Herpes simplex virus type 1 targets the MHC class II processing pathway for immune evasion

Area of Science:

• Immunology
• Virology
• Molecular Biology

Background:

• Herpes Simplex Virus type 1 (HSV-1) employs strategies to evade host immune responses.
• MHC class II (MHC-II) pathway is crucial for presenting antigens to CD4(+) T cells, essential for adaptive immunity.
• HSV-1 infection impairs B cell antigen presentation, potentially facilitating viral persistence.

Purpose of the Study:

• To investigate how HSV-1 infection impacts the molecular machinery of the MHC-II processing pathway.
• To elucidate the role of viral glycoprotein B (gB) in modulating MHC-II function during infection.

Main Methods:

• Analysis of MHC-II processing components (HLA-DR, HLA-DM, invariant chain) in HSV-1 infected cells.
• Investigation of viral glycoprotein B (gB) interactions with MHC-II pathway molecules.
• Assessment of subcellular localization and cell surface expression of MHC-II complexes.

Main Results:

• HSV-1 infection significantly reduces invariant chain (Ii) expression, impairing HLA-DR-peptide complex formation.
• Viral glycoprotein B (gB) directly interacts with HLA-DR, competing with Ii binding and inhibiting MHC-II pathway activity.
• gB also associates with HLA-DM, leading to the export of gB-associated DR and DM heterodimers from the ER.
• DR-gB complexes accumulate in intracellular vesicles, preventing their transport to the cell surface.

Conclusions:

• HSV-1 actively targets and disrupts the MHC-II antigen processing and presentation pathway.
• Viral glycoprotein B is a key mediator of this immune evasion strategy by interfering with HLA-DR and HLA-DM.
• Disruption of MHC-II surface expression limits CD4(+) T cell activation, promoting HSV-1 immune escape.