Regulation of CD1d expression and function by a herpesvirus infection
David Jesse Sanchez, Jenny E. Gumperz, Don Ganem
David Jesse Sanchez, Jenny E. Gumperz, Don Ganem
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Article Virology

Regulation of CD1d expression and function by a herpesvirus infection

Abstract

Little is known about the role of CD1d-restricted T cells in antiviral immune responses. Here we show that the lytic replication cycle of the Kaposi sarcoma–associated herpesvirus (KSHV) promotes downregulation of cell-surface CD1d. This is caused by expression of the 2 modulator of immune recognition (MIR) proteins of the virus, each of which promotes the loss of surface CD1d expression following transfection into uninfected cells. Inhibition of CD1d surface expression is due to ubiquitination of the CD1d α-chain on a unique lysine residue in its cytoplasmic tail, which triggers endocytosis. Unlike MIR-mediated MHC class I downregulation, however, CD1d downregulation does not appear to include accelerated lysosomal degradation. MIR2-induced downregulation of CD1d results in reduced activation of CD1d-restricted T cells in vitro. KSHV modulation of CD1d expression represents a strategy for viral evasion of innate host immune responses and implicates CD1d-restricted T cells as regulators of this viral infection.

Authors

David Jesse Sanchez, Jenny E. Gumperz, Don Ganem

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MIR1 and MIR2 induce CD1d downregulation. (A) BJAB cells were transientl...
MIR1 and MIR2 induce CD1d downregulation. (A) BJAB cells were transiently transfected by electroporation with expression vectors for EGFP, MIR1-EGFP, or MIR2-EGFP. Thirty-six hours after transfection, the cells were stained with Zenon-1–APC–labeled mouse mAbs against human CD1d. Levels of HLA-A, HLA-B, and HLA-C (MHC class I); HLA-DR (MHC class II); CD1d; and Fas are shown. For reference, the nonstained control population is also shown. (B) HepG2 cells, which express a high level of endogenous CD1d, were stably transduced with retroviral vectors encoding either lacZ or Flag-tagged MIR2. A mixed population of stable cells was selected, stained with Zenon-1–APC–labeled mAbs, and analyzed by flow cytometry. As a reference, the histogram for the nonstained control is also shown.