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Peer-reviewedCC BY-NC 4.0PNAS Nexus

Viral capsid-membrane interactions propel non-Brownian movements of nonenveloped reoviruses during entry

  • Mengchi Jiao1
  • Gregory R Cantrall2
  • Yanqi Yu1
  • Anthony J Snyder3
  • Steven M Abel2
  • Pranav Danthi3
  • Yan Yu4,5
5 affiliations
  1. 1Department of Chemistry, Indiana University , Bloomington, IN 47405-7102 ,
  2. 2Department of Chemical and Biomolecular Engineering, University of Tennessee , Knoxville, TN 37996 ,
  3. 3Department of Biology, Indiana University , Bloomington, IN 47405-7102 ,
  4. 4Department of Chemistry, Washington University in St. Louis , St. Louis, MO 63130 ,
  5. 5Department of Biomedical Engineering, Washington University in St. Louis , St. Louis, MO 63130 ,
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Abstract

Understanding how nonenveloped viruses breach host cell membranes is critical for developing strategies to block viral entry, a key step in infection. Despite extensive study, how viral capsids and host lipid membranes dynamically cooperate during membrane penetration remains poorly defined. Here, using reovirus as a model nonenveloped virus and planar model membranes, we identify previously unrecognized non-Brownian membrane motions of infectious subvirion particles (ISVPs) by single-virus tracking. We then integrate experiments with computational modeling to dissect the stepwise, processive capsid–membrane interactions encoded in these distinct dynamics. We show that ISVP motion transitions from an initial phase of directed translocation to progressively confined diffusion. This behavior is consistent with a multistep entry mechanism in which initial capsid–membrane contact triggers release of the membrane-active μ1N peptide. Together, our data and simulations support a model in which membrane-inserted μ1N may accumulate locally to create retention sites that promote further virus adsorption and progressively restrict particle mobility. By directly visualizing these motion signatures, we resolve transient and cooperative capsid–membrane interactions that are difficult to capture using conventional biochemical approaches. Together, these findings provide new insight into early membrane penetration events of nonenveloped viruses.

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Cite

BibTeXRIS
BibTeX
@article{jiao2026viral,
  title = {{Viral capsid-membrane interactions propel non-Brownian movements of nonenveloped reoviruses during entry}},
  author = {Mengchi Jiao and Gregory R Cantrall and Yanqi Yu and Anthony J Snyder and Steven M Abel and Pranav Danthi and Yan Yu},
  journal = {PNAS Nexus},
  year = {2026},
  month = oct,
  doi = {10.1093/pnasnexus/pgag350},
  url = {https://academic.oup.com/pnasnexus/article/doi/10.1093/pnasnexus/pgag350/8892655},
  note = {CC BY-NC 4.0},
}
RIS
TY  - JOUR
TI  - Viral capsid-membrane interactions propel non-Brownian movements of nonenveloped reoviruses during entry
AU  - Mengchi Jiao
AU  - Gregory R Cantrall
AU  - Yanqi Yu
AU  - Anthony J Snyder
AU  - Steven M Abel
AU  - Pranav Danthi
AU  - Yan Yu
PY  - 2026
DA  - 2026/10/09
JO  - PNAS Nexus
DO  - 10.1093/pnasnexus/pgag350
UR  - https://academic.oup.com/pnasnexus/article/doi/10.1093/pnasnexus/pgag350/8892655
AB  - Understanding how nonenveloped viruses breach host cell membranes is critical for developing strategies to block viral entry, a key step in infection. Despite extensive study, how viral capsids and host lipid membranes dynamically cooperate during membrane penetration remains poorly defined. Here, using reovirus as a model nonenveloped virus and planar model membranes, we identify previously unrecognized non-Brownian membrane motions of infectious subvirion particles (ISVPs) by single-virus tracking. We then integrate experiments with computational modeling to dissect the stepwise, processive capsid–membrane interactions encoded in these distinct dynamics. We show that ISVP motion transitions from an initial phase of directed translocation to progressively confined diffusion. This behavior is consistent with a multistep entry mechanism in which initial capsid–membrane contact triggers release of the membrane-active μ1N peptide. Together, our data and simulations support a model in which membrane-inserted μ1N may accumulate locally to create retention sites that promote further virus adsorption and progressively restrict particle mobility. By directly visualizing these motion signatures, we resolve transient and cooperative capsid–membrane interactions that are difficult to capture using conventional biochemical approaches. Together, these findings provide new insight into early membrane penetration events of nonenveloped viruses.
SN  - 2752-6542
ER  -