HBV shows different levels of adaptation to HLA class I-associated selection pressure correlating with markers of replication

• DOI: 10.1016/j.jhep.2024.10.047
• Publication Date: 2024-11-12T20:15:39Z
• Authors: Tatjana Schwarz; Johannes Ptok; Maximilian Damagnez; Christopher Menne; Elahe Salimi Alizei; Julia Lang-Meli; Michelle Maas; Daniel Habermann; Daniel Hoffmann; Julian Schulze zu...; Georg M. Lauer; Helenie Kefalakes; Markus Cornberg; Anke R.M. Kraft; Smaranda Gliga; Hans H. Bock; Peter A. Horn; Mala K. Maini; Robert Thimme; Heiner Wedemeyer; Jacob Nattermann; Falko M. Heinemann; Tom Luedde; Christoph Neumann...; Andreas Walker; Jörg Timm
• Keywords: Replication

Immune responses by CD8 T cells are essential for control of HBV replication. Although selection escape mutations in T-cell epitopes has been previously described infection, its overall influence on sequence diversity and correlation with markers replication remain unclear. Whole-genome sequencing was applied to isolates from 532 patients chronic infection high-resolution HLA class I genotyping. Using a Bayesian model (HAMdetector) identification HLA-associated mutational states (HAMs), the frequency location residues under pressure were determined levels adaptation individual quantified. published thresholds HAMs, total 295 showed evidence escape, majority which located unidentified epitopes. Interestingly, HAMs highly enriched core protein compared all other proteins. When compared, different immune noted. The level increased patient age correlated replication, low HBeAg-positive infection. Furthermore, negatively viral load HBsAg levels, consistent high I-associated levels. is shaped being predominant target selection. Importantly, observed between stages, need be considered context T-cell-based therapies. response mediated plays critical role controlling shows promise therapeutic strategies aimed at achieving functional cure. This study demonstrates that within common represents key factor failure control. Notably, emerges as primary pressure. Additionally, indicates immunity may transitions phases