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The Spike D614G mutation increases SARS-CoV-2 infection of multiple human cell types

Zharko Daniloski1,2, Tristan X Jordan3, Juliana K Ilmain4

  • 1New York Genome Center, New York, United States.

Elife
|February 11, 2021
PubMed

Insights

The SARS-CoV-2 D614G Spike protein variant enhances viral transduction and infectivity in human cells. This variant shows increased resistance to proteolytic cleavage, contributing to its prevalence.

Area of Science:

  • Virology
  • Molecular Biology
  • Genetics

Background:

  • A novel SARS-CoV-2 variant with a D614G mutation in the Spike protein has rapidly become dominant.
  • Linkage disequilibrium with an ORF1b protein variant (P314L) complicates understanding the D614G mutation's functional impact.

Purpose of the Study:

  • To investigate the functional significance of the SARS-CoV-2 Spike D614G mutation.
  • To determine the effect of the D614G variant on viral transduction and infectivity.

Main Methods:

  • Site-directed mutagenesis was used to introduce the D614G variant into the Spike protein.
  • Lentiviral particles pseudotyped with wild-type and D614G Spike variants were used to transduce various human cell lines.
  • SARS-CoV-2 virus was complemented with the D614G Spike variant for infectivity assays.
  • ACE2 receptor binding and proteolytic cleavage resistance were assessed.

Main Results:

  • Pseudotyped lentiviral particles with Spike D614G showed significantly increased transduction efficiency across multiple human cell lines (1.3- to 7.7-fold increase).
  • SARS-CoV-2 virus complemented with Spike D614G exhibited enhanced infectivity in human cells.
  • The D614G Spike variant demonstrated increased resistance to proteolytic cleavage compared to the wild-type D614 variant.
  • Minimal difference in ACE2 receptor binding was observed between D614 and G614 Spike variants.

Conclusions:

  • The Spike D614G mutation enhances SARS-CoV-2 infectivity and cell transduction.
  • Increased resistance to proteolytic cleavage is a potential mechanism driving the enhanced infectivity of the D614G variant.
  • These findings provide functional insights into the rapid global spread of the D614G SARS-CoV-2 variant.
Keywords:
COVID-19D614GSARS-CoV-2Spikecoronavirusepidemiologyglobal healthhumaninfectious diseasemicrobiologyvirus

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