In Depth Viral Diversity Analysis in Atypical Neurological and Neonatal Chikungunya Infections in Rio de Janeiro,...

Area of Science:

• Virology
• Genetics
• Pathogenesis

Background:

• Chikungunya virus (CHIKV), an arbovirus transmitted by Aedes mosquitoes, typically causes self-limiting arthralgia.
• Since 2013, CHIKV has shown atypical presentations, including severe neuropathies and neonatal infections via vertical transmission.
• The underlying pathophysiological mechanisms of these severe CHIKV manifestations remain unclear, though intrahost genetic diversity is implicated.

Purpose of the Study:

• To investigate the intrahost genetic diversity of CHIKV in patients with neurological disease and in cases of vertical transmission.
• To identify potential viral variants associated with atypical CHIKV presentations and transmission routes.

Main Methods:

• Analysis of CHIKV intrahost genetic diversity in serum samples from patients with neurological manifestations.
• Analysis of CHIKV intrahost genetic diversity in mothers and newborns from intrapartum vertical transmission cases.
• In silico analysis of viral genetic patterns.

Main Results:

• No significant differences in overall genetic variability were found between groups.
• Newborn and cerebrospinal fluid (CSF) samples exhibited distinct intrahost mutant compositions compared to maternal/patient serum.
• A higher proportion of defective CHIKV variants (insertions/deletions, stop codons) was observed in CSF and maternal samples, primarily in non-structural genes.

Conclusions:

• Distinct viral compositions in CSF and newborn samples suggest selective bottlenecks during placental/BBB transmission.
• Defective viral genomes in atypical CHIKV cases warrant further investigation for their role in disease severity.
• No non-conservative mutations were identified that clearly explain the pathophysiology of atypical CHIKV presentations.