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J. Biol. Chem., Vol. 276, Issue 47, 44239-44246, November 23, 2001
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From the Molecular Medicine Program, Mayo Foundation,
Rochester, Minnesota 55905
The endoplasmic reticulum (ER) was
investigated as the initial oligomerization site for the envelope
glycoproteins H and F of measles virus (MV), a clinically relevant
member of the Paramyxoviridae family, and consequences of this
interaction for viral replication were studied. Both proteins were
tagged at their cytosolic tails with RRR and KKXX motifs,
respectively, resulting in their efficient retention in the ER.
Co-transfection of the retained constructs with transport competent MV
glycoproteins revealed a dominant negative effect on their biological
activity indicating intracellular complex formation and thus retention.
Pulse-chase analysis and co-immunoprecipitation
experiments demonstrated that this effect is based on
both homo- and hetero-oligomerization in the ER.
Recombinant viruses additionally expressing
ER-retained F showed an altered cytopathic phenotype accompanied
by greatly reduced particle release. Similar mutant viruses
additionally expressing ER-retained H could not be rescued indicating
an even greater negative effect of this protein on virus viability. Our
study suggests that both homo- and hetero-oligomerization of MV
glycoproteins occur in the ER and that these events are of significance
for early steps of particle assembly.
Measles Virus Envelope Glycoproteins
Hetero-oligomerize in the Endoplasmic Reticulum*
,
*
This work was supported by grants from the Siebens and Mayo
Foundations (to R. C.), the Fraternity of the Eagles (to R. K. P.),
and an Emmy-Noether postdoctoral fellowship from the Deutsche Forschungsgemeinschaft (to R. K. P.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Molecular Medicine
Program, Mayo Foundation, 200 1st St. SW, Rochester, MN 55905. Tel.:
507-538-1105; Fax: 507-284-8388; E-mail:
plemper.richard@mayo.edu.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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