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 N- and 6-O-Sulfated Heparan Sulfates Mediate Internalization of Coxsackievirus B3 Variant PD into CHO-K1 Cells

2006 ◽  
Vol 80 (13) ◽  
pp. 6629-6636 ◽  
Author(s):  
Andreas E. Zautner ◽  
Birgit Jahn ◽  
Elke Hammerschmidt ◽  
Peter Wutzler ◽  
Michaela Schmidtke
Keyword(s):  
Growth Factor ◽  
Chinese Hamster Ovary ◽  
Chinese Hamster Ovary Cells ◽  
Chinese Hamster ◽  
Coxsackievirus B3 ◽  
Ovary Cells ◽  
Viral Binding ◽  
Heparan Sulfates ◽  
Time Required ◽  
Adenovirus Receptor

ABSTRACT Recently, it was demonstrated that the coxsackievirus B3 variant PD (CVB3 PD) is able to infect coxsackievirus-adenovirus receptor (CAR)-lacking cells by using heparan sulfates (HS) as additional receptors (A. E. Zautner, U. Korner, A. Henke, C. Badorff, and M. Schmidtke, J. Virol. 77:10071-10077, 2003). For this study, competition experiments with growth factors binding to known HS sequences as well as with specifically desulfated heparins were performed with Chinese hamster ovary cells (CHO-K1) to determine the structural requirements of HS for interaction with CVB3. Hepatocyte growth factor interacting with HS sequences containing [IdUA-GlcNSO3(6OSO3)] n , but not basic fibroblast growth factor binding to [HexUA-GlcNSO3-HexUA-GlcNSO3-IdUA(2OSO3)] n , was shown to compete effectively with CVB3 PD for cell surface HS. Whereas unmodified heparin and 2-O-desulfated heparin strongly inhibited the CVB3 PD-induced cytopathic effect, the antiviral activity was markedly reduced after N-, O- and 6-O-desulfation of heparin. Taken together, these results indicate that 6-O- and N-sulfation of GlcNAc of HS is crucial for HS interaction with CVB3 PD and that the disaccharide [IdUA-GlcNSO3(6OSO3)] n is involved in viral binding. Results from experiments with various inhibitors of endocytic pathways suggest that HS-mediated virus internalization is pH dependent. Despite the fact that CVB3 PD initiates infection about four times slower by making use of HS as a receptor than by using CAR, the time required for a complete viral life cycle in Chinese hamster ovary cells was independent of the utilized receptor.

scholarly journals Phylogenetic analysis of human rhinovirus capsid protein VP1 and 2A protease coding sequences confirms shared genus-like relationships with human enteroviruses

2005 ◽  
Vol 86 (3) ◽  
pp. 697-706 ◽  
Author(s):  
Pia Laine ◽  
Carita Savolainen ◽  
Soile Blomqvist ◽  
Tapani Hovi
Keyword(s):  
Phylogenetic Analysis ◽  
Amino Acid ◽  
Capsid Protein ◽  
Phylogenetic Trees ◽  
Amino Acid Sequences ◽  
Human Rhinovirus ◽  
Human Enterovirus ◽  
Coding Region ◽  
Coding Sequences ◽  
Capsid Protein Vp1

Phylogenetic analysis of the capsid protein VP1 coding sequences of all 101 human rhinovirus (HRV) prototype strains revealed two major genetic clusters, similar to that of the previously reported VP4/VP2 coding sequences, representing the established two species, Human rhinovirus A (HRV-A) and Human rhinovirus B (HRV-B). Pairwise nucleotide identities varied from 61 to 98 % within and from 46 to 55 % between the two HRV species. Interserotypic sequence identities in both HRV species were more variable than those within any Human enterovirus (HEV) species in the same family. This means that unequivocal serotype identification by VP1 sequence analysis used for HEV strains may not always be possible for HRV isolates. On the other hand, a comprehensive insight into the relationships between VP1 and partial 2A sequences of HRV and HEV revealed a genus-like situation. Distribution of pairwise nucleotide identity values between these genera varied from 41 to 54 % in the VP1 coding region, similar to those between heterologous members of the two HRV species. Alignment of the deduced amino acid sequences revealed more fully conserved amino acid residues between HRV-B and polioviruses than between the two HRV species. In phylogenetic trees, where all HRVs and representatives from all HEV species were included, the two HRV species did not cluster together but behaved like members of the same genus as the HEVs. In conclusion, from a phylogenetic point of view, there are no good reasons to keep these two human picornavirus genera taxonomically separated.

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 Population Genomics of GII.4 Noroviruses Reveal Complex Diversification and New Antigenic Sites Involved in the Emergence of Pandemic Strains

2019 ◽  
Author(s):  
Kentaro Tohma ◽  
Cara J. Lepore ◽  
Yamei Gao ◽  
Lauren A. Ford-Siltz ◽  
Gabriel I. Parra
Keyword(s):  
Amino Acid ◽  
Capsid Protein ◽  
Large Scale ◽  
Population Genomics ◽  
Viral Capsid ◽  
Viral Gastroenteritis ◽  
Viral Capsid Protein ◽  
Antigenic Sites ◽  
Capsid Protein Vp1

