Intra- and intercellular trafficking of the foamy virus auxiliary bet protein.
The Bet protein of foamy viruses (FVs) is an auxiliary protein encoded by the 3' end of the viral genome. Although its function during the viral replication cycle is still unknown, Bet seems to play a key role in the establishment and/or maintenance of viral persistence, representing the predominant viral protein detected during chronic infection. To clarify the function of this viral protein, the subcellular distribution of Bet from the prototypic human foamy virus (HFV) was examined. We report here that this protein is distributed in both the cytoplasm and the nucleus of HFV-infected or Bet-transfected cells. The nuclear targeting results from the presence of a bipartite nuclear localization signal at the C-terminal region, sufficient to direct heterologous reporter proteins to the nucleus. Since HFV Bet spreads between cells, we show here that the secreted protein targets the nuclei of recipient cells. HFV Bet follows an unconventional route to exit the cell since its secretion is not affected by brefeldin A, a drug which disrupts the trafficking between the endoplasmic reticulum and the Golgi complex. Finally, these inter- and intracellular movements were also observed for the equine foamy virus Bet protein, strongly suggesting that these remarkable features are conserved among FVs.
Lecellier
Charles-Henri
CH
CNRS UPR9051, Hôpital Saint-Louis, 75475 Paris Cedex 10, France.
Vermeulen
Wim
W
Bachelerie
Françoise
F
Giron
Marie-Lou
ML
Saïb
Ali
A
D000595:Amino Acid Sequence; D000818:Animals; D020126:Brefeldin A / Q000494:pharmacology; D019556:COS Cells; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002522:Chlorocebus aethiops; D003593:Cytoplasm / Q000378:metabolism; D016679:Genome, Viral; D008969:Molecular Sequence Data; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects; D012191:Retroviridae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016092:Spumavirus / Q000235:genetics / Q000378:metabolism*; D014170:Transformation, Genetic
D011500:Protein Synthesis Inhibitors; D012191:Retroviridae Proteins; C080099:bet protein, human foamy virus; D020126:Brefeldin A