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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 |
Appears in Collections: | Staff Publications Elements |
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