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Journal of Virology, August 2000, p. 7548-7553, Vol. 74, No. 16
Institute for Virology and Immunobiology,
University of Würzburg, D-97078
Würzburg,1 and Institute for
Virology, University of Marburg, D-35037
Marburg,2 Germany
Received 29 November 1999/Accepted 18 May 2000
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.
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Measles Virus-Induced Immunosuppression In Vitro Is
Independent of Complex Glycosylation of Viral Glycoproteins and
of Hemifusion
*
Corresponding author. Mailing address: Institute for
Virology, Versbacher Str. 7, D-97078 Würzburg, Germany. Phone:
49-931-201-3895. Fax: 49-931-201-5954. E-mail:
termeulen{at}vim.uni-wuerzburg.de.
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