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Multiple endocytic trafficking pathways of MHC class I molecules induced by a Herpesvirus protein
Author(s) -
Means Robert E.,
Ishido Satoshi,
Alvarez Xavier,
Jung Jae U.
Publication year - 2002
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/21.7.1638
Subject(s) - biology , mhc class i , major histocompatibility complex , microbiology and biotechnology , internalization , mhc restriction , endocytosis , endocytic cycle , endosome , transporter associated with antigen processing , mhc class ii , cd74 , effector , immune system , genetics , cell , intracellular
The K3 protein of a human tumor‐inducing herpesvirus, Kaposi's sarcoma‐associated herpesvirus (KSHV), down‐regulates major histocompatibility complex (MHC) class I surface expression by increasing the rate of endocytosis. In this report, we demonstrate that the internalization of MHC class I by the K3 protein is the result of multiple, consecutive trafficking pathways that accelerate the endocytosis of class I molecules, redirect them to the trans ‐Golgi network (TGN), and target MHC class I to the lysosomal compartment. Remarkably, these actions of K3 are functionally and genetically separable; the N‐terminal zinc finger motif and the central sorting motif are involved in triggering internalization of MHC class I molecules and redirecting them to the TGN. Subsequently, the C‐terminal diacidic cluster region of K3 is engaged in targeting MHC class I molecules to the lysosomal compartment. These results demonstrate a novel trafficking mechanism of MHC class I molecules induced by KSHV K3, which ensures viral escape from host immune effector recognition.