Immunogenicity of foot-and-mouth disease virus grown in BHK-21 suspensioncells. Correlation with cell ploidy alterations and abnormal expression of the α5β1 integrin

Amadori, Massimo; Berneri, C.; Archetti, I. L.

doi:10.1016/0264-410x(94)90055-8

Cited by 18 publications

(9 citation statements)

References 26 publications

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“…It has been previously suggested that the integrin ␣ 5 ␤ 1 might be a receptor for FMDV (2,25,85). K562 cells (17) and CHO-K1, pgsA-745, and pgsD-677 cells (not shown) express ␣ 5 ␤ 1 endogenously.…”

Section: Discussionmentioning

confidence: 89%

Foot-and-Mouth Disease Virus Virulent for Cattle Utilizes the Integrin α _v β ₃ as Its Receptor

Neff

Sá-Carvalho

Rieder

et al. 1998

J Virol

194

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Adsorption and plaque formation of foot-and-mouth disease virus (FMDV) serotype A12 are inhibited by antibodies to the integrin αvβ3 (A. Berinstein et al., J. Virol. 69:2664–2666, 1995). A human cell line, K562, which does not normally express αvβ3 cannot replicate this serotype unless cells are transfected with cDNAs encoding this integrin (K562-αvβ3 cells). In contrast, we found that a tissue culture-propagated FMDV, type O1BFS, was able to replicate in nontransfected K562 cells, and replication was not inhibited by antibodies to the endogenously expressed integrin α5β1. A recent report indicating that cell surface heparan sulfate (HS) was required for efficient infection of type O1 (T. Jackson et al., J. Virol. 70:5282–5287, 1996) led us to examine the role of HS and αvβ3 in FMDV infection. We transfected normal CHO cells, which express HS but not αvβ3, and two HS-deficient CHO cell lines with cDNAs encoding human αvβ3, producing a panel of cells that expressed one or both receptors. In these cells, type A12 replication was dependent on expression of αvβ3, whereas type O1BFS replicated to high titer in normal CHO cells but could not replicate in HS-deficient cells even when they expressed αvβ3. We have also analyzed two genetically engineered variants of type O1Campos, vCRM4, which has greatly reduced virulence in cattle and can bind to heparin-Sepharose columns, and vCRM8, which is highly virulent in cattle and cannot bind to heparin-Sepharose. vCRM4 replicated in wild-type K562 cells and normal, nontransfected CHO (HS+αvβ3− ) cells, whereas vCRM8 replicated only in K562 and CHO cells transfected with αvβ3 cDNAs. A similar result was also obtained in assays using a vCRM4 virus with an engineered RGD→KGE mutation. These results indicate that virulent FMDV utilizes the αvβ3 integrin as a primary receptor for infection and that adaptation of type O1 virus to cell culture results in the ability of the virus to utilize HS as a receptor and a concomitant loss of virulence.

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Section: Discussionmentioning

confidence: 89%

Foot-and-Mouth Disease Virus Virulent for Cattle Utilizes the Integrin α _v β ₃ as Its Receptor

Neff

Sá-Carvalho

Rieder

et al. 1998

J Virol

194

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“…Other characteristics that play a role in vaccine efficacy include the productivity and replication efficiency of the vaccine strain in the production cell line, a close antigenic relationship to field viruses circulating in current outbreaks, and the ability to provide protection against a wide range of antigenic variants in the field [2], [3]. However, adaptation of new vaccine strains in the production cell line (BHK-21) is difficult and hampered by low amounts of stable antigen, often rendering this method inefficient for commercial vaccine manufacturing purposes [4]–[6]. In addition, the hot climate in sub-Saharan Africa, where the South African Territories (SAT) types are prevalent, also calls for vaccines with improved stability which are less reliant on a cold chain during storage and handling.…”

Section: Introductionmentioning

confidence: 99%

Analysis of SAT Type Foot-And-Mouth Disease Virus Capsid Proteins and the Identification of Putative Amino Acid Residues Affecting Virus Stability

et al. 2013

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Foot-and-mouth disease virus (FMDV) initiates infection by adhering to integrin receptors on target cells, followed by cell entry and disassembly of the virion through acidification within endosomes. Mild heating of the virions also leads to irreversible dissociation into pentamers, a characteristic linked to reduced vaccine efficacy. In this study, the structural stability of intra- and inter-serotype chimeric SAT2 and SAT3 virus particles to various conditions including low pH, mild temperatures or high ionic strength, was compared. Our results demonstrated that while both the SAT2 and SAT3 infectious capsids displayed different sensitivities in a series of low pH buffers, their stability profiles were comparable at high temperatures or high ionic strength conditions. Recombinant vSAT2 and intra-serotype chimeric viruses were used to map the amino acid differences in the capsid proteins of viruses with disparate low pH stabilities. Four His residues at the inter-pentamer interface were identified that change protonation states at pH 6.0. Of these, the H145 of VP3 appears to be involved in interactions with A141 in VP3 and K63 in VP2, and may be involved in orientating H142 of VP3 for interaction at the inter-pentamer interfaces.

