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The N-Terminus of Murine Leukaemia Virus p12 Protein Is Required for Mature Core Stability
All retroviral genomes contain a gag gene that codes for the Gag polyprotein. Gag is cleaved upon viral maturation to release individual proteins, including matrix, capsid and nucleocapsid, providing the structural components of the virion. In murine leukaemia virus (MLV), Gag cleavage releases an additional protein, named p12, required for both early and late stages of the viral life cycle. The role of p12 during early events is poorly understood, and it is the only MLV protein without a function-associated name. Here, we show that p12 binds to the capsid shell of the viral core and stabilises it. Mutations that give rise to N-terminally altered p12 proteins result in a rapid loss of both p12 and capsid from viral cores, leading to abnormal core morphologies and abolishing the ability of particles to abrogate restriction by cellular factors that target viral capsid lattices. Understanding how the mature retroviral core forms and how it disassembles during infection is important as this determines the infectivity of all retroviruses, including HIV-1. Furthermore, altering core stability has recently become a novel target for HIV-1 therapeutics.
Vyšlo v časopise: The N-Terminus of Murine Leukaemia Virus p12 Protein Is Required for Mature Core Stability. PLoS Pathog 10(10): e32767. doi:10.1371/journal.ppat.1004474
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004474Souhrn
All retroviral genomes contain a gag gene that codes for the Gag polyprotein. Gag is cleaved upon viral maturation to release individual proteins, including matrix, capsid and nucleocapsid, providing the structural components of the virion. In murine leukaemia virus (MLV), Gag cleavage releases an additional protein, named p12, required for both early and late stages of the viral life cycle. The role of p12 during early events is poorly understood, and it is the only MLV protein without a function-associated name. Here, we show that p12 binds to the capsid shell of the viral core and stabilises it. Mutations that give rise to N-terminally altered p12 proteins result in a rapid loss of both p12 and capsid from viral cores, leading to abnormal core morphologies and abolishing the ability of particles to abrogate restriction by cellular factors that target viral capsid lattices. Understanding how the mature retroviral core forms and how it disassembles during infection is important as this determines the infectivity of all retroviruses, including HIV-1. Furthermore, altering core stability has recently become a novel target for HIV-1 therapeutics.
Zdroje
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