Elucidating the Mechanisms of Genome Release in Picornaviruses
using Cryo-EM and Coarse-Grained Simulations

a 2023

Elucidating the Mechanisms of Genome Release in Picornaviruses using Cryo-EM and Coarse-Grained Simulations

SUKENÍK, Lukáš; Liya MUKHAMEDOVA; Michaela PROCHÁZKOVÁ; Karel ŠKUBNÍK; Pavel PLEVKA et. al.

Základní údaje

Originální název

Elucidating the Mechanisms of Genome Release in Picornaviruses using Cryo-EM and Coarse-Grained Simulations

Název česky

Objasnění mechanismů uvolnění genomu u pikonavirů pomocí Kryo-EM a "Coarse-Grained" simulací

Autoři

SUKENÍK, Lukáš (203 Česká republika, domácí); Liya MUKHAMEDOVA (643 Rusko, domácí); Michaela PROCHÁZKOVÁ (203 Česká republika, domácí); Karel ŠKUBNÍK (203 Česká republika, domácí); Pavel PLEVKA (203 Česká republika, domácí) a Robert VÁCHA (203 Česká republika, garant, domácí)

Vydání

EBSA Congress 2023, 2023

Další údaje

Jazyk

angličtina

Typ výsledku

Konferenční abstrakt

Obor

10607 Virology

Stát vydavatele

Švédsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Kód RIV

RIV/00216224:14740/23:00132208

Organizační jednotka

Středoevropský technologický institut

Klíčová slova česky

pikonaviry; uvolnění genomu; KryoEM; simulace; nanočástice podobné virům

Klíčová slova anglicky

piconaviruses; genome release; cryoEM; coarse grained simulation; virus like particles

Štítky

NIVB_CEITEC, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 6. 3. 2024 09:10, Mgr. Eva Dubská

Anotace

V originále

Genome release is a crucial step in the life cycle of picornaviruses. During virus intracellular transport in endosomes, exposure to low pH triggers a conformational change in the capsid necessary for genome release. As a result, some viruses form pores on symmetry axes, which have been proposed to facilitate slow release of the viral genome. In contrast, recent cryo-EM images have shown that viral capsids can crack open and release the genome rapidly. Thus, the mechanism of genome release remains elusive. We combined in vitro cryo-EM observations of the genome release from four viruses with coarse-grained simulations of generic virus-like nanoparticles to investigate the release pathways and virion stability. Here we show how the nature of interactions between capsid building blocks determines virion stability and genome release pathway. We found that preformed pores at the symmetry axes were not necessary for slow genome release. Rather, slow release occurred through transient pores when interactions between capsid subunits were long-range, and the interactions within the genome were weak. In contrast, rapid release was preferred when capsid interactions were short-range and/or the genome interactions were strong. These findings elucidate the genome release behavior of viruses and suggest a design strategy for virus-like nanoparticles for drug delivery.

Návaznosti

LX22NPO5103, projekt VaV

Název: Národní institut virologie a bakteriologie (Akronym: NIVB)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Národní institut virologie a bakteriologie, 5.1 EXCELES

Přiložené soubory

Sukenik__L._EBSA2023.pdf

Citovat

SUKENÍK, Lukáš; Liya MUKHAMEDOVA; Michaela PROCHÁZKOVÁ; Karel ŠKUBNÍK; Pavel PLEVKA a Robert VÁCHA. Elucidating the Mechanisms of Genome Release in Picornaviruses using Cryo-EM and Coarse-Grained Simulations. In EBSA Congress 2023. 2023.

@proceedings{2337319,
   author = {Sukeník, Lukáš and Mukhamedova, Liya and Procházková, Michaela and Škubník, Karel and Plevka, Pavel and Vácha, Robert},
   booktitle = {EBSA Congress 2023},
   keywords = {piconaviruses; genome release; cryoEM; coarse grained simulation; virus like particles},
   language = {eng},
   title = {Elucidating the Mechanisms of Genome Release in Picornaviruses using Cryo-EM and Coarse-Grained Simulations},
   url = {https://mkon.nu/ebsa/scientific_program},
   year = {2023}
}

TY  - CONF
ID  - 2337319
AU  - Sukeník, Lukáš - Mukhamedova, Liya - Procházková, Michaela - Škubník, Karel - Plevka, Pavel - Vácha, Robert
PY  - 2023
TI  - Elucidating the Mechanisms of Genome Release in Picornaviruses using Cryo-EM and Coarse-Grained Simulations
KW  - piconaviruses
KW  - genome release
KW  - cryoEM
KW  - coarse grained simulation
KW  - virus like particles
UR  - https://mkon.nu/ebsa/scientific_program
N2  - Genome release is a crucial step in the life cycle of picornaviruses. During virus intracellular transport in endosomes, exposure to low pH triggers a conformational change in the capsid necessary for genome release. As a result, some viruses form pores on symmetry axes, which have been proposed to facilitate slow release of the viral genome. In contrast, recent cryo-EM images have shown that viral capsids can crack open and release the genome rapidly. Thus, the mechanism of genome release remains elusive. We combined in vitro cryo-EM observations of the genome release from four viruses with coarse-grained simulations of generic virus-like nanoparticles to investigate the release pathways and virion stability. Here we show how the nature of interactions between capsid building blocks determines virion stability and genome release pathway. We found that preformed pores at the symmetry axes were not necessary for slow genome release. Rather, slow release occurred through transient pores when interactions between capsid subunits were long-range, and the interactions within the genome were weak. In contrast, rapid release was preferred when capsid interactions were short-range and/or the genome interactions were strong. These findings elucidate the genome release behavior of viruses and suggest a design strategy for virus-like nanoparticles for drug delivery.
ER  -

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