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bioRxiv · 10.1101/2024.07.07.602380

RNA genome expansion up to 64 kb in nidoviruses is host constrained and associated with new modes of replicase expression

Neuman, B. W.·Smart, A.·Vaas, J.·Bartenschlager, R.·Seitz, S.·Gorbalenya, A. E.·Caliskan, N. E.·Lauber, C.
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Abstract

Positive-strand RNA viruses of the order Nidovirales with genomes larger than [~]20 kb, including the largest known 36.7 kb RNA genome in vertebrate viruses, encode a proofreading exoribonuclease (ExoN). Here, we assemble 76 genome sequences of invertebrate nidoviruses from >500.000 published transcriptome experiments and triple the number of known nidoviruses with >36 kb genomes, including the largest known 64 kb RNA genome. We classify multi-cistronic ExoN-encoding nidoviruses into five groups, according to canonical and non-canonical modes of viral polymerase expression by ribosomes and genome segmentation. The largest group employing the canonical mode comprises invertebrate and vertebrate nidoviruses, including coronaviruses, with genomes ranging from 20-to-36 kb. Four groups with non-canonical expression modes include giant invertebrate nidoviruses with 31-to-64 kb genomes, some of which utilize dual ribosomal frameshifting that we validate experimentally. Thus, expansion of giant RNA virus genomes, the vertebrate/invertebrate host division, and the control of viral replicase expression are interconnected.

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Neuman, B. W., Smart, A., Vaas, J., Bartenschlager, R., Seitz, S., Gorbalenya, A. E., Caliskan, N. E., Lauber, C.. 2024-07-07. RNA genome expansion up to 64 kb in nidoviruses is host constrained and associated with new modes of replicase expression. https://doi.org/10.1101/2024.07.07.602380

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