Lectin EP153R của virus sốt lợn châu Phi điều chỉnh biểu hiện kháng nguyên MHC lớp I trên màng bề mặt

Archives of Virology - Tập 156 - Trang 219-234 - 2010
Carolina Hurtado1, Maria José Bustos1, Aitor G. Granja2, Patricia de León1, Prado Sabina1, Eduardo López-Viñas3, Paulino Gómez-Puertas1, Yolanda Revilla1, Angel L. Carrascosa1
1Centro de Biología Molecular “Severo Ochoa”, (C.S.I.C.-U.A.M.) Consejo Superior de Investigaciones Cientificas, Universidad Autónoma de Madrid, Madrid, Spain
2Lymphocyte Interaction Lab, Cancer Research UK London Research Institute, Lincoln’s Inn Fields Laboratories, London, United Kingdom
3Biomol-Informatics SL, Parque Científico de Madrid, Campus de Cantoblanco, Madrid, Spain

Tóm tắt

Chúng tôi đã mô hình hóa cấu trúc 3D cho miền lectin loại C của protein EP153R của virus sốt lợn châu Phi, dựa trên cấu trúc của các thụ thể tế bào CD69, CD94 và Ly49A, và mô hình này dự đoán rằng một dimer của EP153R có thể thiết lập tương tác bất đối xứng với một phân tử MHC-I. Một hậu quả chức năng của tương tác này có thể là sự điều tiết biểu hiện MHC-I. Bằng cách sử dụng cả thí nghiệm chuyển gen và lây nhiễm virus, chúng tôi chứng minh rằng EP153R ức chế biểu hiện màng MHC-I, có lẽ bằng cách gây cản trở quá trình xuất bào, mà không ảnh hưởng đến việc tổng hợp hoặc glycosyl hóa các kháng nguyên MHC. Thú vị thay, việc kiểm soát MHC do EP153 thực hiện yêu cầu cấu hình nguyên vẹn của miền lectin của protein virus, và cụ thể là dư lượng R133. Sự can thiệp của biểu hiện gen EP153R trong quá trình lây nhiễm virus và các nghiên cứu sử dụng virus tái tổ hợp với gen EP153R bị xóa càng hỗ trợ vai trò ức chế của lectin virus đối với biểu hiện của các kháng nguyên MHC-I.

Từ khóa

#virus sốt lợn châu Phi #lectin EP153R #MHC lớp I #biểu hiện màng #tương tác bất đối xứng

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