Insertion of a short non-viral sequence in the 3′ noncoding region of the hemagglutinin-neuraminidase increases mumps virus neurovirulence

Abstract

The mumps virus is a promising candidate as a vaccine vector or oncolytic therapy agent. However, its neurotropic nature, driven by molecular mechanisms that remain unclear, poses a significant obstacle to its development for these applications. This study utilizes recombinant mumps virus carrying the enhanced green fluorescent protein gene (EGFP) and two additional viruses containing, alongside EGFP, unique non-viral, non-coding 84-nucleotide inserts in the 3′ non-coding region (NCR) of the hemagglutinin-neuraminidase (HN) gene. We observed a significant increase in neurovirulence for both viruses containing inserts in the 3’ NCR of HN. The insert in HN 3′ NCR provided a replicative advantage in the brains of newborn rats and rat brain-derived cell cultures. While the viruses were able to infect rat neurons, infection of astrocytes was completely inhibited. Additionally, in infected rat brain and rat brain-derived cell cultures we detected induction of RANTES. We observed no correlation in the extent of neuronal apoptosis or the induction of pro-inflammatory cytokines between viruses with or without the HN 3′ NCR insert.