The hidden diversity: Replication-strand asymmetry shapes short-term nucleotide and structural variation in an RNA virus
- 1I2SysBio-CSIC
Abstract
Orsay virus (OrV), a positive-sense RNA virus infecting Caenorhabditis elegans, establishes latent infections with minimal impact on host fitness. Using strand-specific RNA-seq across twelve time points spanning larval development, we characterized OrV replication dynamics and short-term evolutionary patterns. Viral accumulation followed four distinct phases and exhibited strong strand asymmetry, consistent with a predominance of the stamping-machine replication mechanism. Diversity analyses revealed that negative-strand genomes harbor more mutations than positive strands, with hotspots concentrated in the replicase C-terminal tail and structural protein regions. Many negative-strand variants failed to propagate to positive strands, suggesting within-cell constraints or purifying selection at the RNA level. We also report the first evidence of non-standard viral genomes in OrV, dominated by deletions in RNA2, including a recurrent large deletion that may function as a subgenomic RNA encoding a shorter version of the {delta} protein. These findings highlight replication asymmetry, strand-specific mutational filtering, and pervasive non-standard genomes as key features shaping OrV evolution during a primary infection.
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BibTeX
@misc{olmouceda2026hidden,
title = {{The hidden diversity: Replication-strand asymmetry shapes short-term nucleotide and structural variation in an RNA virus}},
author = {M. J. Olmo-Uceda and D. Herek and V. G. Castiglioni and S. F. Elena},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.04.749430},
url = {https://www.biorxiv.org/content/10.64898/2026.09.04.749430v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - The hidden diversity: Replication-strand asymmetry shapes short-term nucleotide and structural variation in an RNA virus
AU - M. J. Olmo-Uceda
AU - D. Herek
AU - V. G. Castiglioni
AU - S. F. Elena
PY - 2026
DA - 2026/09/04
PB - bioRxiv
DO - 10.64898/2026.09.04.749430
UR - https://www.biorxiv.org/content/10.64898/2026.09.04.749430v1
AB - Orsay virus (OrV), a positive-sense RNA virus infecting Caenorhabditis elegans, establishes latent infections with minimal impact on host fitness. Using strand-specific RNA-seq across twelve time points spanning larval development, we characterized OrV replication dynamics and short-term evolutionary patterns. Viral accumulation followed four distinct phases and exhibited strong strand asymmetry, consistent with a predominance of the stamping-machine replication mechanism. Diversity analyses revealed that negative-strand genomes harbor more mutations than positive strands, with hotspots concentrated in the replicase C-terminal tail and structural protein regions. Many negative-strand variants failed to propagate to positive strands, suggesting within-cell constraints or purifying selection at the RNA level. We also report the first evidence of non-standard viral genomes in OrV, dominated by deletions in RNA2, including a recurrent large deletion that may function as a subgenomic RNA encoding a shorter version of the {delta} protein. These findings highlight replication asymmetry, strand-specific mutational filtering, and pervasive non-standard genomes as key features shaping OrV evolution during a primary infection.
ER -