Obstruction of Dengue Virus Maturation by Fab Fragments of the
2H2 Antibody

J 2013

Obstruction of Dengue Virus Maturation by Fab Fragments of the 2H2 Antibody

WANG, Zhiqing, Long LI, Janice G. PENNINGTON, Ju SHENG, Moh Lan YAP et. al.

Základní údaje

Originální název

Obstruction of Dengue Virus Maturation by Fab Fragments of the 2H2 Antibody

Autoři

WANG, Zhiqing, Long LI, Janice G. PENNINGTON, Ju SHENG, Moh Lan YAP, Pavel PLEVKA, Geng MENG, Lei SUN, Wen JIANG a Michael G. ROSSMANN

Vydání

JOURNAL OF VIROLOGY, WASHINGTON, AMER SOC MICROBIOLOGY, 2013, 0022-538X

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10600 1.6 Biological sciences

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 4.648

Organizační jednotka

Středoevropský technologický institut

DOI

http://dx.doi.org/10.1128/JVI.00472-13

UT WoS

000322535600009

Klíčová slova anglicky

INFECTION; PARTICLES; SUITE

Štítky

neMU

Změněno: 29. 3. 2017 11:12, Mgr. Eva Špillingová

Anotace

V originále

The 2H2 monoclonal antibody recognizes the precursor peptide on immature dengue virus and might therefore be a useful tool for investigating the conformational change that occurs when the immature virus enters an acidic environment. During dengue virus maturation, spiky, immature, noninfectious virions change their structure to form smooth-surfaced particles in the slightly acidic environment of the trans-Golgi network, thereby allowing cellular furin to cleave the precursor-membrane proteins. The dengue virions become fully infectious when they release the cleaved precursor peptide upon reaching the neutral-pH environment of the extracellular space. Here we report on the cryo-electron microscopy structures of the immature virus complexed with the 2H2 antigen binding fragments (Fab) at different concentrations and under various pH conditions. At neutral pH and a high concentration of Fab molecules, three Fab molecules bind to three precursor-membrane proteins on each spike of the immature virus. However, at a low concentration of Fab molecules and pH 7.0, only two Fab molecules bind to each spike. Changing to a slightly acidic pH caused no detectable change of structure for the sample with a high Fab concentration but caused severe structural damage to the low-concentration sample. Therefore, the 2H2 Fab inhibits the maturation process of immature dengue virus when Fab molecules are present at a high concentration, because the three Fab molecules on each spike hold the precursor-membrane molecules together, thereby inhibiting the normal conformational change that occurs during maturation.

Citovat

WANG, Zhiqing, Long LI, Janice G. PENNINGTON, Ju SHENG, Moh Lan YAP, Pavel PLEVKA, Geng MENG, Lei SUN, Wen JIANG a Michael G. ROSSMANN. Obstruction of Dengue Virus Maturation by Fab Fragments of the 2H2 Antibody. JOURNAL OF VIROLOGY. WASHINGTON: AMER SOC MICROBIOLOGY, 2013, roč. 87, č. 16, s. 8909-8915. ISSN 0022-538X. Dostupné z: https://dx.doi.org/10.1128/JVI.00472-13.

@article{1376795,
   author = {Wang, Zhiqing and Li, Long and Pennington, Janice G. and Sheng, Ju and Yap, Moh Lan and Plevka, Pavel and Meng, Geng and Sun, Lei and Jiang, Wen and Rossmann, Michael G.},
   article_location = {WASHINGTON},
   article_number = {16},
   doi = {http://dx.doi.org/10.1128/JVI.00472-13},
   keywords = {INFECTION; PARTICLES; SUITE},
   language = {eng},
   issn = {0022-538X},
   journal = {JOURNAL OF VIROLOGY},
   title = {Obstruction of Dengue Virus Maturation by Fab Fragments of the 2H2 Antibody},
   volume = {87},
   year = {2013}
}

TY  - JOUR
ID  - 1376795
AU  - Wang, Zhiqing - Li, Long - Pennington, Janice G. - Sheng, Ju - Yap, Moh Lan - Plevka, Pavel - Meng, Geng - Sun, Lei - Jiang, Wen - Rossmann, Michael G.
PY  - 2013
TI  - Obstruction of Dengue Virus Maturation by Fab Fragments of the 2H2 Antibody
JF  - JOURNAL OF VIROLOGY
VL  - 87
IS  - 16
SP  - 8909-8915
EP  - 8909-8915
PB  - AMER SOC MICROBIOLOGY
SN  - 0022538X
KW  - INFECTION
KW  - PARTICLES
KW  - SUITE
N2  - The 2H2 monoclonal antibody recognizes the precursor peptide on immature dengue virus and might therefore be a useful tool for investigating the conformational change that occurs when the immature virus enters an acidic environment. During dengue virus maturation, spiky, immature, noninfectious virions change their structure to form smooth-surfaced particles in the slightly acidic environment of the trans-Golgi network, thereby allowing cellular furin to cleave the precursor-membrane proteins. The dengue virions become fully infectious when they release the cleaved precursor peptide upon reaching the neutral-pH environment of the extracellular space. Here we report on the cryo-electron microscopy structures of the immature virus complexed with the 2H2 antigen binding fragments (Fab) at different concentrations and under various pH conditions. At neutral pH and a high concentration of Fab molecules, three Fab molecules bind to three precursor-membrane proteins on each spike of the immature virus. However, at a low concentration of Fab molecules and pH 7.0, only two Fab molecules bind to each spike. Changing to a slightly acidic pH caused no detectable change of structure for the sample with a high Fab concentration but caused severe structural damage to the low-concentration sample. Therefore, the 2H2 Fab inhibits the maturation process of immature dengue virus when Fab molecules are present at a high concentration, because the three Fab molecules on each spike hold the precursor-membrane molecules together, thereby inhibiting the normal conformational change that occurs during maturation.
ER  -

WANG, Zhiqing, Long LI, Janice G. PENNINGTON, Ju SHENG, Moh Lan YAP, Pavel PLEVKA, Geng MENG, Lei SUN, Wen JIANG a Michael G. ROSSMANN. Obstruction of Dengue Virus Maturation by Fab Fragments of the 2H2 Antibody. \textit{JOURNAL OF VIROLOGY}. WASHINGTON: AMER SOC MICROBIOLOGY, 2013, roč.~87, č.~16, s.~8909-8915. ISSN~0022-538X. Dostupné z: https://dx.doi.org/10.1128/JVI.00472-13.

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