4.8 Article

Cargo Release from Nonenveloped Viruses and Virus-like Nanoparticles: Capsid Rupture or Pore Formation

期刊

ACS NANO
卷 15, 期 12, 页码 19233-19243

出版社

AMER CHEMICAL SOC
DOI: 10.1021/acsnano.1c04814

关键词

virus-like nanoparticles; RNA virus; genome release; capsid; computer simulations; coarse-grained model; cryo-EM

资金

  1. Czech Science Foundation [GX19-25982X, GA20-20152S]
  2. MEYS CR via the LL2007 project under the ERC CZ program
  3. CESNET under the program Projects of Large Research, Development, and Innovations Infrastructures [LM2015042]
  4. CERIT Scientific Cloud under the program Projects of Large Research, Development, and Innovations Infrastructures [LM2015085]
  5. MEYS CR from the Large Infrastructures for Research, Experimental Development and Innovations [LM2015070]
  6. MEYS CR [LM2018127]

向作者/读者索取更多资源

Virus-like nanoparticles and wild-type viruses share similar protein shells and aims of delivering genes into cells, but the mechanism of gene release differs. Interactions between capsid subunits and compactness of genes affect the speed and pathways of release, providing insights for drug delivery design.
Virus-like nanoparticles are protein shells similar to wild-type viruses, and both aim to deliver their content into a cell. Unfortunately, the release mechanism of their cargo/genome remains elusive. Pores on the symmetry axes were proposed to enable the slow release of the viral genome. In contrast, cryo-EM images showed that capsids of nonenveloped RNA viruses can crack open and rapidly release the genome. We combined in vitro cryo-EM observations of the genome release of three viruses with coarse-grained simulations of generic virus-like nanoparticles to investigate the cargo/genome release pathways. Simulations provided details on both slow and rapid release pathways, including the success rates of individual releases. Moreover, the simulated structures from the rapid release pathway were in agreement with the experiment. Slow release occurred when interactions between capsid subunits were long-ranged, and the cargo/genome was noncompact. In contrast, rapid release was preferred when the interaction range was short and/or the cargo/genome was compact. These findings indicate a design strategy of virus-like nanoparticles for drug delivery.

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