Hepatitis C virus modulates signal peptide peptidase to alter host protein processing

Abstract

Immunoevasins are viral proteins that prevent antigen presentation on major histocompatibility complex (MHC) class I, thus evading host immune recognition. Hepatitis C virus (HCV) evades immune surveillance to induce chronic infection; however, how HCV-infected hepatocytes affect immune cells and evade immune recognition remains unclear. Herein, we demonstrate that HCV core protein functions as an immunoevasin. Its expression interfered with the maturation of MHC class I molecules catalyzed by the signal peptide peptidase (SPP) and induced their degradation via HMG-CoA reductase degradation 1 homolog, thereby impairing antigen presentation to CD8+ T cells. The expression of MHC class I in the livers of HCV core transgenic mice and chronic hepatitis C patients was impaired but was restored in patients achieving sustained virological response. Finally, we show that the human cytomegalovirus US2 protein, possessing a transmembrane region structurally similar to the HCV core protein, targets SPP to impair MHC class I molecule expression. Thus, SPP represents a potential target for the impairment of MHC class I molecules by DNA and RNA viruses.

Hydrazineylidene‐3‐oxopropanal derivatives as antiviral agents for treatment of HBV and HCV: Experimental, DFT, and molecular docking studies

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Exploring Effect of Medication Adherence on Quality of Life among Newly Treated Hepatitis “C” Virus Patients

“…It develops over years to be chronic in 70% of patients with the presence of various symptoms related to liver damage. Acute hepatitis C symptoms are more shortterm, lasting six months or less; whereas, chronic hepatitis can last for the entire life requiring long-term treatment (Hirano et al, 2021;Hudson et al, 2022).…”

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