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Journal of Virology, February 1999, p. 1350-1361, Vol. 73, No. 2
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Interactions of the Cytoplasmic Domains of Human
and Simian Retroviral Transmembrane Proteins with Components of the
Clathrin Adaptor Complexes Modulate Intracellular and Cell Surface
Expression of Envelope Glycoproteins
Clarisse
Berlioz-Torrent,1
Barbara L.
Shacklett,2
Lars
Erdtmann,1
Lelia
Delamarre,3
Isabelle
Bouchaert,4
Pierre
Sonigo,2
Marie Christine
Dokhelar,3 and
Richard
Benarous1,*
CJF 97/03 INSERM, Interactions
Moléculaires, Hôte-Pathogène,1
Génétique des virus CNRS UPR
0415,2
INSERM
U332,3 and
Service de
Cytométrie,4 Institut Cochin de
Génétique Moléculaire, 75014 Paris, France
Received 13 July 1998/Accepted 30 October 1998
The cytoplasmic domains of the transmembrane (TM) envelope proteins
(TM-CDs) of most retroviruses have a Tyr-based motif, YXXØ, in their
membrane-proximal regions. This signal is involved in the trafficking
and endocytosis of membrane receptors via clathrin-associated AP-1 and
AP-2 adaptor complexes. We have used CD8-TM-CD chimeras to investigate
the role of the Tyr-based motif of human immunodeficiency virus type 1 (HIV-1), simian immunodeficiency virus (SIV), and human T-leukemia
virus type 1 (HTLV-1) TM-CDs in the cell surface expression of the
envelope glycoprotein. Flow cytometry and confocal microscopy studies
showed that this motif is a major determinant of the cell surface
expression of the CD8-HTLV chimera. The YXXØ motif also plays a key
role in subcellular distribution of the envelope of lentiviruses HIV-1
and SIV. However, these viruses, which encode TM proteins with a long
cytoplasmic domain, have additional determinants distal to the YXXØ
motif that participate in regulating cell surface expression. We have
also used the yeast two-hybrid system and in vitro binding assays to
demonstrate that all three retroviral YXXØ motifs interact with the
µ1 and µ2 subunits of AP complexes and that the C-terminal regions
of HIV-1 and SIV TM proteins interact with the
2 adaptin subunit.
The TM-CDs of HTLV-1, HIV-1, and SIV also interact with the whole AP
complexes. These results clearly demonstrate that the cell surface
expression of retroviral envelope glycoproteins is governed by
interactions with adaptor complexes. The YXXØ-based signal is the
major determinant of this interaction for the HTLV-1 TM, which contains
a short cytoplasmic domain, whereas the lentiviruses HIV-1 and SIV have additional determinants distal to this signal that are also involved.
*
Corresponding author. Mailing address: CJF 97/03
INSERM, Interactions Moléculaires Hôte-Pathogène,
Institut Cochin de Génétique Moléculaire (ICGM), 24 rue du faubourg St Jacques, 75014 Paris, France. Phone: 33 1 44 41 24 65 Fax: 33 1 44 41 23 99. E-mail: benarous{at}icgm.cochin.inserm.fr.
Journal of Virology, February 1999, p. 1350-1361, Vol. 73, No. 2
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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