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  • The EMBO Journal (2002) 21, 1638 - 1649
  • doi:10.1093/emboj/21.7.1638

Multiple endocytic trafficking pathways of MHC class I molecules induced by a Herpesvirus protein

Robert E. Means1,4, Satoshi Ishido2,4, Xavier Alvarez3 and Jae U. Jung1

  1. Department of Microbiology and Molecular Genetics, Division of Tumor Virology, Harvard Medical School, One Pine Hill Drive, Southborough, MA 01772, USA
  2. Department of Microbiology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017, Japan
  3. Department of Pathology, New England Regional Primate Research Center, Harvard Medical School, One Pine Hill Drive, Southborough, MA 01772, USA
  4. R.E.Means and S.Ishido contributed equally to this work

Correspondence to:

Jae U. Jung, E-mail: jae_jung@hms.harvard.edu

Received 23 August 2001; Accepted 5 February 2002; Revised 28 January 2002

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.

  • Keywords:

    • endocytosis,
    • intercellular trafficking,
    • KSHV K3,
    • MHC class I,
    • viral immune evasion