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

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Abstract

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.

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Acknowledgements

We are grateful to Begoña Galocha for experimental help and discussions. We also thank Biomol-Informatics SL (www.biomol-informatics.com) for bioinformatics consulting. This work was supported by grants from the Spanish Ministerio de Ciencia y Tecnología (BFU2007-63110/BMC), from the European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement KBBE- 211691- ASFRISK and from Laboratorios del Dr. Esteve, SA, and also by institutional grants from the Fundación Ramón Areces and Banco Santander Central Hispano. C.H. and A.G.G. also acknowledge financial support from the Centro de Investigación en Sanidad Animal (CISA).

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Authors and Affiliations

  1. Centro de Biología Molecular “Severo Ochoa”, (C.S.I.C.-U.A.M.) Consejo Superior de Investigaciones Cientificas, Universidad Autónoma de Madrid, 28049, Madrid, Spain

    Carolina Hurtado, Maria José Bustos, Patricia de León, Prado Sabina, Paulino Gómez-Puertas, Yolanda Revilla & Angel L. Carrascosa

  2. Lymphocyte Interaction Lab, Cancer Research UK London Research Institute, Lincoln’s Inn Fields Laboratories, 44 Lincoln’s Inn Fields, London, WC2A 3PX, United Kingdom

    Aitor G. Granja

  3. Biomol-Informatics SL, Parque Científico de Madrid, Campus de Cantoblanco, 28049, Madrid, Spain

    Eduardo López-Viñas

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  1. Carolina Hurtado
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  2. Maria José Bustos
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Correspondence to Angel L. Carrascosa.

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Hurtado, C., Bustos, M.J., Granja, A.G. et al. The African swine fever virus lectin EP153R modulates the surface membrane expression of MHC class I antigens. Arch Virol 156, 219–234 (2011). https://doi.org/10.1007/s00705-010-0846-2

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  • DOI: https://doi.org/10.1007/s00705-010-0846-2

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