Journal Article

pUS6 in pseudorabies virus participates in the process of inhibiting antigen presentation by inhibiting the assembly of peptide loading complex

Ma, Ningning, Chen, Lu, Li, Yongtao, Sun, Yawei, Yu, Linyang, Ding, Chenmeng

2024

Overview

Pseudorabies virus (PRV) can establish lifelong latent infection in peripheral nervous ganglion, and persistent infections in peripheral blood lymphocytes. Establishing an infection in the lymphocytes does not only enable the PRV to escape host immune surveillance but pass through the placental barrier, leading to fetal death and abortion. Due to the pathogenicity of the PRV, it poses a huge challenge in its prevention and control. The PRV escapes host immunity through downregulation of swine leukocyte antigen class I (SLA I) molecules on infected cells. However, data on the molecular mechanisms of the SLA I suppression remains scant. Here, in order to verify the effect of candidate proteins PRV pUL44 and pUS6 on PRV immune escape related molecules SLA I and peptide loading complex (PLC), we detected the expression of SLA I and PLC components after expressing PRV pUL44 and pUS6. The effects of pUS6 and pUL44 on SLA I and PLC were analyzed by qRT-PCR and Western blot at mRNA and protein level, respectively. Cells expressing pUS6 or pUL44 genes showed a significantly suppressed expression of surface and total SLA I molecules. In addition, unlike UL44, the US6 gene was shown to downregulate the transporter associated with antigen processing 1 (TAP1), TAP2 and Tapasin molecules. The results show that PRV pUS6 may participate in virus immune escape by directly regulating the SLA I, TAP dimer and Tapasin molecules, thus blocking the transportation of TAP-bound peptides to the ER to bind SLA I molecules. We provide a theoretical basis on the mechanism of TAP mediated immune escape by the PRV.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Animals / Antibodies / Antigen Presentation / Antigen processing / Antigens / Aujeszky's disease / Care and treatment / carrier state / Cell Line / class / Down-regulation / Endoplasmic reticulum / fetal death / Fetuses / ganglia / genes / Health aspects / Herpes viruses / Herpesvirus 1, Suid - immunology / Histocompatibility Antigens Class I - immunology / Histocompatibility Antigens Class I - metabolism / Hogs / Immune escape / Immune evasion / Immunosurveillance / Latent infection / leukocytes / Lymphocytes / Medicine / Medicine & Public Health / Molecular modelling / monitoring / mRNA / Pathogenicity / Peptides / Peripheral blood / Physiological aspects / Plasmids / PLC / Prevention / protein content / Proteins / Pseudorabies / Pseudorabies - immunology / Pseudorabies - virology / Pseudorabies virus / SLA I / Suid alphaherpesvirus 1 / Swine / TAP / TAP protein / Tapasin / Transgenics / Veterinary Medicine/Veterinary Science / Viral Proteins - genetics / Viral Proteins - metabolism / Viruses / Western blotting / Zoology