| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Departments of
*
Clinical Immunology and
Haematology, Royal Free Hospital School of Medicine, London, United Kingdom
CMV and other viruses down-regulate the cell surface expression of class I HLA, and while this allows them to evade CTL, it may make infected cells more susceptible to lysis by NK cells, due to the failure to engage class I inhibitory receptors on the NK cell. We studied CMV infection and found that fibroblasts infected with virus strains Towne, Toledo, Davis, and C1FE were refractory to NK lysis, while those infected with strains AD169, C1F, or R7 were susceptible. All viral strains down-regulated class I HLA to a similar extent, and we concluded that there was no evidence for any correlation between the latter and susceptibility to NK lysis. In contrast, there was a strong correlation between NK killing of CMV-infected cells and cell surface levels of lymphocyte function-associated antigen-3 (LFA-3). Fibroblasts infected with the Towne, Toledo, Davis, and C1FE strains of CMV down-regulated LFA-3 expression and were refractory to lysis, while strains AD169, C1F, and R7 up-regulated LFA-3 and were susceptible to NK killing. U373 MG (malignant glioma) cells expressed constitutively high levels of LFA-3 and were sensitive to NK lysis when infected with any of the above-listed CMV strains. We estimated that a minimum of between 29,000 and 71,000 LFA-3 molecules per target cell were needed for NK susceptibility. The effects on LFA-3 expression were due to immediate early/early viral gene products. We also demonstrated that fibroblasts infected with the strains Towne, Toledo, Davis, and C1FE expressed a ganciclovir-sensitive late CMV gene product, which delivered an inhibitory signal to NK cells.
This article has been cited by other articles:
|
|
 |
|
  M. R. Wills, O. Ashiru, M. B. Reeves, G. Okecha, J. Trowsdale, P. Tomasec, G. W. G. Wilkinson, J. Sinclair, and J. G. P. Sissons Human Cytomegalovirus Encodes an MHC Class I-Like Molecule (UL142) That Functions to Inhibit NK Cell Lysis J. Immunol., December 1, 2005; 175(11): 7457 - 7465. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A.-C. Iversen, P. S. Norris, C. F. Ware, and C. A. Benedict Human NK Cells Inhibit Cytomegalovirus Replication through a Noncytolytic Mechanism Involving Lymphotoxin-Dependent Induction of IFN-{beta} J. Immunol., December 1, 2005; 175(11): 7568 - 7574. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Saverino, F. Ghiotto, A. Merlo, S. Bruno, L. Battini, M. Occhino, M. Maffei, C. Tenca, S. Pileri, L. Baldi, et al. Specific Recognition of the Viral Protein UL18 by CD85j/LIR-1/ILT2 on CD8+ T Cells Mediates the Non-MHC-Restricted Lysis of Human Cytomegalovirus-Infected Cells J. Immunol., May 1, 2004; 172(9): 5629 - 5637. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Rolle, M. Mousavi-Jazi, M. Eriksson, J. Odeberg, C. Soderberg-Naucler, D. Cosman, K. Karre, and C. Cerboni Effects of Human Cytomegalovirus Infection on Ligands for the Activating NKG2D Receptor of NK Cells: Up-Regulation of UL16-Binding Protein (ULBP)1 and ULBP2 Is Counteracted by the Viral UL16 Protein J. Immunol., July 15, 2003; 171(2): 902 - 908. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Odeberg, H. Browne, S. Metkar, C. J. Froelich, L. Branden, D. Cosman, and C. Soderberg-Naucler The Human Cytomegalovirus Protein UL16 Mediates Increased Resistance to Natural Killer Cell Cytotoxicity through Resistance to Cytolytic Proteins J. Virol., April 15, 2003; 77(8): 4539 - 4545. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. C. Y. Wang, B. McSharry, C. Retiere, P. Tomasec, S. Williams, L. K. Borysiewicz, V. M. Braud, and G. W. G. Wilkinson From the Cover: UL40-mediated NK evasion during productive infection with human cytomegalovirus PNAS, May 28, 2002; 99(11): 7570 - 7575. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Odeberg and C. Söderberg-Nauclér Reduced Expression of HLA Class II Molecules and Interleukin-10- and Transforming Growth Factor {beta}1-Independent Suppression of T-Cell Proliferation in Human Cytomegalovirus-Infected Macrophage Cultures J. Virol., June 1, 2001; 75(11): 5174 - 5181. [Abstract] [Full Text]
|
|
|
|
|
|
C. Cerboni, M. Mousavi-Jazi, A. Linde, K. Soderstrom, M. Brytting, B. Wahren, K. Karre, and E. Carbone Human Cytomegalovirus Strain-Dependent Changes in NK Cell Recognition of Infected Fibroblasts J. Immunol., May 1, 2000; 164(9): 4775 - 4782. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Tomasec, V. M. Braud, C. Rickards, M. B. Powell, B. P. McSharry, S. Gadola, V. Cerundolo, L. K. Borysiewicz, A. J. McMichael, and G. W. Wilkinson Surface Expression of HLA-E, an Inhibitor of Natural Killer Cells, Enhanced by Human Cytomegalovirus gpUL40 Science, February 11, 2000; 287(5455): 1031 - 1033. [Abstract] [Full Text]
|
|
|
|
 |
|
 G. W. Hunninghake, M. M. Monick, and L. J. Geist Cytomegalovirus Infection . Regulation of Inflammation Am. J. Respir. Cell Mol. Biol., August 1, 1999; 21(2): 150 - 152. [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
