Herpesviral protein targets a cellular WD repeat endosomal protein to downregulate T lymphocyte receptor expression

Junsoo Park, Bok Soo Lee, Joong Kook Choi, Robert E. Means, Joonho Choe, Jae U. Jung

Research output: Contribution to journalArticlepeer-review

49 Citations (Scopus)

Abstract

Herpesvirus saimiri Tip associates with Lck and downregulates Lck signal transduction. Here we demonstrate that Tip targets a lysosomal protein p80, which consists of an N-terminal WD repeat domain and a C-terminal coiled-coil domain. Interaction of Tip with p80 facilitated lysosomal vesicle formation and subsequent recruitment of Lck into the lysosomes for degradation. Consequently, Tip interactions with Lck and p80 result in downregulation of T cell receptor (TCR) and CD4 surface expression. Remarkably, these actions of Tip are functionally and genetically separable: the N-terminal p80 interaction is responsible for TCR downregulation and the C-terminal Lck interaction is responsible for CD4 downregulation. Thus, lymphotropic herpesvirus has evolved an elaborate mechanism to deregulate lymphocyte receptor expression to disarm host immune control.

Original languageEnglish
Pages (from-to)221-233
Number of pages13
JournalImmunity
Volume17
Issue number2
DOIs
Publication statusPublished - 2002 Aug

Bibliographical note

Funding Information:
We especially thank Dr. A. Weiss for providing JCaM1 cells and Dr. S. Gygi at the Harvard Mass Spectrometry facility for sequencing the p80 protein. This work was partly supported by U.S. Public Health Service grants CA31363, CA82057, AI38131, and RR00168 and ACS grant RPG001102. J.P. and J.C. are partly supported by Brain Korea 21 program of Ministry of Education in Korea, R.E.M. is a Cancer Research Institute fellow, and J.J. is a Leukemia & Lymphoma Society Scholar.

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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