%0 Journal Article
%T VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability
%A Sonia Brun
%A Maxime Solignat
%A Bernard Gay
%A Eric Bernard
%A Laurent Chaloin
%A David Fenard
%A Christian Devaux
%A Nathalie Chazal
%A Laurence Briant
%J Retrovirology
%D 2008
%I BioMed Central
%R 10.1186/1742-4690-5-57
%X Here, we show that infectivity of HIV-1 mutants bearing S149A and S178A mutations in CA can be efficiently restored when pseudotyped with vesicular stomatitis virus envelope glycoprotein, that addresses the mutant cores through the endocytic pathway rather than by fusion at the plasma membrane. The mechanisms by which these mutations disrupt virus infectivity were investigated. S149A and S178A mutants were unable to complete reverse transcription and/or produce 2-LTR DNA. Morphological analysis of viral particles and in vitro uncoating assays of isolated cores demonstrated that infectivity defects resulted from disruption of the viral core assembly and stability for S149A and S178A mutants, respectively. Consistent with these results, both mutants failed to saturate TRIM-antiviral restriction activity.Defects generated at the level of core assembly and stability by S149A and S178A mutations are sensitive to the way of delivery of viral nucleoprotein complexes into the target cell. Addressing CA mutants through the endocytic pathway may compensate for defects generated at the reverse transcription/nuclear import level subsequent to impairment of core assembly or stability.The genome of the human immunodeficiency virus type 1 (HIV-1) is packaged within a conical shaped core formed by the viral capsid protein (CA) and delivered to the host cell cytoplasm upon fusion of the viral and cell membranes. Establishment of viral replication then requires the genomic RNA to be reverse transcribed into a double stranded proviral DNA. Upon completion of the reverse transcription (RT), full-length HIV-1 DNA associates into a functional pre-integration complex imported through the nuclear pore before integration into the host chromosome. Completion of HIV-1 RT appears to be a timely regulated process. Indeed, HIV-1 DNA synthesis is limited in intact viral core particles where late RT products are less efficiently synthesized than early DNA intermediates [1,2]. The synthesis of a co
%U http://www.retrovirology.com/content/5/1/57