Modeling Nonsegmented Negative-Strand RNA Virus (Nnsv) Transcription With Ejective Polymerase Collisions and Biased Diffusion

Authors

Felipe-Andrés Piedra
David Henke
Anubama Rajan
Donna M Muzny
Harsha Doddapaneni
Vipin K Menon
Kristi L Hoffman
Matthew C Ross
Sara J Javornik Cregeen
Ginger Metcalf
Richard A Gibbs
Joseph F Petrosino
Vasanthi Avadhanula
Pedro A Piedra

Publication Date

1-1-2022

Journal

Frontiers in Molecular Biosciences

DOI

10.3389/fmolb.2022.1095193

PMID

36699700

PMCID

PMC9868645

PubMedCentral® Posted Date

1-9-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

RNA viral genome, transcriptional regulation, biased diffusion, polymerase collisions, viral gene expression

Abstract

Infections by non-segmented negative-strand RNA viruses (NNSV) are widely thought to entail gradient gene expression from the well-established existence of a single promoter at the 3' end of the viral genome and the assumption of constant transcriptional attenuation between genes. But multiple recent studies show viral mRNA levels in infections by respiratory syncytial virus (RSV), a major human pathogen and member of NNSV, that are inconsistent with a simple gradient. Here we integrate known and newly predicted phenomena into a biophysically reasonable model of NNSV transcription. Our model succeeds in capturing published observations of respiratory syncytial virus and vesicular stomatitis virus (VSV) mRNA levels. We therefore propose a novel understanding of NNSV transcription based on the possibility of ejective polymerase-polymerase collisions and, in the case of RSV, biased polymerase diffusion.

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