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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Figure 1

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KSHV lytic replication decreases CD1d levels. (A) The levels of CD1d on ...
KSHV lytic replication decreases CD1d levels. (A) The levels of CD1d on uninduced BCBL-1 cells, which are latently infected with KSHV. The background level of antibody staining of BCBL-1 cells is shown (2° alone). (B) BCBL-1 cells were induced to enter the lytic replication cycle and allowed to proceed to 4 days after induction, after which the cells in the late portion of the lytic cycle could be monitored by K8.1 expression. The cells were stained with a rabbit primary antibody against K8.1 and an anti-rabbit secondary antibody, and with a Zenon-1–APC–labeled antibody against CD1d and a PE-conjugated antibody against transferrin receptor (TfnR). The levels of CD1d for both the K8.1-positive [K8.1(+)] and K8.1-negative [K8.1(–)] populations were determined. To ensure that induction of lytic replication does not cause a general downregulation, the normal level of transferrin receptor was determined by analyzing a bulk population of K8.1-positive cells and creating a gate into which 80% of the cells fell. The K8.1-positive and K8.1-negative populations both showed similar levels of transferrin receptor; thus even in a nongated population, most cells had normal levels of cell-surface receptors.