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Updated: Aug 12, 2025

Reverse Genetics to Engineer Positive-Sense RNA Virus Variants
Published on: June 9, 2022
Modeling nonsegmented negative-strand RNA virus (NNSV) transcription with ejective polymerase collisions and biased
Felipe-Andrés Piedra1, David Henke1, Anubama Rajan1
1Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, Unites States.
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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