La Crosse virus (LACV) is a primary cause of pediatric arboviral encephalitis in the United States, particularly affecting children aged 16 years or younger, and this age-related susceptibility extends to murine models, where weanling mice (3 weeks old) succumb to LACV infection, while adults (≥6 weeks old) demonstrate resistance, and this study by Bobby Brooke Herrera’s Lab at the Rutgers Global Health Institute investigated the roles of neutralizing antibodies, cytokines, and chemokines in weanling and adult mice following LACV infection. They found:
- Age-related susceptibility to LACV infection is maintained even at higher infectious doses, with weanling mice exhibiting earlier disease onset and higher peripheral viremia compared to adult mice.
- Despite early production of neutralizing antibodies in weanling mice, they failed to correlate with viral clearance, suggesting nAbs may not be the sole determinant of protection.
- Adult mice exhibited significantly elevated levels of Th1 cytokines, chemokines, and Th9/Th17/Th22/Treg cytokines compared to weanling mice, which had higher Th2 cytokines, correlating with symptom onset.
The study contributes to a deeper understanding of immune responses to neurotropic bunyavirus infections and offers insights into potential therapeutic targets and biomarkers for disease management, while future research should focus on elucidating the underlying mechanisms driving age-related susceptibility, further characterizing the immune response dynamics, and exploring therapeutic interventions to mitigate the neurological complications associated with LACV infection.
Alatrash R, Vaidya V, Herrera BB. Age-specific dynamics of neutralizing antibodies, cytokines, and chemokines in response to La Crosse virus infection in mice. J Virol. 2024 Dec 17;98(12):e0176224. doi: 10.1128/jvi.01762-24. Epub 2024 Nov 5. PMID: 39498968. https://journals.asm.org/doi/10.1128/jvi.01762-24
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