Chikungunya Virus RNA Secondary Structures Impact Defective Viral Genomes Production

• DOI: 10.20944/preprints202407.1212.v1
• Publication Date: 2024-07-16T12:06:49Z
• Authors: Laura I LEVI; Emily A Madden; Jeremy Boussier; Diana Erazo; Wes Sanders; Thomas Valley; Veronika Bernhaue...; Nathaniel J. J Mo...; Mark T Heise; Marco Vignuzzi
• Keywords: Primer extension; RNA virus; Nucleic acid structure

Chikungunya virus (CHIKV) is a mosquito borne RNA that poses an emerging threat to humans. As other viruses, CHIKV encodes error-prone polymerase which, in addition full-length genomes, gives rise truncated, non-functional genomes coined defective viral (DVGs). DVGs have been intensively studied the context of therapy, as they can inhibit replication and dissemination their hosts. In this work, we interrogate influence secondary structures on production DVGs. We experimentally map genome using selective 2′-hydroxyl acylation analyzed by primer extension mutational profiling (SHAPE-MaP), which couples chemical labelling with next-generation sequencing. correlate inferred structure preferred deletion sites document increased probability DVG generation truncations at unpaired nucleotides within structure. then generated mutant bearing synonymous changes nucleotide level disrupt existing (CHIKV-D2S). show CHIKV-D2S presents altered compared wild-type virus, correlating its change obtained SHAPE-MaP. Our work thus demonstrates impacts during replication.