AbstractGII.4 noroviruses are a major cause of acute gastroenteritis. Their dominance has been partially explained by the continuous emergence of antigenically distinct variants. To gain insights on the mechanisms of viral emergence and population dynamics of GII.4 noroviruses, we performed large-scale genomics, structural, and mutational analyses of the viral capsid protein (VP1). GII.4 noroviruses exhibited a periodic replacement of predominant variants with accumulation of amino acid substitutions. Genomic analyses revealed (i) a large number (87%) of conserved residues; (ii) variable residues that map on the previously determined antigenic sites; and (iii) variable residues that map outside of the antigenic sites. Residues from the third pattern formed motifs on the surface of VP1, which suggested extensions of previously predicted and new uncharacterized antigenic sites. The role of two motifs (C and G) in the antigenic make-up of the GII.4 capsid protein was confirmed with monoclonal antibodies and carbohydrate blocking assays. Amino acid profiles from antigenic sites (A, C, D, E, and G) correlated with the circulation patterns of GII.4 variants, with two of them (C and G) containing residues (352, 357, 378) linked with the emergence of new GII.4 variants. Notably, the emergence of each variant was followed by a stochastic diversification with minimal changes at the antigenic sites that did not progress towards the next variant. This study provides a methodological framework for antigenic characterization of viruses, and expands our understanding of the dynamics of GII.4 noroviruses that could facilitate the design of cross-reactive vaccines.ImportanceNoroviruses are an important cause of viral gastroenteritis around the world. An obstacle delaying the development of norovirus vaccines is an inadequate understanding of the role of norovirus diversity in immunity. Using a population genomics approach, we identified new residues on the viral capsid protein (VP1) from GII.4 noroviruses, the predominant genotype, that appear to be involved in the emergence and antigenic topology of GII.4 variants. Careful monitoring of the substitutions in those residues involved in the diversification and emergence of new viruses could help in the early detection of future novel variants with pandemic potential. Therefore, this novel information on the antigenic diversification could facilitate GII.4 norovirus vaccine design.

Amino Acid Substitutions At Residue 207 of Viral Capsid Protein 1 (VP1) Confer Pleconaril Resistance in Coxsackievirus B3 (CVB3)

2011 ◽  
Vol 90 (2) ◽  
pp. A54-A55 ◽  
Author(s):  
Heike Braun ◽  
Vadim A. Makarov ◽  
Olga B. Riabova ◽  
Peter Wutzler ◽  
Michaela Schmidtke
Keyword(s):  
Amino Acid ◽  
Capsid Protein ◽  
Coxsackievirus B3 ◽  
Viral Capsid ◽  
Amino Acid Substitutions ◽  
Viral Capsid Protein

scholarly journals Population Genomics of GII.4 Noroviruses Reveal Complex Diversification and New Antigenic Sites Involved in the Emergence of Pandemic Strains

mBio ◽  
2019 ◽  
Vol 10 (5) ◽  
Author(s):  
Kentaro Tohma ◽  
Cara J. Lepore ◽  
Yamei Gao ◽  
Lauren A. Ford-Siltz ◽  
Gabriel I. Parra
Keyword(s):  
Amino Acid ◽  
Capsid Protein ◽  
Large Scale ◽  
Population Genomics ◽  
Viral Capsid ◽  
Viral Gastroenteritis ◽  
Viral Capsid Protein ◽  
Antigenic Sites ◽  
Capsid Protein Vp1

ABSTRACT GII.4 noroviruses are a major cause of acute gastroenteritis. Their dominance has been partially explained by the continuous emergence of antigenically distinct variants. To gain insights into the mechanisms of viral emergence and population dynamics of GII.4 noroviruses, we performed large-scale genomics, structural, and mutational analyses of the viral capsid protein (VP1). GII.4 noroviruses exhibited a periodic replacement of predominant variants with accumulation of amino acid substitutions. Genomic analyses revealed (i) a large proportion (87%) of conserved residues; (ii) variable residues that map on the previously determined antigenic sites; and (iii) variable residues that map outside the antigenic sites. Residues in the third pattern category formed motifs on the surface of VP1, which suggested extensions of previously predicted and new uncharacterized antigenic sites. The role of two motifs (C and G) in the antigenic makeup of the GII.4 capsid protein was confirmed with monoclonal antibodies and carbohydrate blocking assays. Amino acid profiles from antigenic sites (A, C, D, E, and G) correlated with the circulation patterns of GII.4 variants, with three of them (A, C, and G) containing residues (352, 357, 368, and 378) linked with the diversifying selective pressure on the emergence of new GII.4 variants. Notably, the emergence of each variant was followed by stochastic diversification with minimal changes that did not progress toward the next variant. This report provides a methodological framework for antigenic characterization of viruses and expands our understanding of the dynamics of GII.4 noroviruses and could facilitate the design of cross-reactive vaccines. IMPORTANCE Noroviruses are an important cause of viral gastroenteritis around the world. An obstacle delaying the development of norovirus vaccines is inadequate understanding of the role of norovirus diversity in immunity. Using a population genomics approach, we identified new residues on the viral capsid protein (VP1) from GII.4 noroviruses, the predominant genotype, that appear to be involved in the emergence and antigenic topology of GII.4 variants. Careful monitoring of the substitutions in those residues involved in the diversification and emergence of new viruses could help in the early detection of future novel variants with pandemic potential. Therefore, this novel information on the antigenic diversification could facilitate GII.4 norovirus vaccine design.

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