Measles virus-induced immunosuppression in vitro is independent of complexglycosylation of viral glycoproteins and of hemifusion

Expression of the measles virus (Rn) F/H complex on the surface of viral pa rticles, infected cells, or cells transfected to express these proteins (pr esenter cells [PC]) is necessary and sufficient to induce proliferative arr est in both human and rodent lymphoid cells (responder cells [RC]), This in hibition 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 o r PC also do not contribute to MV-induced immunosuppression in vitro. Using an inhibitor of Golgi-resident mannosidases (deoxymannojirimycin), we foun d that complex glycosylation of the F and H proteins is not required for th e induction of proliferative arrest of RC, As revealed by our previous stud ies, proteolytic cleavage of the MV F protein precursor into its Fl 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 no t interfere with the induction of proliferative inhibition. We now show tha t Z-fFG inhibits cellular fusion at the stage of hemifusion by preventing l ipid mixing of the outer membrane lager. These results provide strong evide nce for a receptor-mediated signal elicited by the IMV Fin complex which ca n be uncoupled from its fusogenic activity is required for the induction of proliferative arrest of human lymphocytes.