African swine fever virus lectin EP153R modulates the surface membrane expression of MHC class I antigens

• Published in: Archives of virology 2011-02, Vol.156 (2), p.219-234
• Main Authors: Hurtado, Carolina, Bustos, Maria José, Granja, Aitor G, de León, Patricia, Sabina, Prado, López-Viñas, Eduardo, Gómez-Puertas, Paulino, Revilla, Yolanda, Carrascosa, Angel L
• Format: Article
• Language: English
• Subjects: African swine fever; African swine fever virus; African Swine Fever Virus - genetics; African Swine Fever Virus - immunology; Amino Acid Sequence; Animals; Antigens; Asfarviridae; Base Sequence; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; CD69 antigen; Cell Line; Dimerization; DNA, Viral - genetics; Down-Regulation; Endoplasmic Reticulum - virology; Exocytosis; Fundamental and applied biological sciences. Psychology; Gene expression; Genes, Viral; Glycosylation; Histocompatibility Antigens Class I - chemistry; Histocompatibility Antigens Class I - metabolism; Histocompatibility Antigens Class II - chemistry; Histocompatibility Antigens Class II - metabolism; Humans; Infectious Diseases; Lectins, C-Type - chemistry; Lectins, C-Type - genetics; Lectins, C-Type - immunology; Medical Microbiology; Mice; Microbiology; Miscellaneous; Models, Molecular; Molecular Sequence Data; Original Article; Protein Interaction Domains and Motifs; Protein Structure, Quaternary; Recombinant Proteins - chemistry; Recombinant Proteins - genetics; Recombinant Proteins - immunology; Recombinants; Sequence Homology, Amino Acid; Static Electricity; Structural Homology, Protein; Swine; Transfection; Viral Proteins - chemistry; Viral Proteins - genetics; Viral Proteins - immunology; Virology; Viruses
• ISSN: 0304-8608; 1432-8798
• DOI: 10.1007/s00705-010-0846-2

We have modeled a 3D structure for the C-type lectin domain of the African swine fever virus protein EP153R, based on the structure of CD69, CD94 and Ly49A cell receptors, and this model predicts that a dimer of EP153R may establish an asymmetric interaction with one MHC-I molecule. A functional consequence of this interaction could be the modulation of MHC-I expression. By using both transfection and virus infection experiments, we demonstrate here that EP153R inhibits MHC-I membrane expression, most probably by impairing the exocytosis process, without affecting the synthesis or glycosylation of MHC antigens. Interestingly, the EP153-mediated control of MHC requires the intact configuration of the lectin domain of the viral protein, and specifically the R133 residue. Interference of EP153R gene expression during virus infection and studies using virus recombinants with the EP153R gene deleted further support the inhibitory role of the viral lectin on the expression of MHC-I antigens.