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[Preprint]. 2021 Dec 29:rs.3.rs-1211792. [Version 1] doi: 10.21203/rs.3.rs-1211792/v1

Figure 2. B.1.1.529 is attenuated in wild-type and human ACE2-transgenic Syrian hamsters.

Figure 2

a, Weight change in uninfected age-matched Syrian hamsters (open grey circles, n = 4) or in hamsters inoculated intranasally with 105 PFU (n = 9) of B.1.1.529 (strain hCoV-19/Japan/NC928–2N/2021, blue circles), B.1.351 (Beta, HP01542), B.1.617.2 (Delta, strain hCoV-19/USA/WI-UW-5250/2021), B.1.621 (Mu, 80384), B.1.427 (Epsilon, VRLC009), B.1.526 (Iota, PV26425), C.37 (Lambda, SEC0506), or Wuhan-1 (black circles). b, Weight change in uninfected age-matched Syrian hamsters (open grey circles, n = 3) or in hamsters inoculated intranasally with 103 PFU of B.1.1.529 (strain hCoV-19/Japan/NC928–2N/2021, red circles, n = 4) or B.1.617.2 (black squares, n = 4). Data are mean ± SEM. c, Weight change in uninfected age-matched Syrian hamsters (open grey circles, n = 9) or in hamsters inoculated intranasally with 103 PFU of B.1.1.529 (strain hCoV-19/USA/WI-WSLH-221686/2021, red circles, n = 10) or WA1/2020 D614G (black triangles, n = 6). Data are mean ± SEM. (* P < 0.05, ** P < 0.01, *** P < 0.001 by two-way ANOVA with a Dunnett’s correction). d, Weight change in Syrian hamsters inoculated intranasally with 103 (red circles, n = 4), 104 (purple circles, n = 4), 105 (blue circles, n = 4), or 106 (green circles, n = 4) PFU of B.1.1.529 (strain hCoV19/EHC_C19_2811C) or 103 PFU of B.1.617.2 (black squares, n = 4). Data are mean ± SEM. e, Weight change in hamsters inoculated intranasally with 104 PFU of B.1.1.529 (strain hCoV19/EHC_C19_2811C, purple circles, n = 5) or WA1/2020 (black diamonds, n = 9). Data are mean ± SEM. f, Nasal wash and lung viral RNA load in wild-type Syrian hamsters inoculated with 103 PFU of WA1/2020 D614G (black triangles, n = 15) or B.1.1.529 (strain hCoV-19/USA/WI-WSLH-221686/2021, red circles, n = 15) (*** P < 0.001, * P < 0.05 by unpaired t-test). g, Nasal turbinates and lung virus titer in wild-type Syrian hamsters inoculated with 103 PFU of B.1.617.2 (strain hCoV-19/USA/WI-UW-5250/2021, black squares, n = 4) or B.1.1.529 (strain hCoV-19/Japan/NC928–2N/2021, red circles, n = 4) (* P < 0.05, ns = not significant; Mann Whitney U test). h, Nasal wash viral RNA load (TCID50 equivalents/mL) in wild-type Syrian hamsters inoculated with 104 PFU of WA1/2020 (black diamonds, n = 8) or B.1.1.529 (strain hCoV19/EHC_C19_2811C, purple circles, n = 3). i, Pulmonary function analysis in infected Syrian hamsters. Penh was measured by whole body plethysmography. Data are mean ± SEM. P values were calculated by using pairwise comparisons after a linear mixed model analysis (*** P < 0.001, ** P < 0.01, * P < 0.05). Asterisks indicate statistically significant differences between B.1.617.2-infected (n = 4) and B.1.1.529-infected (n = 4) or uninfected animals (n = 3). j, Representative micro-CT axial and coronal images of the lungs of mock-infected (n = 3) or B.1.617.2- (n = 4) and B.1.1.529-infected (n = 4) hamsters on 7 dpi. Lung abnormalities included multifocal nodules (black arrows), ground glass opacity (white arrowheads), and regions of lung consolidation (white arrows) that were peripheral, bilateral, and multilobar. Pneumomediastinum is indicated with white asterisks. k, CT score for uninfected hamsters (open grey circles, n = 3) or those inoculated with 103 PFU of B.1.617.2 (black squares, n = 4) or B.1.1.529 (strain hCoV-19/Japan/NC928–2N/2021, red circles, n = 4). l, Weight change in hACE2-transgenic Syrian hamsters inoculated intranasally with 103 PFU of HP-095 D614G (black triangles, n = 4) or B.1.1.529 (strain hCoV-19/USA/WI-WSLH-221686/2021, red circles, n = 4). m, Survival analysis of hACE2-transgenic Syrian hamsters after inoculation with 103 PFU of HP-095 D614G (black triangles, n = 4) or B.1.1.529 (strain hCoV-19/USA/WI-WSLH-221686/2021, red circles, n = 4) (* P < 0.05; log-rank test). n, Nasal turbinate and lung infectious virus titer by plaque assay at 3 and 5 dpi from hACE2-transgenic Syrian hamsters inoculated with 103 PFU of HP-095 D614G (black triangles) or B.1.1.529 (strain hCoV19/USA/WI-WSLH-221686/2021, red circles); n = 3 (3 dpi), n = 4 (5 dpi). The results in the Figure are from one (a, b, d-e, and g-n) or two to three independent (c, and f) experiments. Each symbol represents an individual animal. Dotted lines represent the limit of detection.