Exploring HIV-1 Maturation: A New Frontier in Antiviral Development DOI Creative Commons
Aidan McGraw,

Grace Hillmer,

Stefania M. Medehincu

et al.

Viruses, Journal Year: 2024, Volume and Issue: 16(9), P. 1423 - 1423

Published: Sept. 6, 2024

HIV-1 virion maturation is an essential step in the viral replication cycle to produce infectious virus particles. Gag and Gag-Pol polyproteins are assembled at plasma membrane of virus-producer cells bud from it extracellular compartment. The newly released progeny virions initially immature noninfectious. However, once polyprotein cleaved by protease virions, mature capsid proteins assemble form fullerene core. This core, harboring two copies genomic RNA, transforms morphology into morphological transformation referred as maturation. Virion influences distribution Env glycoprotein on surface induces conformational changes necessary for subsequent interaction with CD4 receptor. Several host factors, including like cyclophilin A, metabolites such IP6, lipid rafts containing sphingomyelins, have been demonstrated influence review article delves processes recruitment, emphasis role cell factors environmental conditions. Additionally, we discuss microscopic technologies assessing development current antivirals specifically targeting this critical replication, offering long-acting therapeutic options.

Language: Английский

The role of weak interactions in evaluation of inhibitory potential of Indinavir as an HIV protease inhibitor and its comparison with innovative drug candidates DOI
Mehdi Yoosefian, Hanieh Sabaghian

Computers in Biology and Medicine, Journal Year: 2025, Volume and Issue: 187, P. 109675 - 109675

Published: Jan. 28, 2025

Language: Английский

Citations

0
Considerations for capsid-targeting antiretrovirals in pre-exposure prophylaxis DOI
William M. McFadden,

Mia Færch,

Karen A. Kirby

et al.

Trends in Molecular Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

0
High-Yield and Quantitative Purification Method for HIV Which Minimizes Forces Applied to Virions Utilized to Investigate Maturation of HIV-1 via Cryo-Electron Tomography DOI Creative Commons
Benjamin Preece,

Wiley Peppel,

Rodrigo Gallegos

et al.

Viruses, Journal Year: 2025, Volume and Issue: 17(3), P. 364 - 364

Published: March 3, 2025

HIV is a lentivirus characterized by its cone shaped mature core. Visualization and structural examination of requires the purification virions to high concentrations. The yield integrity these are crucial for ensuring uniform representation all viral particles in subsequent analyses. In this study, we present method which minimizes forces applied while maximizing efficiency collection. This method, relies on virion sedimentation simulations, allows us capture between 1000 5000 released from individual HEK293 cells after transfection with NL4.3 backbone. We utilized approach investigate core formation several constructs: pNL4-3(RT:D185A&D186A) an inactive reverse transcriptase, NL4.3(IN: V165A&R166A) type-II integrase mutation, NL4.3(Ψ: Δ(105–278)&Δ(301–332)) featuring edited Ψ packaging signal. Notably, displayed mixed population, comprising immature virions, empty cores, cores detectable internal density. Conversely, derived exhibited type II mutant phenotype RNP density localized around consistent previous studies. contrast, containing suggest that simulations developed study can facilitate characterization enveloped viruses.

Language: Английский

Citations

0
Structural maturation of the matrix lattice is not required for HIV-1 particle infectivity DOI Creative Commons
Long Chen, Yuta Hikichi, Juan S. Rey

et al.

Science Advances, Journal Year: 2025, Volume and Issue: 11(19)

Published: May 9, 2025

During HIV-1 maturation, the matrix (MA) lattice underlying viral membrane undergoes a structural rearrangement, and newly released capsid (CA) protein forms mature CA. While it is well established that CA formation essential for particle infectivity, functional role of MA maturation remains unclear. Here, we examine an triple mutant, L20K/E73K/A82T, which, despite replicating similarly to wild-type (WT) in some cell lines, exhibits distinct biochemical behaviors suggest altered MA-MA interactions. Cryo–electron tomography with subtomogram averaging reveals that, although immature L20K/E73K/A82T virions closely resembles WT, lack detectable lattice. All-atom molecular dynamics simulations this absence results from destabilized inter-trimer interactions mutant virions. These findings ordered, membrane-associated not providing insights into requirements generation infectious particles.

Language: Английский

Citations

0
Exploring HIV-1 Maturation: A New Frontier in Antiviral Development DOI Creative Commons
Aidan McGraw,

Grace Hillmer,

Stefania M. Medehincu

et al.

Viruses, Journal Year: 2024, Volume and Issue: 16(9), P. 1423 - 1423

Published: Sept. 6, 2024

HIV-1 virion maturation is an essential step in the viral replication cycle to produce infectious virus particles. Gag and Gag-Pol polyproteins are assembled at plasma membrane of virus-producer cells bud from it extracellular compartment. The newly released progeny virions initially immature noninfectious. However, once polyprotein cleaved by protease virions, mature capsid proteins assemble form fullerene core. This core, harboring two copies genomic RNA, transforms morphology into morphological transformation referred as maturation. Virion influences distribution Env glycoprotein on surface induces conformational changes necessary for subsequent interaction with CD4 receptor. Several host factors, including like cyclophilin A, metabolites such IP6, lipid rafts containing sphingomyelins, have been demonstrated influence review article delves processes recruitment, emphasis role cell factors environmental conditions. Additionally, we discuss microscopic technologies assessing development current antivirals specifically targeting this critical replication, offering long-acting therapeutic options.

Language: Английский

Citations

3