PLOS Biology · 15 authors, 5 centres
This summary was generated by AI from a single paper. It has not been reviewed by a clinician and is not clinical advice. Verify against the source before acting on it.
Using reverse genetics and replicon systems for MLB1 and MLB2 astroviruses, the authors identified dispensable regions in the 3′ capsid-coding region whose deletion imbalances RNA synthesis and strongly attenuates virus replication in iPSC-derived neuronal cultures. This approach highlights potential attenuation strategies for neurotropic astroviruses with implications for vaccine development.
The authors developed reverse genetics and replicon systems for MLB1 and MLB2 human astroviruses, enabling generation and characterization of recombinant deletion mutants. Using virus evolution approaches, dispensable regions were identified in the 3′ end of the capsid-coding region. Recombinant truncated MLB viruses exhibited imbalanced RNA synthesis and strong attenuation in iPSC-derived neuronal cultures, while being well tolerated in the highly susceptible Huh7.5.1 hepatocarcinoma cell line. MLB1 deletion mutants showed enhanced genome replication but lower infectious particle release in neurons, whereas MLB2 attenuation by a small 5-nucleotide out-of-frame deletion resulted in 10-fold decreased RNA levels in neuronal infection. MLB2 demonstrated remarkable genomic stability across serial passages compared with MLB1. The study is limited by the absence of an animal model for human astroviruses and relies entirely on in vitro cell culture systems. These findings represent the first demonstration of an attenuation strategy for neurotropic astroviruses.
