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Journal of Virology, January 2007, p. 474-482, Vol. 81, No. 2
0022-538X/07/$08.00+0     doi:10.1128/JVI.01777-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

The Switch from Latent to Productive Infection in Epstein-Barr Virus-Infected B Cells Is Associated with Sensitization to NK Cell Killing{triangledown}

Isabel Y. Pappworth,1 Eddie C. Wang,1 and Martin Rowe1,2*

Department of Medical Biochemistry and Immunology, Wales College of Medicine, Cardiff University, Heath Park CF14 4XX, United Kingdom,1 Division of Cancer Studies, University of Birmingham Medical School, Edgbaston, Birmingham B15 2TT, United Kingdom2

Received 16 August 2006/ Accepted 25 October 2006

Following activation of Epstein-Barr virus (EBV)-infected B cells from latent to productive (lytic) infection, there is a concomitant reduction in the level of cell surface major histocompatibility complex (MHC) class I molecules and an impaired antigen-presenting function that may facilitate evasion from EBV-specific CD8+ cytotoxic T cells. In some other herpesviruses studied, most notably human cytomegalovirus (HCMV), evasion of virus-specific CD8+ effector responses via downregulation of surface MHC class I molecules is supplemented with specific mechanisms for evading NK cells. We now report that EBV differs from HCMV in this respect. While latently infected EBV-positive B cells were resistant to lysis by two NK lines and by primary polyclonal NK cells from peripheral blood, these effectors efficiently killed cells activated into the lytic cycle. Susceptibility to NK lysis coincided not only with downregulation of HLA-A, -B, and -C molecules that bind to the KIR family of inhibitory receptors on NK cells but also with downregulation of HLA-E molecules binding the CD94/NKG2A inhibitory receptors. Conversely, ULBP-1 and CD112, ligands for the NK cell-activating receptors NKG2D and DNAM-1, respectively, were elevated. Susceptibility of the virus-producing target cells to NK cell lysis was partially reversed by blocking ULBP-1 or CD112 with specific antibodies. These results highlight a fundamental difference between EBV and HCMV with regards to evasion of innate immunity.

* Corresponding author. Mailing address: Division of Cancer Studies, University of Birmingham Medical School, Edgbaston, Birmingham B15 2TT, United Kingdom. Phone: 44 121 4147144. Fax: 44 121 4144486. E-mail: m.rowe{at}bham.ac.uk.

{triangledown} Published ahead of print on 1 November 2006.

Journal of Virology, January 2007, p. 474-482, Vol. 81, No. 2
0022-538X/07/$08.00+0     doi:10.1128/JVI.01777-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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