Clinico-genetic characterisation of an encephalitic Dengue virus 4 associated with multi-organ involvement

Neurological manifestations due to Dengue virus (DENV) infection are atypical and uncommon. Genomic information of clinically characterised, neurotrophic DENV in humans is extremely limited albeit their importance in deciphering the pathogenicity is substantial. Here, we report a rare case of fatal DENV-4 infection complicated with encephalitis and multi-organ failure. The clinical presentation was unusual due to its rapid onset of encephalitis despite a very low virus titre. Full genomes of serum and CSF-derived viruses shared 99.99% similarity, indicating the virus dissemination across blood-brain barrier. Even though virus genomes did not reveal any of the neurotrophic substitutions of DENV documented so far, case isolates possessed a combination of 8 novel amino acid alterations, predominantly distributed in non-structural genes of DENV-4.