The conserved dileucine- and tyrosine-based motifs in MLV and MPMV envelope glycoproteins are both important to regulate a common Env intracellular trafficking.
BACKGROUND
Retrovirus particles emerge from the assembly of two structural protein components, Gag that is translated as a soluble protein in the cytoplasm of the host cells, and Env, a type I transmembrane protein. Because both components are translated in different intracellular compartments, elucidating the mechanisms of retrovirus assembly thus requires the study of their intracellular trafficking.


RESULTS
We used a CD25 (Tac) chimera-based approach to study the trafficking of Moloney murine leukemia virus and Mason-Pfizer monkey virus Env proteins. We found that the cytoplasmic tails (CTs) of both Env conserved two major signals that control a complex intracellular trafficking. A dileucine-based motif controls the sorting of the chimeras from the trans-Golgi network (TGN) toward endosomal compartments. Env proteins then follow a retrograde transport to the TGN due to the action of a tyrosine-based motif. Mutation of either motif induces the mis-localization of the chimeric proteins and both motifs are found to mediate interactions of the viral CTs with clathrin adaptors.


CONCLUSIONS
This data reveals the unexpected complexity of the intracellular trafficking of retrovirus Env proteins that cycle between the TGN and endosomes. Given that Gag proteins hijack endosomal host proteins, our work suggests that the endosomal pathway may be used by retroviruses to ensure proper encountering of viral structural Gag and Env proteins in cells, an essential step of virus assembly.
Blot
Vincent
V
Institut Cochin, Département Biologie Cellulaire, Paris, F-75014 France. Vincent.blot@normalesup.org
Lopez-Vergès
Sandra
S
Breton
Marie
M
Pique
Claudine
C
Berlioz-Torrent
Clarisse
C
Grange
Marie-Pierre
MP
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D017124:Conserved Sequence; D015686:Gene Products, env / Q000235:genetics / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D007930:Leucine / Q000737:chemistry*; D009052:Leukemia Virus, Murine / Q000378:metabolism*; D016093:Mason-Pfizer monkey virus / Q000378:metabolism*; D008969:Molecular Sequence Data; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D017386:Sequence Homology, Amino Acid; D014443:Tyrosine / Q000737:chemistry*; D021601:trans-Golgi Network / Q000378:metabolism
D015686:Gene Products, env; D015375:Receptors, Interleukin-2; D014443:Tyrosine; D007930:Leucine