Multiple endocytic trafficking pathways of MHC class I molecules induced by a Herpesvirus protein.
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.
Means
Robert E
RE
Department of Microbiology and Molecular Genetics, Division of Tumor Virology, New England Regional Primate Research Center, Harvard Medical School, One Pine Hill Drive, Southborough, MA 01772, USA.
Ishido
Satoshi
S
Alvarez
Xavier
X
Jung
Jae U
JU
D000595:Amino Acid Sequence; D001665:Binding Sites; D001692:Biological Transport; D002461:Cell Line, Transformed; D017124:Conserved Sequence; D015536:Down-Regulation; D004705:Endocytosis; D019288:Herpesvirus 8, Human; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D008969:Molecular Sequence Data; D016296:Mutagenesis; D022161:Transport Vesicles / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D016335:Zinc Fingers; D021601:trans-Golgi Network / Q000378:metabolism
D015395:Histocompatibility Antigens Class I; D017874:Immediate-Early Proteins; C456022:K3 protein, Kaposi's sarcoma-associated herpesvirus; C405867:K5 protein, Human herpesvirus 8; D014764:Viral Proteins