Abstract
Since the publication of the DRiP (defective ribosomal product) hypothesis in 1996, numerous studies have addressed the contribution of DRiPs to generating viral antigenic peptides for CD8+ T cell immunosurveillance. Here, we review studies characterizing the generation of antigenic peptides from influenza A virus encoded DRiPs, discuss the many remaining mysteries regarding the nature of their co-translational generation, and speculate on where the future might lead.
Highlights
Influenza A virus (IAV), a negative-sense, single-stranded, segmented RNA virus, causes significant worldwide morbidity, mortality and economic burden due to its evasion of adaptive immunity, despite repeated infection and vaccination
Since the publication of the DRiP hypothesis in 1996, numerous studies have addressed the contribution of DRiPs to generating viral antigenic peptides for CD8? T cell immunosurveillance
We review studies characterizing the generation of antigenic peptides from influenza A virus encoded DRiPs, discuss the many remaining mysteries regarding the nature of their co-translational generation, and speculate on where the future might lead
Summary
Influenza A virus (IAV), a negative-sense, single-stranded, segmented RNA virus, causes significant worldwide morbidity, mortality and economic burden due to its evasion of adaptive immunity, despite repeated infection and vaccination. T cell immunosurveillance of MHC class I-peptide complexes, a crucial part of the adaptive immune system, recognizes peptides encoded by each of the eight IAV gene segments, limits viral replication and reduces morbidity and mortality in hosts whose antibody responses fail to prevent infection (McMichael et al 1983; Kim et al 2011). By binding and presenting oligopeptides at the cell surface, MHC class I molecules provide a window into the translational status of cells. MHC class I antigenic peptides encoded by host or viral genes have two potential sources: ‘‘retirees’’ (Yewdell 2001, 2003) and DRiPs (defective ribosomal products) (Yewdell et al 1996). Numerous studies support that immunological relevant viral peptides predominately originate from DRiPs, including products from downstream initiation on AUG codons (Berglund et al 2007), frame shifting (Fetten et al 1991; Bullock and Eisenlohr 1996; Elliott et al 1996; Zook et al 2006), initiation on non-AUG start codons (Yang et al 2016), stop codon read through, and translation of viral RNA in the nucleus (Dolan et al 2010a)
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