RT Journal Article
SR Electronic
T1 Subgenomic RNAs as molecular indicators of asymptomatic SARS-CoV-2 infection
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.02.06.430041
DO 10.1101/2021.02.06.430041
A1 Chee Hong Wong
A1 Chew Yee Ngan
A1 Rachel L. Goldfeder
A1 Jennifer Idol
A1 Chris Kuhlberg
A1 Rahul Maurya
A1 Kevin Kelly
A1 Gregory Omerza
A1 Nicholas Renzette
A1 Francine De Abreu
A1 Lei Li
A1 Frederick A. Browne
A1 Edison T. Liu
A1 Chia-Lin Wei
YR 2021
UL http://biorxiv.org/content/early/2021/02/06/2021.02.06.430041.abstract
AB In coronaviridae such as SARS-CoV-2, subgenomic RNAs (sgRNA) are replicative intermediates, therefore, their abundance and structures could infer viral replication activity and severity of host infection. Here, we systematically characterized the sgRNA expression and their structural variation in 81 clinical specimens collected from symptomatic and asymptomatic individuals with a goal of assessing viral genomic signatures of disease severity. We demonstrated the highly coordinated and consistent expression of sgRNAs from individuals with robust infections that results in symptoms, and found their expression is significantly repressed in the asymptomatic infections, indicating that the ratio of sgRNAs to genomic RNA (sgRNA/gRNA) is highly correlated with the severity of the disease. Using long read sequencing technologies to characterize full-length sgRNA structures, we also observed widespread deletions in viral RNAs, and identified unique sets of deletions preferentially found primarily in symptomatic individuals, with many likely to confer changes in SARS-CoV-2 virulence and host responses. Furthermore, based on the sgRNA structures, the frequently occurred structural variants in SARS-CoV-2 genomes serves as a mechanism to further induce SARS-CoV-2 proteome complexity. Taken together, our results show that differential sgRNA expression and structural mutational burden both appear to be correlated with the clinical severity of SARS-CoV-2 infection. Longitudinally monitoring sgRNA expression and structural diversity could further guide treatment responses, testing strategies, and vaccine development.Competing Interest StatementCLW, CHW and CYN are co-inventors on a patent application submitted by The Jackson Laboratory entitled "Subgenomic RNAs for Evaluating Viral Infection". The other authors declare no conflict of interest.