During the maturation step, the retroviral capsid proteins (CAs) assemble into polymorphic capsids. Their acute curvature is largely determined by 12 pentamers inserted into the hexameric lattice. However, how the CA switches its conformation to control assembly curvature remains unclear. We report the high-resolution structural model of the Rous sarcoma virus (RSV) CA = 1 capsid, established by molecular dynamics simulations combining solid-state NMR and prior cryoelectron tomography restraints. Comparing this with our previous model of the RSV CA tubular assembly, we identify the key residues for dictating the incorporation of acute curvatures. These residues undergo large torsion angle changes, resulting in a 34° rotation of the C-terminal domain relative to its N-terminal domain around the flexible interdomain linker, without substantial changes of either the conformation of individual domains or the assembly contact interfaces. This knowledge provides new insights to help decipher the mechanism of the retroviral capsid assembly.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9083439 | PMC |
| http://dx.doi.org/10.1021/acs.jpclett.1c01769 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Antiviral Agents: Structural Basis of Action and Rational Design.
Subcell Biochem
December 2024
Department of Biomedical Sciences, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain.
During the last forty years, significant progress has been made in the development of novel antiviral drugs, mainly crystallizing in the establishment of potent antiretroviral therapies and the approval of drugs eradicating hepatitis C virus infection. Although major targets of antiviral intervention involve intracellular processes required for the synthesis of viral proteins and nucleic acids, a number of inhibitors blocking virus assembly, budding, maturation, entry, or uncoating act on virions or viral capsids. In this review, we focus on the drug discovery process while presenting the currently used methodologies to identify novel antiviral drugs by means of computer-based approaches.
View Article and Find Full Text PDFDecoding the biogenesis of HIV-induced CPSF6 puncta and their fusion with the nuclear speckle.
bioRxiv
December 2024
Institut Pasteur, Advanced Molecular Virology Unit, Department of Virology, Université Paris Cité, 75015 Paris, France.
Viruses rely on host cellular machinery for replication. After entering the nucleus, the HIV genome accumulates in nuclear niches where it undergoes reverse transcription and integrates into neighboring chromatin, promoting high transcription rates and new virus progeny. Despite anti-retroviral treatment, viral genomes can persist in these nuclear niches and reactivate if treatment is interrupted, likely contributing to the formation of viral reservoirs.
View Article and Find Full Text PDFAnti-tembusu virus of capsid-targeted viral inactivation delivered by lentiviral vector in vivo.
Vet Microbiol
January 2025
Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Engineering Research Center of Southwest Animal Disease Prevention and Control Technology, Ministry of Education, Chengdu, Sichuan 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu, Sichuan 611130, China. Electronic address:
Tembusu virus (TMUV) is a member of genus flavivirus, which mainly causes decrease in production in egg ducks and neurological symptom in meatducks, causing serious economic losses to the poultry industry. Recently, the commercialized TMUV vaccines are mainly the WF100 live vaccine and the attenuated live vaccine (FX2010-180P), so it is particularly important to find new methods to combat TMUV. The capsid-targeted viral inactivation (CTVI) strategy is based on a viral core protein and an exogenous factor that can destroy viral DNA or RNA.
View Article and Find Full Text PDFIn vivo HIV-1 nuclear condensates safeguard against cGAS and license reverse transcription.
EMBO J
January 2025
Institut Pasteur, Advanced Molecular Virology Unit, Department of Virology, Université Paris Cité, 75015, Paris, France.
Entry of viral capsids into the nucleus induces the formation of biomolecular condensates called HIV-1 membraneless organelles (HIV-1-MLOs). Several questions remain about their persistence, in vivo formation, composition, and function. Our study reveals that HIV-1-MLOs persisted for several weeks in infected cells, and their abundance correlated with viral infectivity.
View Article and Find Full Text PDFDeterminants in the HTLV-1 Capsid Major Homology Region that are Critical for Virus Particle Assembly.
J Mol Biol
December 2024
Institute for Molecular Virology, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA; Department of Diagnostic and Biological Sciences, School of Dentistry, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA; Biochemistry, Molecular Biology & Biophysics Graduate Program, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA; Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA; Department of Microbiology and Immunology, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA. Electronic address:
The Gag protein of retroviruses is the primary driver of virus particle assembly. Particle morphologies among retroviral genera are distinct, with intriguing differences observed relative to human immunodeficiency virus type 1 (HIV-1), particularly that of human T-cell leukemia virus type 1 (HTLV-1). In contrast to HIV-1 and other retroviruses where the capsid (CA) carboxy-terminal domain (CTD) possesses the key amino acid determinants involved in driving Gag-Gag interactions, we have previously demonstrated that the amino-terminal domain (NTD) encodes the key residues crucial for Gag multimerization and immature particle production.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!