Immunodominant structural proteins Gc and N drive T cell-mediated protection against La Crosse virus
Year: 2025
Type: article
Abstract: SUMMARY La Crosse virus (LACV) is a major cause of pediatric encephalitis in the U.S., primarily affecting children under 16 years. Despite severe morbidity and potential mortality risks, no vaccines or antivirals exist. Murine models recapitulate human susceptibility patterns, with weanling mice (3 weeks old) succumbing to disease while adults (≥8 weeks old) exhibit resistance. We characterized the T cell responses underlying this difference. Adult mice mounted robust CD4 + and CD8 + T cell responses by 6 days post-infection (dpi), with sustained IFN-γ, granzyme B, IL-2, and TNF-α production. These T cells expanded significantly and exhibited in vivo cytotoxicity against cells pulsed with LACV glycoprotein (Gc) and nucleocapsid (N) antigens. In contrast, weanlings showed weak T cell responses and 100% mortality by 7 dpi. Immunization with LFn-LACV-Gc and -N improved T cell cytotoxicity and survival in weanlings, highlighting their potential as vaccines. These findings inform strategies to mitigate LACV-induced encephalitis in children.
Source: iScience
Authors: Reem Alatrash, Bobby Brooke Herrera
Institution: Rutgers, The State University of New Jersey
Language: English
Topic: Viral Infections and Vectors
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,240
Award: G8774642988
OpenAlex ID: W4413289977