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“…Both vKNP/ SAT2 and KNP/196/91 displayed the cell culture-adaptation phenotype (Maree et al, 2010), possibly because of interactions with HSPG receptors (Jackson et al, 1996(Jackson et al, , 2003Sa-Carvalho et al, 1997;Fry et al, 1999). Such alteration in FMD viruses' ability to utilize HSPG is important as it is associated with more rapid replication in BHK-21 cells, a change in cell tropism, a more effective cell killing capacity and could contribute to improved production of FMD vaccines in suspension cultures (Amadori et al, 1994;Sevilla et al, 1996;Baranowski, et al, 1998). Vaccines were administered as a single inoculation at day 0.…”

Section: Discussionmentioning

confidence: 99%

Custom-engineered chimeric foot-and-mouth disease vaccine elicits protective immune responses in pigs

Blignaut

Visser²,

Theron

et al. 2010

Journal of General Virology

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Chimeric foot-and-mouth disease viruses (FMDV) of which the antigenic properties can be readily manipulated is a potentially powerful approach in the control of foot-and-mouth disease (FMD) in sub-Saharan Africa. FMD vaccine application is complicated by the extensive variability of the South African Territories (SAT) type viruses, which exist as distinct genetic and antigenic variants in different geographical regions. A cross-serotype chimeric virus, vKNP/SAT2, was engineered by replacing the external capsid-encoding region (1B-1D/2A) of an infectious cDNA clone of the SAT2 vaccine strain, ZIM/7/83, with that of SAT1 virus KNP/196/91. The vKNP/SAT2 virus exhibited comparable infection kinetics, virion stability and antigenic profiles to the KNP/196/91 parental virus, thus indicating that the functions provided by the capsid can be readily exchanged between serotypes. As these qualities are necessary for vaccine manufacturing, high titres of stable chimeric virus were obtained. Chemically inactivated vaccines, formulated as double-oil-in-water emulsions, were produced from intact 146S virion particles of both the chimeric and parental viruses. Inoculation of guinea pigs with the respective vaccines induced similar antibody responses. In order to show compliance with commercial vaccine requirements, the vaccines were evaluated in a full potency test. Pigs vaccinated with the chimeric vaccine produced neutralizing antibodies and showed protection against homologous FMDV challenge, albeit not to the same extent as for the vaccine prepared from the parental virus. These results provide support that chimeric vaccines containing the external capsid of field isolates can be successfully produced and that they induce protective immune responses in FMD host species.

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Immunogenicity of foot-and-mouth disease virus grown in BHK-21 suspensioncells. Correlation with cell ploidy alterations and abnormal expression of the α5β1 integrin

Cited by 18 publications

References 26 publications

Foot-and-Mouth Disease Virus Virulent for Cattle Utilizes the Integrin α _v β ₃ as Its Receptor

Foot-and-Mouth Disease Virus Virulent for Cattle Utilizes the Integrin α _v β ₃ as Its Receptor

Analysis of SAT Type Foot-And-Mouth Disease Virus Capsid Proteins and the Identification of Putative Amino Acid Residues Affecting Virus Stability

Custom-engineered chimeric foot-and-mouth disease vaccine elicits protective immune responses in pigs

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Immunogenicity of foot-and-mouth disease virus grown in BHK-21 suspensioncells. Correlation with cell ploidy alterations and abnormal expression of the α5β1 integrin

Cited by 18 publications

References 26 publications

Foot-and-Mouth Disease Virus Virulent for Cattle Utilizes the Integrin α v β 3 as Its Receptor

Foot-and-Mouth Disease Virus Virulent for Cattle Utilizes the Integrin α v β 3 as Its Receptor

Analysis of SAT Type Foot-And-Mouth Disease Virus Capsid Proteins and the Identification of Putative Amino Acid Residues Affecting Virus Stability

Custom-engineered chimeric foot-and-mouth disease vaccine elicits protective immune responses in pigs

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Product

Resources

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Foot-and-Mouth Disease Virus Virulent for Cattle Utilizes the Integrin α _v β ₃ as Its Receptor

Foot-and-Mouth Disease Virus Virulent for Cattle Utilizes the Integrin α _v β ₃ as Its Receptor