Related Experiment Video
Updated: Jun 10, 2026
In Vitro ELISA Test to Evaluate Rabies Vaccine Potency
Published on: May 11, 2020
Resistance to rabies virus infection conferred by the PMLIV isoform
Danielle Blondel1, Sabrina Kheddache, Xavier Lahaye
1UPR 3296 CNRS, 91198 Gif sur Yvette, France.
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.
Insights
The promyelocytic leukemia (PML) protein isoform IV (PMLIV) and its variant PMLIVa exhibit specific antiviral activity against RNA viruses. This effect depends on PMLIV SUMOylation and may involve interactions with nuclear body proteins.
Area of Science:
- Molecular Biology
- Virology
- Cell Biology
Background:
- The promyelocytic leukemia (PML) protein and its nuclear bodies (NBs) are implicated in intrinsic antiviral immunity against RNA viruses.
- PML localization to NBs requires conjugation with the small ubiquitin-like modifier (SUMO).
- PML-deficient mice show increased susceptibility to vesicular stomatitis virus (VSV) and rabies virus infections.
Purpose of the Study:
- To investigate the isoform-specific antiviral functions of PML.
- To determine the role of SUMOylation in PML's antiviral activity.
- To elucidate the mechanism underlying PML's antiviral effects.
Main Methods:
- Expression of different PML isoforms in cells.
- Assessment of viral replication inhibition (mRNA and protein synthesis).
- Mutation of SUMOylation sites (PMLIV 3KR) to assess functional requirement.
Main Results:
- PML isoform IV (PMLIV) and PMLIVa significantly inhibited viral mRNA and protein synthesis, reducing viral replication.
- Other PML isoforms (PMLI-VI) and PMLVIIb did not impair viral production.
- The antiviral activity of PMLIV was dependent on SUMOylation, as the PMLIV 3KR mutant lacked this function.
Conclusions:
- PMLIV and PMLIVa possess a specific antiviral function against RNA viruses, distinct from other PML isoforms.
- SUMOylation of PMLIV is essential for its antiviral activity.
- PMLIV may exert its antiviral function through interactions with nuclear body protein partners via its C-terminal region.
Related Concept Videos
01:28Rabies
01:14Rab Proteins
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
01:29Respiratory Syncytial Virus Disease