Intracellular HIV-1 Gag localization is impaired by mutations in the nucleocapsid zinc fingers.

Boyan Grigorov (1) , Didier Decimo (1) , Fatima Smagulova (2) , Christine Péchoux (3) , Marylène Mougel (2) , Delphine Muriaux (1) , Jean-Luc Darlix (1)

1 Virologie humaine
2 IRIM - Institut de Recherche en Infectiologie de Montpellier
3 GPL - Unité de recherche génomique et physiologie de la lactation

BACKGROUND: The HIV-1 nucleocapsid protein (NC) is formed of two CCHC zinc fingers flanked by highly basic regions. HIV-1 NC plays key roles in virus structure and replication via its nucleic acid binding and chaperoning properties. In fact, NC controls proviral DNA synthesis by reverse transcriptase (RT), gRNA dimerization and packaging, and virion assembly. RESULTS: We previously reported a role for the first NC zinc finger in virion structure and replication 1. To investigate the role of both NC zinc fingers in intracellular Gag trafficking, and in virion assembly, we generated series of NC zinc fingers mutations. Results show that all Zinc finger mutations have a negative impact on virion biogenesis and maturation and rendered defective the mutant viruses. The NC zinc finger mutations caused an intracellular accumulation of Gag, which was found either diffuse in the cytoplasm or at the plasma membrane but not associated with endosomal membranes as for wild type Gag. Evidences are also provided showing that the intracellular interactions between NC-mutated Gag and the gRNA were impaired. CONCLUSION: These results show that Gag oligomerization mediated by gRNA-NC interactions is required for correct Gag trafficking, and assembly in HIV-1 producing cells and the release of infectious viruses.

Mots clés: Humans; Protein Binding; RNA; Guide; Virus Assembly; Zinc Fingers; gag Gene Products; Human Immunodeficiency Virus; Tumor; Cytoplasm; Endosomes; Gene Products; gag; HIV Core Protein p24; HIV-1

Mots clés: Cell Line; Cell Membrane; Mutation

Domaines: Biologie cellulaire

Boyan Grigorov, Didier Decimo, Fatima Smagulova, Christine Péchoux, Marylène Mougel, et al.. Intracellular HIV-1 Gag localization is impaired by mutations in the nucleocapsid zinc fingers.. Retrovirology, 2007, 4, pp.54. ⟨10.1186/1742-4690-4-54⟩. ⟨hal-00258941⟩