scholarly journals Attachment of Coxsackievirus B3 Variants to Various Cell Lines: Mapping of Phenotypic Differences to Capsid Protein VP1

Virology ◽  
2000 ◽  
Vol 275 (1) ◽  
pp. 77-88 ◽  
Author(s):  
M. Schmidtke ◽  
H.-C. Selinka ◽  
A. Heim ◽  
B. Jahn ◽  
M. Tonew ◽  
...  
Keyword(s):  
Capsid Protein ◽  
Cell Lines ◽  
Coxsackievirus B3 ◽  
Phenotypic Differences ◽  
Capsid Protein Vp1

scholarly journals Heparan Sulfates and Coxsackievirus-Adenovirus Receptor: Each One Mediates Coxsackievirus B3 PD Infection

2003 ◽  
Vol 77 (18) ◽  
pp. 10071-10077 ◽  
Author(s):  
A. E. Zautner ◽  
U. Körner ◽  
A. Henke ◽  
C. Badorff ◽  
M. Schmidtke
Keyword(s):  
Amino Acid ◽  
Capsid Protein ◽  
Critical Role ◽  
Chinese Hamster ◽  
Coxsackievirus B3 ◽  
Productive Infection ◽  
Human Hepatocyte Growth Factor ◽  
Heparan Sulfates ◽  
Capsid Protein Vp1 ◽  
Adenovirus Receptor

ABSTRACT Amino acid exchanges in the virus capsid protein VP1 allow the coxsackievirus B3 variant PD (CVB3 PD) to replicate in decay accelerating factor (DAF)-negative and coxsackievirus-adenovirus receptor (CAR)-negative cells. This suggests that molecules other than DAF and CAR are involved in attachment of this CVB3 variant to cell surfaces. The observation that productive infection associated with cytopathic effect occurred in Chinese hamster ovary (CHO-K1) cells, whereas heparinase-treated CHO-K1 cells, glucosaminoglycan-negative pgsA-745, heparan sulfate (HS)-negative pgsD-677, and pgsE-606 cells with significantly reduced N-sulfate expression resist CVB3 PD infection, indicates a critical role of highly sulfated HS. 2-O-sulfate-lacking pgsF-17 cells represented the cell line with minimum HS modifications susceptible for CVB3 PD. Inhibition of virus replication in CHO-K1 cells by polycationic compounds, pentosan polysulfate, lung heparin, and several intestinal but not kidney HS supported the hypothesis that CVB3 PD uses specific modified HS for entry. In addition, recombinant human hepatocyte growth factor blocked CVB3 PD infection. However, CAR also mediates CVB3 PD infection, because this CVB3 variant replicates in HS-lacking but CAR-bearing Raji cells, infection could be prevented by pretreatment of cells with CAR antibody, and HS-negative pgsD-677 cells transfected with CAR became susceptible for CVB3 PD. These results demonstrate that the amino acid substitutions in the viral capsid protein VP1 enable CVB3 PD to use specific modified HS as an entry receptor in addition to CAR.

scholarly journals A Genetically Engineered Attenuated Coxsackievirus B3 Strain Protects Mice against Lethal Infection

2005 ◽  
Vol 79 (14) ◽  
pp. 9285-9295 ◽  
Author(s):  
M. Dan ◽  
J. K. Chantler
Keyword(s):  
Glutamic Acid ◽  
Capsid Protein ◽  
Coxsackievirus B3 ◽  
Genetically Engineered ◽  
High Dose ◽  
Older Children ◽  
Triple Mutant ◽  
Lethal Challenge ◽  
Live Attenuated Vaccine ◽  
Capsid Protein Vp1

ABSTRACT Coxsackievirus B3 (CVB3) is a common human pathogen that is endemic throughout the world. There is currently no vaccine available, although the virus is known to be highly lethal to newborns and has been associated with heart disease and pancreatitis in older children and adults. Previously, we showed that the virulence of CVB3 is reduced by a lysine-to-arginine substitution in the capsid protein VP2 (K2168R) or a glutamic acid-to-glycine substitution in VP3 (E3060G). In this report, we show that the double mutant virus CVB3(KR/EG) displays additional attenuation, particularly for the pancreas, in A/J mice. In addition, two other attenuating mutations have been identified in the capsid protein VP1. When either the aspartic acid residue D1155 was replaced with glutamic acid or the proline residue P1126 was replaced with methionine, the resulting mutant also possessed an attenuated phenotype. Moreover, when either of these mutations was incorporated into CVB3(KR/EG), the resulting triple mutant viruses, CVB3(KR/EG/DE) and CVB3(KR/EG/PM), were completely noncardiovirulent and caused only small foci of damage to the pancreas, even at a high dose. Both triple mutants were found to be immunogenic, and a single injection of young A/J mice with either was found to protect them from a subsequent lethal challenge with wild-type CVB3. These findings indicate that the triple mutants could be exploited for the development of a live attenuated vaccine against CVB3.

