Session 4Oral Abstract Presentations HIV Replication: Entry and Assembly Session Day and Time: Tuesday 10 am - 12:30 pm Presentation Time: 12:15 Room: Ballroom A
26lb PML and the Proteasome as Mediators of Intracellular Antiretroviral Innate Immunity P. Turelli, D. Trono* Univ of Geneva, Geneva, Switzerland
Background: Mammalian cells have evolved mechanisms that limit their susceptibility to viral infections. We previously demonstrated that the nuclear protein PML interferes with the immediate early steps of HIV replication. Here, we asked whether this phenomenon represents a general protection of human cells against retroviral infections.
Methods: Using a combination of biochemical, morphological and functional analyses, we examined a putative role for PML in the so-called Ref-1 restriction that renders human cells resistant to infection with some strains of murine leukemia virus (MLV). We further investigated a possible involvement of the proteasome in these events.
Results: Immunoprecipitation studies performed during the early phase of MLV infection of human cells demonstrated an association between PML and the incoming preintegration complex of restricted (“N-tropic”) but not of non-restricted (“B-tropic”) MLV strains. Furthermore, the pharmacological knockdown of PML suppressed Ref-1 restriction. Finally, the use of proteasome inhibitors relieved PML-mediated Ref-1 restriction and partial resistance of human cells to HIV infection.
Conclusion: PML and the proteasome are the mediators of an intracellular innate antiviral response that limits the susceptibility of human cells to infection by HIV and certain oncoretroviruses. Because “N-tropic” and “B-tropic” MLV strains differ only by a few amino acids in Capsid (CA), it is likely that this retroviral constituent is targeted by this response in both HIV and MLV.
