scholarly journals Single Amino Acid Substitutions Surrounding the Icosahedral Fivefold Symmetry Axis Are Critical for Alternative Receptor Usage of Foot-and-Mouth Disease Virus

Viruses ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 1147
Author(s):  
Xiao-Hua Gong ◽  
Xing-Wen Bai ◽  
Ping-Hua Li ◽  
Hui-Fang Bao ◽  
Meng Zhang ◽  
...  
Keyword(s):  
Disease Virus ◽  
Symmetry Axis ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Single Amino Acid ◽  
Phenotypic Properties ◽  
Evolutionary Mechanisms ◽  
Fivefold Symmetry ◽  
Mouth Disease Virus ◽  
Foot And Mouth

The integrins function as the primary receptor molecules for the pathogenic infection of foot-and-mouth disease virus (FMDV) in vivo, while the acquisition of a high affinity for heparan sulfate (HS) of some FMDV variants could be privileged to facilitate viral infection and expanded cell tropism in vitro. Here, we noted that a BHK-adapted Cathay topotype derivative (O/HN/CHA/93tc) but not its genetically engineered virus (rHN), was able to infect HS-positive CHO-K1 cells and mutant pgsD-677 cells. There were one or three residue changes in the capsid proteins of O/HN/CHA/93tc and rHN, as compared with that of their tissue-originated isolate (O/HN/CHA/93wt). The phenotypic properties of a set of site-directed mutants of rHN revealed that E83K of VP1 surrounding the fivefold symmetry axis was necessary for the integrin-independent infection of O/HN/CHA/93tc. L80 in VP2 was essential for the occurrence of E83K in VP1 during the adaptation of O/HN/CHA/93wt to BHK-21 cells. L80M in VP2 and D138G in VP1 of rHN was deleterious, which could be compensated by K83R of VP1 for restoring an efficient infection of integrin-negative CHO cell lines. These might have important implications for understanding the molecular and evolutionary mechanisms of the recognition and binding of FMDV with alternative cellular receptors.

scholarly journals A Single Amino Acid Substitution in the Capsid of Foot-and-Mouth Disease Virus Can Increase Acid Lability and Confer Resistance to Acid-Dependent Uncoating Inhibition

2010 ◽  
Vol 84 (6) ◽  
pp. 2902-2912 ◽  
Author(s):  
Miguel A. Martín-Acebes ◽  
Verónica Rincón ◽  
Rosario Armas-Portela ◽  
Mauricio G. Mateu ◽  
Francisco Sobrino
Keyword(s):  
Amino Acid ◽  
Disease Virus ◽  
Amino Acid Substitution ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Single Amino Acid ◽  
Concanamycin A ◽  
Endosomal Acidification ◽  
Mouth Disease Virus ◽  
Foot And Mouth

ABSTRACT The acid-dependent disassembly of foot-and-mouth disease virus (FMDV) is required for viral RNA release from endosomes to initiate replication. Although the FMDV capsid disassembles at acid pH, mutants escaping inhibition by NH4Cl of endosomal acidification were found to constitute about 10% of the viruses recovered from BHK-21 cells infected with FMDV C-S8c1. For three of these mutants, the degree of NH4Cl resistance correlated with the sensitivity of the virion to acid-induced inactivation of its infectivity. Capsid sequencing revealed the presence in each of these mutants of a different amino acid substitution (VP3 A123T, VP3 A118V, and VP2 D106G) that affected a highly conserved residue among FMDVs located close to the capsid interpentameric interfaces. These residues may be involved in the modulation of the acid-induced dissociation of the FMDV capsid. The substitution VP3 A118V present in mutant c2 was sufficient to confer full resistance to NH4Cl and concanamycin A (a V-ATPase inhibitor that blocks endosomal acidification) as well as to increase the acid sensitivity of the virion to an extent similar to that exhibited by mutant c2 relative to the sensitivity of the parental virus C-S8c1. In addition, the increased propensity to dissociation into pentameric subunits of virions bearing substitution VP3 A118V indicates that this replacement also facilitates the dissociation of the FMDV capsid.

scholarly journals Sequence adaptations affecting cleavage of the VP1/2A junction by the 3C protease in foot-and-mouth disease virus-infected cells

