title: Resistance to rabies virus infection conferred by the PMLIV isoform.
abstract: Various reports implicate PML and PML nuclear bodies (NBs) in an intrinsic antiviral response targeting diverse cytoplasmic replicating RNA viruses. PML conjugation to the small ubiquitin-like modifier (SUMO) is required for its localization within NBs. PML displays antiviral effects in vivo, as PML deficiency renders mice more susceptible to infection with the rhabdovirus vesicular stomatitis virus (VSV). Cells derived from these mice are also more sensitive to infection with rabies virus, another member of the rhabdovirus family. Alternative splicing from a single gene results in the synthesis of several PML isoforms, and these are classified into seven groups, designated PMLI to -VII. We report here that expression of PMLIV or PMLIVa, which is missing exon 5, inhibited viral mRNA and protein synthesis, leading to a reduction in viral replication. However, the expression of other nuclear isoforms (PMLI to -VI) and cytoplasmic PMLVIIb failed to impair viral production. This antiviral effect required PMLIV SUMOylation, as it was not observed with PMLIV 3KR, in which the lysines involved in SUMO conjugation were mutated. Thus, PMLIV and PMLIVa may exert this isoform-specific function through interaction with specific NB protein partners via their common C-terminal region.
authors: UPR 3296 CNRS, 91198 Gif sur Yvette, France.
authors: Danielle
authors: D
authors: Blondel
authors: Sabrina
authors: S
authors: Kheddache
authors: Xavier
authors: X
authors: Lahaye
authors: Laurent
authors: L
authors: Dianoux
authors: Mounira K
authors: MK
authors: Chelbi-Alix
mesh_terms: D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D017931:DNA Primers / Q000235:genetics; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology; D007370:Interferon Type I / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D000071156:Promyelocytic Leukemia Protein; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012367:RNA, Viral / Q000096:biosynthesis / Q000235:genetics; D011818:Rabies / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control*; D011820:Rabies virus / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity* / Q000502:physiology; D011994:Recombinant Proteins; D058207:Sumoylation; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D025521:Tumor Suppressor Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D014779:Virus Replication
chemical_list: D017931:DNA Primers; D007370:Interferon Type I; D009687:Nuclear Proteins; C513293:Pml protein, mouse; D000071156:Promyelocytic Leukemia Protein; D020033:Protein Isoforms; D012333:RNA, Messenger; D012367:RNA, Viral; D011994:Recombinant Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins