T cells protect against hepatitis A virus infection and limit infection-induced liver injury

• DOI: 10.1016/j.jhep.2021.07.019
• Publication Date: 2021-07-29T02:08:54Z
• Authors: Ichiro Misumi; Joseph E. Mitchell; Makayla M. Lund; John M. Cullen; Stanley M. Lemon; Jason K. Whitmire
• Keywords: Pathogenesis; Liver disease; Viral Hepatitis

•T cells protect against HAV-mediated liver injury and can be targeted to improve health.•Ifnar1-/- mice are permissive for HAV generate HAV-specific T within the during infection.•HAV replication was enhanced disease exacerbated when were depleted of CD4+ or CD8+ cells.•Peptide vaccination increased virus-specific cell frequencies reduced viral RNA injury. Background & AimsHepatitis A virus (HAV) is a common cause enterically transmitted hepatitis. In non-immune individuals, infection results in typically transient but occasionally fulminant fatal inflammatory Virus-specific peak damage at its zenith, leading prevalent notion that exacerbate disease, as suspected other hepatotropic infections. However, overall contribution control pathogenesis hepatitis unclear has been impeded by historic lack small animal models.MethodsIfnar1-/- highly develop recapitulates many features A. Using this model, we identified epitope mapping, then used tetramers functional assays quantify multiple times after infection. We assessed relationships between frequency, amounts, pathogenesis.ResultsA large population accumulated livers Ifnar1-/- first 1-2 weeks persisted over time. cells. Conversely, immunization with peptide vaccine liver, abundance, lessened injury.ConclusionThese data show health.Lay summaryHepatitis acute worldwide. thought contribute now limit Hepatitis models. pathogenesis. These health.