We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Dysregulated TGF-β Production Underlies the Age-Related Vulnerability to Chikungunya Virus.
- Authors
Uhrlaub, Jennifer L.; Pulko, Vesna; DeFilippis, Victor R.; Broeckel, Rebecca; Streblow, Daniel N.; Coleman, Gary D.; Park, Byung S.; Lindo, John F.; Vickers, Ivan; Anzinger, Joshua J.; Nikolich-Žugich, Janko
- Abstract
Chikungunya virus (CHIKV) is a re-emerging global pathogen with pandemic potential, which causes fever, rash and debilitating arthralgia. Older adults over 65 years are particularly susceptible to severe and chronic CHIKV disease (CHIKVD), accounting for >90% of all CHIKV-related deaths. There are currently no approved vaccines or antiviral treatments available to limit chronic CHIKVD. Here we show that in old mice excessive, dysregulated TGFβ production during acute infection leads to a reduced immune response and subsequent chronic disease. Humans suffering from CHIKV infection also exhibited high TGFβ levels and a pronounced age-related defect in neutralizing anti-CHIKV antibody production. In vivo reduction of TGFβ levels minimized acute joint swelling, restored neutralizing antibody production and diminished chronic joint pathology in old mice. This study identifies increased and dysregulated TGFβ secretion as one key mechanism contributing to the age-related loss of protective anti-CHIKV-immunity leading to chronic CHIKVD.
- Subjects
CHIKUNGUNYA virus; FEBRILE neutropenia; OSTEOARTHRITIS; ANTIVIRAL agents; NONSTEROIDAL anti-inflammatory agents
- Publication
PLoS Pathogens, 2016, Vol 12, Issue 10, p1
- ISSN
1553-7366
- Publication type
Article
- DOI
10.1371/journal.ppat.1005891