Acetaldehyde Suppresses HBV-MHC Class I Complex Presentation on Hepatocytes Via Induction of ER Stress and Golgi Fragmentation.

Acetaldehyde Suppresses HBV-MHC Class I Complex Presentation on Hepatocytes Via Induction of ER Stress and Golgi Fragmentation. Am J Physiol Gastrointest Liver Physiol. 2020 Aug 05;: Authors: Ganesan M, Mathews S, Makarov E, Petrosyan A, Kharbanda KK, Kidambi S, Poluektova LI, Casey CA, Osna NA Abstract Alcohol consumption worsens HBV- infection pathogenesis. We have recently reported that acetaldehyde suppressed HBV-peptide-MHC class I complex display on hepatocytes, limiting recognition and subsequent removal of the infected hepatocytes by HBV-specific cytotoxic T lymphocytes (CTLs). This suppression was attributed to impaired processing of antigenic peptides by the proteasome. However, in addition to proteasome dysfunction, alcohol may induce endoplasmic reticulum (ER) stress and Golgi fragmentation in HBV-infected liver cells to reduce uploading of viral peptides to MHC class I and/or trafficking of this complex to the hepatocyte surface. Hence, the aim of this study was to elucidate whether alcohol-induced ER stress and Golgi fragmentation affect HBV peptide-MHC class I complex presentation on HBV+ hepatocytes. Here, we demonstrate that while both acetaldehyde and HBV independently cause ER stress and Golgi fragmentation, the combined exposure provided an additive effect. Thus, we observed an activation of the IRE1α-XBP1 and ATF6α, but not pPERK-peIF2α-ATF4-CHOP arms of ER-stress in HBV-transfected cells treated with acetalde...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - Category: Physiology Authors: Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research