Intracellular HIV-1 Gag localization is impaired by mutations in the nucleocapsid zinc fingersReport as inadecuate




Intracellular HIV-1 Gag localization is impaired by mutations in the nucleocapsid zinc fingers - Download this document for free, or read online. Document in PDF available to download.

Retrovirology

, 4:54

First Online: 03 August 2007Received: 04 May 2007Accepted: 03 August 2007

Abstract

BackgroundThe 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.

ResultsWe 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.

ConclusionThese 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.

Electronic supplementary materialThe online version of this article doi:10.1186-1742-4690-4-54 contains supplementary material, which is available to authorized users.

Boyan Grigorov, Didier Décimo contributed equally to this work.

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Author: Boyan Grigorov - Didier Décimo - Fatima Smagulova - Christine Péchoux - Marylène Mougel - Delphine Muriaux - Jean-Luc Da

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