michael, Choe, Hyeryun
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 26.11.2020; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/106; 13/109; 13/31; 631/326/596; 631/326/596/4130; ACE2; Amino Acid Substitution; Angiotensin-converting enzyme 2; Angiotensin-Converting Enzyme 2 - metabolism; COVID-19 - epidemiology; COVID-19 - virology; HEK293 Cells; Humanities and Social Sciences; Humans; Infectivity; multidisciplinary; Mutation; Neutralization; Pandemics; Proteins; SARS-CoV-2 - genetics; SARS-CoV-2 - pathogenicity; Science; Science (multidisciplinary); Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus - genetics; Spike Glycoprotein, Coronavirus - metabolism; Spikes; Virion - metabolism; Virions; Virus Assembly - genetics; Virus Internalization; Virus-like particles
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-19808-4

SARS-CoV-2 variants with spike (S)-protein D614G mutations now predominate globally. We therefore compare the properties of the mutated S protein (S G614 ) with the original (S D614 ). We report here pseudoviruses carrying S G614 enter ACE2-expressing cells more efficiently than those with S D614 . This increased entry correlates with less S1-domain shedding and higher S-protein incorporation into the virion. Similar results are obtained with virus-like particles produced with SARS-CoV-2 M, N, E, and S proteins. However, D614G does not alter S-protein binding to ACE2 or neutralization sensitivity of pseudoviruses. Thus, D614G may increase infectivity by assembling more functional S protein into the virion. SARS-CoV-2 variants with spike (S)-protein D614G mutations currently predominate globally. Here, Zhang et al. hypothesize that D614G variant may increase infectivity by increasing S protein abundance on the virion since pseudoviruses carrying S-G614 incorporate higher amounts of S protein and enter cells more efficiently than those carrying S-D614.