Measles virus-induced immunosuppression in vitro is independent of complex glycosylation of viral glycoproteins and of hemifusion.
Expression of the measles virus (MV) F/H complex on the surface of viral particles, infected cells, or cells transfected to express these proteins (presenter cells [PC]) is necessary and sufficient to induce proliferative arrest in both human and rodent lymphoid cells (responder cells [RC]). This inhibition was found to occur independent of apoptosis and soluble mediators excluded by a pore size filter of 200 nm released from either PC or RC. We now show that reactive oxygen intermediates which might be released by RC or PC also do not contribute to MV-induced immunosuppression in vitro. Using an inhibitor of Golgi-resident mannosidases (deoxymannojirimycin), we found that complex glycosylation of the F and H proteins is not required for the induction of proliferative arrest of RC. As revealed by our previous studies, proteolytic cleavage of the MV F protein precursor into its F1 and F2 subunits, but not of F/H-mediated cellular fusion, was found to be required, since fusion-inhibitory peptides such as Z-D-Phe-L-Phe-Gly (Z-fFG) did not interfere with the induction of proliferative inhibition. We now show that Z-fFG inhibits cellular fusion at the stage of hemifusion by preventing lipid mixing of the outer membrane layer. These results provide strong evidence for a receptor-mediated signal elicited by the MV F/H complex which can be uncoupled from its fusogenic activity is required for the induction of proliferative arrest of human lymphocytes.
Weidmann
A
A
Institute for Virology and Immunobiology, University of Würzburg, D-97078 Würzburg, Germany.
Fischer
C
C
Ohgimoto
S
S
Rüth
C
C
ter Meulen
V
V
Schneider-Schaulies
S
S
D000818:Animals; D002144:Callithrix; D002522:Chlorocebus aethiops; D006031:Glycosylation; D006389:Hemagglutinins, Viral / Q000378:metabolism*; D006801:Humans; D007108:Immune Tolerance; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008459:Measles virus / Q000276:immunology*; D008561:Membrane Fusion / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014709:Vero Cells; D014760:Viral Fusion Proteins / Q000378:metabolism*
D006389:Hemagglutinins, Viral; D017382:Reactive Oxygen Species; D014760:Viral Fusion Proteins; C032397:hemagglutinin protein G, measles virus