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.

Basic information

Original name

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

Authors

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

Edition

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

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10600 1.6 Biological sciences

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 4.648

Organization unit

Central European Institute of Technology

DOI

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

UT WoS

000322535600009

Keywords in English

INFECTION; PARTICLES; SUITE

Abstract

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 and Michael G. ROSSMANN. Obstruction of Dengue Virus Maturation by Fab Fragments of the 2H2 Antibody. JOURNAL OF VIROLOGY. WASHINGTON: AMER SOC MICROBIOLOGY, 2013, vol. 87, No 16, p. 8909-8915. ISSN 0022-538X. Available from: 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 and Michael G. ROSSMANN. Obstruction of Dengue Virus Maturation by Fab Fragments of the 2H2 Antibody. \textit{JOURNAL OF VIROLOGY}. WASHINGTON: AMER SOC MICROBIOLOGY, 2013, vol.~87, No~16, p.~8909-8915. ISSN~0022-538X. Available from: https://dx.doi.org/10.1128/JVI.00472-13.

Detailed Information on Publication Record