A 2.8-Angstrom-Resolution Cryo-Electron Microscopy Structure of
Human Parechovirus 3 in Complex with Fab from a Neutralizing
Antibody

J 2019

A 2.8-Angstrom-Resolution Cryo-Electron Microscopy Structure of Human Parechovirus 3 in Complex with Fab from a Neutralizing Antibody

DOMANSKA, Ausra, Justin W FLATT, Joonas J J JUKONEN, James A GERAETS, Sarah J BUTCHER et. al.

Základní údaje

Originální název

A 2.8-Angstrom-Resolution Cryo-Electron Microscopy Structure of Human Parechovirus 3 in Complex with Fab from a Neutralizing Antibody

Autoři

DOMANSKA, Ausra, Justin W FLATT, Joonas J J JUKONEN, James A GERAETS a Sarah J BUTCHER

Vydání

Journal of Virology, WASHINGTON, American Society for Microbiology, 2019, 0022-538X

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10607 Virology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 4.501

Organizační jednotka

CIISB

DOI

http://dx.doi.org/10.1128/JVI.01597-18

UT WoS

000457744600013

Klíčová slova anglicky

cryo-EM; genome packaging; human parechovirus 3; neutralizing antibodies; picornavirus

Štítky

CF CRYO

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 10. 6. 2024 16:22, Mgr. Eva Dubská

Anotace

V originále

Human parechovirus 3 (HPeV3) infection is associated with sepsis characterized by significant immune activation and subsequent tissue damage in neonates. Strategies to limit infection have been unsuccessful due to inadequate molecular diagnostic tools for early detection and the lack of a vaccine or specific antiviral therapy. Toward the latter, we present a 2.8-angstrom-resolution structure of HPeV3 in complex with fragments from a neutralizing human monoclonal antibody, AT12-015, using cryo-electron microscopy (cryo-EM) and image reconstruction. Modeling revealed that the epitope extends across neighboring asymmetric units with contributions from capsid proteins VP0, VP1, and VP3. Antibody decoration was found to block binding of HPeV3 to cultured cells. Additionally, at high resolution, it was possible to model a stretch of RNA inside the virion and, from this, identify the key features that drive and stabilize protein-RNA association during assembly.

Návaznosti

90043, velká výzkumná infrastruktura

Název: CIISB

Citovat

DOMANSKA, Ausra, Justin W FLATT, Joonas J J JUKONEN, James A GERAETS a Sarah J BUTCHER. A 2.8-Angstrom-Resolution Cryo-Electron Microscopy Structure of Human Parechovirus 3 in Complex with Fab from a Neutralizing Antibody. Journal of Virology. WASHINGTON: American Society for Microbiology, 2019, roč. 93, č. 4, 12 s. ISSN 0022-538X. Dostupné z: https://dx.doi.org/10.1128/JVI.01597-18.

@article{2409597,
   author = {Domanska, Ausra and Flatt, Justin W and Jukonen, Joonas J J and Geraets, James A and Butcher, Sarah J},
   article_location = {WASHINGTON},
   article_number = {4},
   doi = {http://dx.doi.org/10.1128/JVI.01597-18},
   keywords = {cryo-EM; genome packaging; human parechovirus 3; neutralizing antibodies; picornavirus},
   language = {eng},
   issn = {0022-538X},
   journal = {Journal of Virology},
   title = {A 2.8-Angstrom-Resolution Cryo-Electron Microscopy Structure of Human Parechovirus 3 in Complex with Fab from a Neutralizing Antibody},
   url = {https://www.pnas.org/doi/epdf/10.1073/pnas.1904732116},
   volume = {93},
   year = {2019}
}

TY  - JOUR
ID  - 2409597
AU  - Domanska, Ausra - Flatt, Justin W - Jukonen, Joonas J J - Geraets, James A - Butcher, Sarah J
PY  - 2019
TI  - A 2.8-Angstrom-Resolution Cryo-Electron Microscopy Structure of Human Parechovirus 3 in Complex with Fab from a Neutralizing Antibody
JF  - Journal of Virology
VL  - 93
IS  - 4
PB  - American Society for Microbiology
SN  - 0022538X
KW  - cryo-EM
KW  - genome packaging
KW  - human parechovirus 3
KW  - neutralizing antibodies
KW  - picornavirus
UR  - https://www.pnas.org/doi/epdf/10.1073/pnas.1904732116
N2  - Human parechovirus 3 (HPeV3) infection is associated with sepsis characterized by significant immune activation and subsequent tissue damage in neonates. Strategies to limit infection have been unsuccessful due to inadequate molecular diagnostic tools for early detection and the lack of a vaccine or specific antiviral therapy. Toward the latter, we present a 2.8-angstrom-resolution structure of HPeV3 in complex with fragments from a neutralizing human monoclonal antibody, AT12-015, using cryo-electron microscopy (cryo-EM) and image reconstruction. Modeling revealed that the epitope extends across neighboring asymmetric units with contributions from capsid proteins VP0, VP1, and VP3. Antibody decoration was found to block binding of HPeV3 to cultured cells. Additionally, at high resolution, it was possible to model a stretch of RNA inside the virion and, from this, identify the key features that drive and stabilize protein-RNA association during assembly.
ER  -

DOMANSKA, Ausra, Justin W FLATT, Joonas J J JUKONEN, James A GERAETS a Sarah J BUTCHER. A 2.8-Angstrom-Resolution Cryo-Electron Microscopy Structure of Human Parechovirus 3 in Complex with Fab from a Neutralizing Antibody. \textit{Journal of Virology}. WASHINGTON: American Society for Microbiology, 2019, roč.~93, č.~4, 12 s. ISSN~0022-538X. Dostupné z: https://dx.doi.org/10.1128/JVI.01597-18.

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