Self-assembly of purified polyomavirus capsid protein VP1

Cell ◽  
1986 ◽  
Vol 46 (6) ◽  
pp. 895-904 ◽  
Author(s):  
Dinakar M. Salunke ◽  
Donald L.D. Caspar ◽  
Robert L. Garcea
Keyword(s):  
Capsid Protein ◽  
Self Assembly ◽  
Capsid Protein Vp1

scholarly journals Genetic Analysis of the Major Capsid Protein of the Archaeal Fusellovirus SSV1: Mutational Flexibility and Conformational Change

2017 ◽  
Author(s):  
Eric A. Iverson ◽  
David A. Goodman ◽  
Madeline E. Gorchels ◽  
Kenneth M. Stedman
Keyword(s):  
Capsid Protein ◽  
Major Capsid Protein ◽  
Point Mutations ◽  
Site Directed Mutagenesis ◽  
Vp1 Gene ◽  
Capsid Protein Gene ◽  
Vp1 Protein ◽  
Transposon Insertion ◽  
N Terminus ◽  
Capsid Protein Vp1

Viruses with spindle or lemon-shaped virions are rare in the world of viruses, but are common in viruses of archaeal extremophiles, possibly due to the extreme conditions in which they thrive. However, the structural and genetic basis for the unique spindle shape is unknown. The best-studied spindle-shaped virus, SSV1, is composed mostly of the major capsid protein VP1. Similar to many other viruses, proteolytic cleavage of VP1 is thought to be critical for virion formation. Unlike half of the genes in SSV1, including the minor capsid protein gene vp3, the vp1 gene does not tolerate deletion or transposon insertion. In order determine the role of the vp1 gene and its proteolysis for virus function, we developed techniques for site-directed mutagenesis of the SSV1 genome and complemented deletion mutants with vp1 genes from other SSVs. By analyzing these mutants we demonstrate that the N-terminus of the VP1 protein is required, but the N-terminus, or entire SSV1 VP1 protein, can be exchanged with VP1s from other SSVs. However, the conserved glutamate at the cleavage site is not essential for infectivity. Interestingly, viruses containing point mutations at this position generate mostly abnormal virions.

scholarly journals Genetic Analysis of the Major Capsid Protein of the Archaeal Fusellovirus SSV1: Mutational Flexibility and Conformational Change

2017 ◽  
Author(s):  
Eric A. Iverson ◽  
David A. Goodman ◽  
Madeline E. Gorchels ◽  
Kenneth M. STEDMAN
Keyword(s):  
Capsid Protein ◽  
Major Capsid Protein ◽  
Point Mutations ◽  
Site Directed Mutagenesis ◽  
Vp1 Gene ◽  
Vp1 Protein ◽  
Transposon Insertion ◽  
N Terminus ◽  
Capsid Protein Vp1 ◽  
Virion Formation

Viruses with spindle or lemon-shaped virions are rare in the world of viruses, but are common in viruses of archaeal extremophiles, possibly due to the extreme conditions in which they thrive. However, the structural and genetic basis for the unique spindle shape is unknown. The best-studied spindle-shaped virus, SSV1, is composed mostly of the major capsid protein VP1. Similar to many other viruses, proteolytic cleavage of VP1 is thought to be critical for virion formation. Unlike half of the genes in SSV1, including the minor capsid protein VP3, the vp1 gene does not tolerate deletion or transposon insertion. In order determine the role of the vp1 gene and its proteolysis for virus function, we developed techniques for site-directed mutagenesis of the SSV1 genome and complemented deletion mutants with vp1 genes from other SSVs. By analyzing these mutants we demonstrate that the N-terminus of the VP1 protein is required, but the N-terminus, or entire SSV1 VP1 protein, can be exchanged with VP1s from other SSVs. However, the conserved glutamate at the cleavage site is not essential. Interestingly, viruses containing point mutations at this position generate mostly abnormal virions.

scholarly journals Calicivirus VP2 forms a portal to mediate endosome escape

2018 ◽  
Author(s):  
Michaela Conley ◽  
Marion McElwee ◽  
Liyana Azmi ◽  
Mads Gabrielsen ◽  
Olwyn Byron ◽  
...  
Keyword(s):  
Capsid Protein ◽  
Conformational Changes ◽  
Structural Changes ◽  
Host Cells ◽  
Major Step ◽  
Endosomal Membrane ◽  
Endosome Escape ◽  
Animal Pathogens ◽  
Capsid Shell ◽  
Capsid Protein Vp1

AbstractTo initiate the infectious process, many viruses enter their host cells by triggering endocytosis following receptor engagement. The mechanism by which non-enveloped viruses, such as the caliciviruses, escape the endosome is however poorly understood. TheCaliciviridaeinclude many important human and animal pathogens, most notably norovirus, the cause of winter vomiting disease. Here we show that VP2, a minor capsid protein encoded by all caliciviruses, forms a large portal assembly at a unique three-fold symmetry axis following receptor engagement. This feature surrounds an open pore in the capsid shell. We hypothesise that the VP2 portal complex is the means by which the virus escapes the endosome, pene-trating the endosomal membrane to release the viral genome into the cytoplasm. Cryogenic electron microscopy (cryoEM) and asymmetric reconstruction were used to investigate structural changes in the capsid of feline calicivirus (FCV) that occur when the virus binds to its cellular receptor junctional adhesion molecule-A (fJAM-A). Near atomic-resolution structures were calculated for the native virion alone and decorated with soluble receptor fragments. We present atomic models of the major capsid protein VP1 in the presence and absence of fJAM-A, revealing the contact interface and conformational changes brought about by the interaction. Furthermore, we have calculated an atomic model of the portal protein VP2 and revealed the structural changes in VP1 that lead to pore formation. While VP2 was known to be critical for the production of infectious virus, its function has been hitherto undetermined. Our finding that VP2 assembles a portal that is likely responsible for endosome escape represents a major step forward in our understanding of both theCaliciviridaeand icosahedral RNA containing viruses in general.

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