Journal
VIRUSES-BASEL
Volume 15, Issue 3, Pages -Publisher
MDPI
DOI: 10.3390/v15030611
Keywords
clinical isolates; variants; pathology; immune response; replication; SARS-CoV-2; beta coronavirus; next-generation sequencing; single nucleotide polymorphism; K18-hACE2 transgenic mice
Categories
Ask authors/readers for more resources
The closely related clinical isolates of SARS-CoV-2 exhibit phenotypic divergence and induce different immune responses. One variant shows faster viral replication and lower mortality rate, with unique immune responses. Lung histopathology reveals distinct phenotypes among the isolates.
The emergence and availability of closely related clinical isolates of SARS-CoV-2 offers a unique opportunity to identify novel nonsynonymous mutations that may impact phenotype. Global sequencing efforts show that SARS-CoV-2 variants have emerged and then been replaced since the beginning of the pandemic, yet we have limited information regarding the breadth of variant-specific host responses. Using primary cell cultures and the K18-hACE2 mouse, we investigated the replication, innate immune response, and pathology of closely related, clinical variants circulating during the first wave of the pandemic. Mathematical modeling of the lung viral replication of four clinical isolates showed a dichotomy between two B.1. isolates with significantly faster and slower infected cell clearance rates, respectively. While isolates induced several common immune host responses to infection, one B.1 isolate was unique in the promotion of eosinophil-associated proteins IL-5 and CCL11. Moreover, its mortality rate was significantly slower. Lung microscopic histopathology suggested further phenotypic divergence among the five isolates showing three distinct sets of phenotypes: (i) consolidation, alveolar hemorrhage, and inflammation, (ii) interstitial inflammation/septal thickening and peribronchiolar/perivascular lymphoid cells, and (iii) consolidation, alveolar involvement, and endothelial hypertrophy/margination. Together these findings show divergence in the phenotypic outcomes of these clinical isolates and reveal the potential importance of nonsynonymous mutations in nsp2 and ORF8.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available