SARS-CoV-2 spike D614G variant exhibits highly efficient replication and transmission in hamsters

Abstract

SARS-CoV-2 causes disease varying in severity from asymptomatic infections to severe respiratory distress and death in humans. The viral factors which determine transmissibility and pathogenicity are not yet clearly characterized. We used the hamster infection model to compare the replication ability and pathogenicity of five SARS-CoV-2 strains isolated from early cases originating in Wuhan, China, in February, and infected individuals returning from Europe and elsewhere in March 2020. The HK-13 and HK-95 isolates showed distinct pathogenicity in hamsters, with higher virus titers and more severe pathological changes in the lungs observed compared to other isolates. HK-95 contains a D614G substitution in the spike protein and demonstrated higher viral gene expression and transmission efficiency in hamsters. Intra-host diversity analysis revealed that further quasi species were generated during hamster infections, indicating that strain-specific adaptive mutants with advantages in replication and transmission will continue to arise and dominate subsequent waves of SARS-CoV-2 dissemination.

Rapid Spread of Mutant Alleles in Worldwide SARS-CoV-2 Strains Revealed by Genome-Wide Single Nucleotide Polymorphism and Variation Analysis

“…Experiments on virus by other groups confirmed those feature of LG_1 ( Korber et al. 2020 ; Mok et al. 2020 ).…”

“…Until now, parts of our prediction are supported by virology experiments using hamster as animal model, which focused on the clinical influence of SNP_23403, LG_1 (D614G). This experiment indicate that D614G SARS-CoV-2 mutant strains cause more severe pathological changes in the lung tissues when compared with unmutated isolates ( Mok et al. 2020 ).…”

Viral MicroRNAs Encoded by Nucleocapsid Gene of SARS-CoV-2 Are Detected during Infection, and Targeting Metabolic Pathways in Host Cells

“…SARS-CoV-2 clones, HK-95 (PANGO lineage B.43; accession number MT835143) and HK-405 (PANGO lineage B.1.36.27; accession number MW856793), were isolated from the nasopharyngeal aspirate of sequence-confirmed COVID-19 patients in Hong Kong [ 22 , 23 ]. The viral isolates were grown through Vero E6 cells (CRL-1586, ATCC) [ 22 , 23 ] in Dulbecco’s modified Eagle’s medium (DMEM) (Thermo Fisher Scientific, Waltham, MA, USA) supplemented with 10% fetal bovine serum (FBS) (Thermo Fisher Scientific, Waltham, MA, USA), 100 units/mL penicillin and 100 µg/mL streptomycin (1% P/S) (Thermo Fisher Scientific, Waltham, MA, USA). All experiments involving live SARS-CoV-2 were done in a Biosafety Level 3 (BSL-3) facility with strict adherence to the standard operating procedures.…”

Functional importance of the D614G mutation in the SARS-CoV-2 spike protein

“…Mok et al compared the infectivity in hamsters of three live SARS-CoV-2 isolates, two with S(D614) (HK-8 and HK-13) and one with S(G614) (HK-95). Significantly higher viral titers were observed in the lungs and nasal turbinates of naïve hamsters co-housed with HK-95-infected hamsters than in those co-housed with HK-8- or HK-13-infected hamsters [ 46 ]. The findings support the hypothesis that the D614G variant of S protein promotes transmissibility of the virus in mammals.…”