2014 ◽  
Vol 95 (11) ◽  
pp. 2402-2410 ◽  
Author(s):  
Maria Gullberg ◽  
Charlotta Polacek ◽  
Graham J. Belsham
Keyword(s):  
Disease Virus ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Single Amino Acid ◽  
Virus Particles ◽  
3C Protease ◽  
Serotype O ◽  
Single Amino Acid Residue ◽  
Mouth Disease Virus ◽  
Foot And Mouth

The foot-and-mouth disease virus (FMDV) capsid protein precursor P1-2A is cleaved by the virus-encoded 3C protease to VP0, VP3, VP1 and 2A. It was shown previously that modification of a single amino acid residue (K210E) within the VP1 protein and close to the VP1/2A cleavage site, inhibited cleavage of this junction and produced ‘self-tagged’ virus particles. A second site substitution (E83K) within VP1 was also observed within the rescued virus [Gullberg et al. (2013). J Virol 87, 11591–11603]. It was shown here that introduction of this E83K change alone into a serotype O virus resulted in the rapid accumulation of a second site substitution within the 2A sequence (L2P), which also blocked VP1/2A cleavage. This suggests a linkage between the E83K change in VP1 and cleavage of the VP1/2A junction. Cells infected with viruses containing the VP1 K210E or the 2A L2P substitutions contained the uncleaved VP1-2A protein. The 2A L2P substitution resulted in the VP1/2A junction being highly resistant to cleavage by the 3C protease, hence it may be a preferred route for ‘tagging’ virus particles.

scholarly journals Targeted Modification of the Foot-And-Mouth Disease Virus Genome for Quick Cell Culture Adaptation

2020 ◽  
Author(s):  
Veronika Dill ◽  
Aline Zimmer ◽  
Martin Beer ◽  
Michael Eschbaumer
Keyword(s):  
Cell Line ◽  
Disease Virus ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Productive Infection ◽  
Single Amino Acid ◽  
Adaptive Mutations ◽  
Mouth Disease Virus ◽  
Foot And Mouth

Foot-and-mouth disease virus (FMDV) causes the highly contagious foot-and-mouth disease, which is characterized by the appearance of vesicles in and around the mouth and feet of cloven-hoofed animals. BHK21 cells are the cell line of choice for the propagation of FMDV for vaccine production world-wide but vary in their susceptibility for different FMDV strains. Previous studies showed that the FMDV resistance of a certain BHK cell line can be overcome by using a closely related but permissive cell line for the pre-adaptation of the virus, but the adapted strains were found to harbor several capsid mutations. In this study, these adaptive mutations were introduced into the original Asia-1 Shamir isolate individually or in combination to create a panel of 17 Asia-1 mutants by reverse genetics and examine the effects of the mutations on receptor usage, viral growth, immunogenicity and stability. A single amino acid exchange from glutamic acid to lysine at position 202 in VP1 turned out to be of major importance for productive infection of the suspension cell line BHK-2P. In consequence, two traditionally passage-derived strains and two recombinant viruses with a minimum set of mutations were tested in vivo. While the passaged-derived viruses showed a reduced particle stability, the genetically modified viruses were more stable but did not confer a protective immune response against the original virus isolate.

scholarly journals Targeted Modification of the Foot-And-Mouth Disease Virus Genome for Quick Cell Culture Adaptation

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 583
Author(s):  
Veronika Dill ◽  
Aline Zimmer ◽  
Martin Beer ◽  
Michael Eschbaumer
Keyword(s):  
Cell Line ◽  
Disease Virus ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Productive Infection ◽  
Single Amino Acid ◽  
Adaptive Mutations ◽  
Mouth Disease Virus ◽  
Foot And Mouth

Foot-and-mouth disease virus (FMDV) causes the highly contagious foot-and-mouth disease, which is characterized by the appearance of vesicles in and around the mouth and feet of cloven-hoofed animals. BHK-21 cells are the cell line of choice for the propagation of FMDV for vaccine production worldwide but vary in their susceptibility for different FMDV strains. Previous studies showed that the FMDV resistance of a certain BHK cell line can be overcome by using a closely related but permissive cell line for the pre-adaptation of the virus, but the adapted strains were found to harbor several capsid mutations. In this study, these adaptive mutations were introduced into the original Asia-1 Shamir isolate individually or in combination to create a panel of 17 Asia-1 mutants by reverse genetics and examine the effects of the mutations on receptor usage, viral growth, immunogenicity and stability. A single amino acid exchange from glutamic acid to lysine at position 202 in VP1 turned out to be of major importance for productive infection of the suspension cell line BHK-2P. In consequence, two traditionally passage-derived strains and two recombinant viruses with a minimum set of mutations were tested in vivo. While the passaged-derived viruses showed a reduced particle stability, the genetically modified viruses were more stable but did not confer a protective immune response against the original virus isolate.

