Rabies virus P and small P products interact directly with PML and reorganize PML nuclear bodies.
The interferon-induced promyelocytic leukaemia (PML) protein localizes both in the nucleoplasm and in matrix-associated multi-protein complexes known as nuclear bodies (NBs). NBs are disorganized in acute promyelocytic leukaemia or during some viral infections, suggesting that PML NBs could be a part of cellular defense mechanism. Rabies virus, a member of the rhabdoviridae family, replicates in the cytoplasm. Rabies phosphoprotein P and four other amino-terminally truncated products (P2, P3, P4, P5) are all translated from P mRNA. P and P2 are located in the cytoplasm, whereas P3, P4 and P5 are found mostly in the nucleus. Infection with rabies virus reorganized PML NBs. PML NBs became larger and appeared as dense aggregates when analysed by confocal or electron microscopy, respectively. The expression of P sequesters PML in the cytoplasm where both proteins colocalize, whereas that of P3 results in an increase in PML body size, as observed in infected cells. The P and P3 interacted directly in vivo and in vitro with PML. The C-terminal domain of P and the PML RING finger seem to be involved in this binding. Moreover, PML-/- primary mouse embryonic fibroblasts expressed viral proteins at a higher level and produced 20 times more virus than wild-type cells, suggesting that the absence of all PML isoforms resulted in an increase in rabies virus replication.
Blondel
Danielle
D
UMRCNRS2472, 91198 Gif sur Yvette, France.
Regad
Tarick
T
Poisson
Nicolas
N
Pavie
Benjamen
B
Harper
Francis
F
Pandolfi
Pier Paolo
PP
De Thé
Hugues
H
Chelbi-Alix
Mounira K
MK
D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D006224:Cricetinae; D003593:Cytoplasm / Q000378:metabolism; D017931:DNA Primers; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000378:metabolism*; D009687:Nuclear Proteins; D010750:Phosphoproteins / Q000378:metabolism*; D000071156:Promyelocytic Leukemia Protein; D011485:Protein Binding; D014157:Transcription Factors / Q000378:metabolism*; D025521:Tumor Suppressor Proteins; D015678:Viral Structural Proteins / Q000378:metabolism*
D017931:DNA Primers; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C103961:P phosphoprotein, Rabies virus; D010750:Phosphoproteins; C513293:Pml protein, mouse; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D015678:Viral Structural Proteins