Role of the Psi Packaging Signal and Dimerization Initiation Sequence in the Organization of Rous Sarcoma Virus Gag-gRNA Co-Condensates

Retroviral genome selection and virion assembly remain promising targets for novel therapeutic intervention. Recent studies have demonstrated that the Gag proteins of Rous sarcoma virus (RSV) and human immunodeficiency virus type-1 (HIV-1) undergo nuclear trafficking, colocalize with nascent genomic...

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Main Authors: Gregory S. Lambert, Rebecca J. Kaddis Maldonado, Leslie J. Parent
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Viruses
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Online Access:https://www.mdpi.com/1999-4915/17/1/97
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author Gregory S. Lambert
Rebecca J. Kaddis Maldonado
Leslie J. Parent
author_facet Gregory S. Lambert
Rebecca J. Kaddis Maldonado
Leslie J. Parent
author_sort Gregory S. Lambert
collection DOAJ
description Retroviral genome selection and virion assembly remain promising targets for novel therapeutic intervention. Recent studies have demonstrated that the Gag proteins of Rous sarcoma virus (RSV) and human immunodeficiency virus type-1 (HIV-1) undergo nuclear trafficking, colocalize with nascent genomic viral RNA (gRNA) at transcription sites, may interact with host transcription factors, and display biophysical properties characteristic of biomolecular condensates. In the present work, we utilized a controlled in vitro condensate assay and advanced imaging approaches to investigate the effects of interactions between RSV Gag condensates and viral and nonviral RNAs on condensate abundance and organization. We observed that the psi (Ψ) packaging signal and the dimerization initiation sequence (DIS) had stabilizing effects on RSV Gag condensates, while RNAs lacking these features promoted or antagonized condensation, depending on local protein concentration and condensate architecture. An RNA containing Ψ, DIS, and the dimerization linkage structure (DLS) that is capable of stable dimer formation was observed to act as a bridge between RSV Gag condensates. These observations suggest additional, condensate-related roles for Gag-Ψ binding, gRNA dimerization, and Gag dimerization/multimerization in gRNA selection and packaging, representing a significant step forward in our understanding of how these interactions collectively facilitate efficient genome packaging.
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spelling doaj-art-eaeed2bba2814512977cae696d2377ec2025-01-24T13:52:35ZengMDPI AGViruses1999-49152025-01-011719710.3390/v17010097Role of the Psi Packaging Signal and Dimerization Initiation Sequence in the Organization of Rous Sarcoma Virus Gag-gRNA Co-CondensatesGregory S. Lambert0Rebecca J. Kaddis Maldonado1Leslie J. Parent2Department of Medicine, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, USADepartment of Medicine, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, USADepartment of Medicine, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, USARetroviral genome selection and virion assembly remain promising targets for novel therapeutic intervention. Recent studies have demonstrated that the Gag proteins of Rous sarcoma virus (RSV) and human immunodeficiency virus type-1 (HIV-1) undergo nuclear trafficking, colocalize with nascent genomic viral RNA (gRNA) at transcription sites, may interact with host transcription factors, and display biophysical properties characteristic of biomolecular condensates. In the present work, we utilized a controlled in vitro condensate assay and advanced imaging approaches to investigate the effects of interactions between RSV Gag condensates and viral and nonviral RNAs on condensate abundance and organization. We observed that the psi (Ψ) packaging signal and the dimerization initiation sequence (DIS) had stabilizing effects on RSV Gag condensates, while RNAs lacking these features promoted or antagonized condensation, depending on local protein concentration and condensate architecture. An RNA containing Ψ, DIS, and the dimerization linkage structure (DLS) that is capable of stable dimer formation was observed to act as a bridge between RSV Gag condensates. These observations suggest additional, condensate-related roles for Gag-Ψ binding, gRNA dimerization, and Gag dimerization/multimerization in gRNA selection and packaging, representing a significant step forward in our understanding of how these interactions collectively facilitate efficient genome packaging.https://www.mdpi.com/1999-4915/17/1/97retrovirusesRous sarcoma virusbiomolecular condensatesgenome selectiondimerization
spellingShingle Gregory S. Lambert
Rebecca J. Kaddis Maldonado
Leslie J. Parent
Role of the Psi Packaging Signal and Dimerization Initiation Sequence in the Organization of Rous Sarcoma Virus Gag-gRNA Co-Condensates
Viruses
retroviruses
Rous sarcoma virus
biomolecular condensates
genome selection
dimerization
title Role of the Psi Packaging Signal and Dimerization Initiation Sequence in the Organization of Rous Sarcoma Virus Gag-gRNA Co-Condensates
title_full Role of the Psi Packaging Signal and Dimerization Initiation Sequence in the Organization of Rous Sarcoma Virus Gag-gRNA Co-Condensates
title_fullStr Role of the Psi Packaging Signal and Dimerization Initiation Sequence in the Organization of Rous Sarcoma Virus Gag-gRNA Co-Condensates
title_full_unstemmed Role of the Psi Packaging Signal and Dimerization Initiation Sequence in the Organization of Rous Sarcoma Virus Gag-gRNA Co-Condensates
title_short Role of the Psi Packaging Signal and Dimerization Initiation Sequence in the Organization of Rous Sarcoma Virus Gag-gRNA Co-Condensates
title_sort role of the psi packaging signal and dimerization initiation sequence in the organization of rous sarcoma virus gag grna co condensates
topic retroviruses
Rous sarcoma virus
biomolecular condensates
genome selection
dimerization
url https://www.mdpi.com/1999-4915/17/1/97
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