scholarly journals Evidence of the Coevolution of Antigenicity and Host Cell Tropism of Foot-and-Mouth Disease Virus In Vivo

2003 ◽  
Vol 77 (2) ◽  
pp. 1219-1226 ◽  
Author(s):  
Cecilia Tami ◽  
Oscar Taboga ◽  
Analía Berinstein ◽  
José I. Núñez ◽  
Eduardo L. Palma ◽  
...  
Keyword(s):  
Amino Acid ◽  
Disease Virus ◽  
Significant Proportion ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Single Amino Acid ◽  
Cell Tropism ◽  
Mouth Disease Virus ◽  
Antigenic Properties ◽  
Foot And Mouth

ABSTRACT In this work we analyze the antigenic properties and the stability in cell culture of virus mutants recovered upon challenge of peptide-vaccinated cattle with foot-and-mouth disease virus (FMDV) C3 Arg85. Previously, we showed that a significant proportion of 29 lesions analyzed (41%) contained viruses with single amino acid replacements (R141G, L144P, or L147P) within a major antigenic site located at the G-H loop of VP1, known to participate also in interactions with integrin receptors. Here we document that no replacements at this site were found in viruses from 12 lesions developed in six control animals upon challenge with FMDV C3 Arg85. Sera from unprotected, vaccinated animals exhibited poor neutralization titers against mutants recovered from them. Sequence analyses of the viruses recovered upon 10 serial passages in BHK-21 and FBK-2 cells in the presence of preimmune (nonneutralizing) sera revealed that mutants reverted to the parental sequence, suggesting an effect of the amino acid replacements in the interaction of the viruses with cells. Parallel passages in the presence of subneutralizing concentrations of immune homologous sera resulted in the maintenance of mutations R141G and L147P, while mutation L144P reverted to the C3 Arg85 sequence. Reactivity with a panel of FMDV type C-specific monoclonal antibodies indicated that mutant viruses showed altered antigenicity. These results suggest that the selective pressure exerted by host humoral immune response can play a role in both the selection and stability of antigenic FMDV variants and that such variants can manifest alterations in cell tropism.

High resolution surface structure of foot-and-mouth disease virus

1978 ◽  
Vol 36 (2) ◽  
pp. 376-377
Author(s):  
S. S. Breese ◽  
H. L. Bachrach
Keyword(s):  
Electron Microscopy ◽  
High Resolution ◽  
Surface Structure ◽  
Disease Virus ◽  
Potassium Phosphate ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Physical Measurements ◽  
Mouth Disease Virus ◽  
Foot And Mouth

Models for the structure of foot-and-mouth disease virus (FMDV) have been proposed from chemical and physical measurements (Brown, et al., 1970; Talbot and Brown, 1972; Strohmaier and Adam, 1976) and from rotational image-enhancement electron microscopy (Breese, et al., 1965). In this report we examine the surface structure of FMDV particles by high resolution electron microscopy and compare it with that of particles in which the outermost capsid protein VP3 (ca. 30, 000 daltons) has been split into smaller segments, two of which VP3a and VP3b have molecular weights of about 15, 000 daltons (Bachrach, et al., 1975).Highly purified and concentrated type A12, strain 119 FMDV (5 mg/ml) was prepared as previously described (Bachrach, et al., 1964) and stored at 4°C in 0. 2 M KC1-0. 5 M potassium phosphate buffer at pH 7. 5. For electron microscopy, 1. 0 ml samples of purified virus and trypsin-treated virus were dialyzed at 4°C against 0. 2 M NH4OAC at pH 7. 3, deposited onto carbonized formvar-coated copper screens and stained with phosphotungstic acid, pH 7. 3.

Sign in / Sign up

Export Citation Format

Share Document