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The 11 th International Workshop on KSHV & Related Agents, Birmingham, UK
Immunology II Abstract 42
MODULATION BY KSHV OF LIGANDS THAT MEDIATE NK CELL RECOGNITION
Alexis Madrid and Don Ganem
HHMI and Dept of Microbiology, UCSF, San Francisco, CA 94143-0552
Abstract
Natural Killer (NK) cells express an array of activating and inhibitory receptors on their
surfaces. The inhibitory receptors generally recognize MHC class I (MHC-I) molecules on
healthy cells, which are therefore not targeted for destruction. Activating receptors
recognize a variety of cellular ligands, many of which are upregulated in pathologic
conditions. The balance of activating and inhibitory signals within the NK cell determines
whether a target cell will be destroyed and an immune response mounted. KSHV
encodes proteins that downregulate MHC-I on infected cells, thus potentially exposing
these cells to NK cell mediated lysis. Therefore we hypothesized that KSHV would also
have evolved mechanisms to evade killing by NK cells, and one potential way to evade
killing is through downregulation of NK activating ligands. To test this hypothesis, we
infected several human cell lines with KSHV, and measured the cell surface levels of the
various NK activating ligands. The surface display of most NK ligands tested was not
affected during infection. However, we found that one NK activating ligand, NKp44-L, is
consistently downregulated during both latent and lytic KSHV infection. We then
screened a KSHV ORF library in order to search for the viral gene product responsible for
this activity, and identified this protein as Kaposin B. However, Nkp44-L downregulation
is not due to Kaposin B’s known function in activating the p38/MK2 signaling pathway,
and likely reflects an additional activity of the molecule. Studies of the mechanism by
which Kaposin B downregulates NKp44-L are ongoing and will be reported.
Presenting author Email: Alexis.madrid@ucsf.edu
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