The Human Cytomegalovirus UL11 Protein Interacts with the Receptor Tyrosine Phosphatase CD45, Resulting in Functional Paralysis of T Cells

• DOI: 10.1371/journal.ppat.1002432
• Publication Date: 2011-12-08T21:52:40Z
• Authors: Ildar Gabaev; Lars Steinbrück; Claudia Pokoyski; Andreas Pich; Richard J. Stanton; Reinhard Schwinzer; Thomas F. Schulz; Roland Jacobs; Martin Messerle; Penelope C. Kay-F...
• Keywords: Microscopy, Confocal; QH301-705.5; Reverse Transcriptase Polymerase Chain Reaction; T-Lymphocytes; Cytomegalovirus; Cell Separation; RC581-607; Flow Cytometry; Transfection; R1; Mass Spectrometry; QR; Cell Line; 3. Good health; Viral Proteins; 03 medical and health sciences; 0302 clinical medicine; Cytomegalovirus Infections; Humans; Leukocyte Common Antigens; Immunologic diseases. Allergy; Biology (General); Research Article

Human cytomegalovirus (CMV) exerts diverse and complex effects on the immune system, not all of which have been attributed to viral genes. Acute CMV infection results in transient restrictions T cell proliferative ability, can impair control virus increase risk secondary infections patients with weakened or immature systems. In a search for new immunomodulatory proteins, we investigated UL11 protein, member RL11 family. This protein family is defined by domain, has homology immunoglobulin domains adenoviral proteins. We show that pUL11 expressed surface induces intercellular interactions leukocytes. was demonstrated be due interaction receptor tyrosine phosphatase CD45, identified mass spectrometry analysis pUL11-associated CD45 expression sufficient mediate required binding cells, indicating specific ligand. pivotal function regulating signaling thresholds; its absence, Src kinase Lck inactive through (TCR) therefore shut off. presence pUL11, several CD45-mediated functions were inhibited. The induction phosphorylation multiple proteins upon TCR stimulation reduced proliferation impaired. conclude immunosuppressive properties, disruption via inhibition previously unknown strategy CMV.