Please use this identifier to cite or link to this item: https://doi.org/10.1128/JVI.00124-12
Title: HIV-2 genome dimerization is required for the correct processing of gag: A second-site reversion in matrix can restore both processes in dimerization-impaired mutant viruses
Authors: L'Hernault, A
Weiss, E.U
Greatorex, J.S
Lever, A.M 
Keywords: Gag protein
matrix protein
mutant protein
purine
stem loop 1 protein
unclassified drug
virus protein
virus RNA
article
controlled study
genetic analysis
genetic parameters
genome dimerization
human
human cell
Human immunodeficiency virus 1
Human immunodeficiency virus 2
packaging signal
priority journal
protein assembly
protein motif
protein processing
protein structure
revertant
viral phenomena and functions
virus examination
virus infectivity
virus mutant
virus replication
Amino Acid Motifs
Cell Line
Dimerization
gag Gene Products, Human Immunodeficiency Virus
Genome, Viral
HIV Infections
HIV-2
Humans
Inverted Repeat Sequences
Molecular Sequence Data
Mutation
Nucleic Acid Conformation
Protein Processing, Post-Translational
Virus Replication
Human immunodeficiency virus 1
Human immunodeficiency virus 2
Issue Date: 2012
Citation: L'Hernault, A, Weiss, E.U, Greatorex, J.S, Lever, A.M (2012). HIV-2 genome dimerization is required for the correct processing of gag: A second-site reversion in matrix can restore both processes in dimerization-impaired mutant viruses. Journal of Virology 86 (10) : 5867-5876. ScholarBank@NUS Repository. https://doi.org/10.1128/JVI.00124-12
Rights: Attribution 4.0 International
Abstract: A unique feature of retroviruses is the packaging of two copies of their genome, noncovalently linked at their 5' ends. In vitro, dimerization of human immunodeficiency virus type 2 (HIV-2) RNA occurs by interaction of a self-complementary sequence exposed in the loop of stem-loop 1 (SL-1), also termed the dimer initiation site (DIS). However, in virions, HIV-2 genome dimerization does not depend on the DIS. Instead, a palindrome located within the packaging signal (Psi) is the essential motif for genome dimerization. We reported previously that a mutation within Psi decreasing genome dimerization and packaging also resulted in a reduced proportion of mature particles (A. L'Hernault, J. S. Greatorex, R. A. Crowther, and A. M. Lever, Retrovirology 4:90, 2007). In this study, we investigated further the relationship between HIV-2 genome dimerization, particle maturation, and infectivity by using a series of targeted mutations in SL-1. Our results show that disruption of a purine-rich (392-GGAG-395) motif within Psi causes a severe reduction in genome dimerization and a replication defect. Maintaining the extended SL-1 structure in combination with the 392-GGAG-395 motif enhanced packaging. Unlike that of HIV-1, which can replicate despite mutation of the DIS, HIV-2 replication depends critically on genome dimerization rather than just packaging efficiency. Gag processing was altered in the HIV-2 dimerization mutants, resulting in the accumulation of the MA-CA-p2 processing intermediate and suggesting a link between genome dimerization and particle assembly. Analysis of revertant SL-1 mutant viruses revealed that a compensatory mutation in matrix (70TI) could rescue viral replication and partially restore genome dimerization and Gag processing. Our results are consistent with interdependence between HIV-2 RNA dimerization and the correct proteolytic cleavage of the Gag polyprotein. © 2012, American Society for Microbiology.
Source Title: Journal of Virology
URI: https://scholarbank.nus.edu.sg/handle/10635/180837
ISSN: 0022-538X
DOI: 10.1128/JVI.00124-12
Rights: Attribution 4.0 International
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