Norovirus genomes detected from the Guillain-Barré syndrome (GBS) cases in a community outbreak in Pune, India, 2025.

Background: In 2025, Pune, India, witnessed an unprecedented surge in Guillain-Barré Syndrome (GBS) cases, raising urgent public health concerns. GBS, a rare neurological condition often linked to infections, demanded immediate epidemiological and molecular scrutiny. Evidence from earlier studies points to infectious agents like Campylobacter jejuni, cytomegalovirus, and enteric viruses as common triggers. Environmental conditions and regional pathogen variations were considered potential contributors to the outbreak. To uncover the cause, a broad molecular screening was initiated to detect any known or emerging infectious agents.

Methods: A comprehensive molecular screening was conducted for 19 pathogens, including established GBS-linked and enteric pathogens. Advanced genomic techniques, including phylogenetic and mutation analysis, were employed to characterize the detected pathogens.

Findings: Two major pathogens, Campylobacter jejuni and Norovirus, were identified by using molecular methods. Whole-genome sequencing of 12 representative strains using a genotyping tool revealed their classification into genogroup II within three major genotypes: GII.16[P16] (n=9, GBS-associated), GII.17[P17] (n=2), and GII.4 Sydney[P16] (n=1). Phylogenetic analysis based on VP1 and RdRp genes confirmed genotyping and revealed that all norovirus strains from GBS patients clustered within a potential distinct Indian sub-lineage, closely related to strains reported from Russia, USA and Germany, suggesting possible global dissemination. The GII.17 strains belonged to the globally dominant Romania-2021-like lineage, while the GII.4 strain clustered with the pandemic Sydney[P16] variants. Mutation analysis revealed genotype-specific patterns. GII.17 strains had the highest number of non-synonymous mutations (>160), mostly in ORF1 (RdRp; RNA-dependent RNA polymerase), suggesting replication adaptation. In contrast, GBS-associated GII.16 strains showed increased mutations in ORF2 (VP1; major capsid protein), likely driven by immune selection pressures.

Interpretation: These findings highlight the importance of genomic surveillance to identify emerging norovirus lineages and their potential clinical significance. Continued monitoring is vital to understand norovirus evolution and its possible connection to GBS.