scholarly journals Evaluation of Genetically Engineered Derivatives of a Chinese Strain of Foot-and-Mouth Disease Virus Reveals a Novel Cell-Binding Site Which Functions in Cell Culture and in Animals

2003 ◽  
Vol 77 (5) ◽  
pp. 3269-3280 ◽  
Author(s):  
Qizu Zhao ◽  
Juan M. Pacheco ◽  
Peter W. Mason
Keyword(s):  
Cell Culture ◽  
Cell Surface ◽  
Host Range ◽  
Disease Virus ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Cell Binding ◽  
Coding Regions ◽  
Mouth Disease Virus ◽  
Foot And Mouth

ABSTRACT Adaptation of field isolates of foot-and-mouth disease virus (FMDV) to grow in cells in culture can result in changes in viral properties that include acquisition of the ability to bind to cell surface heparan sulfate (HS). After 13 passages on BHK cells to produce a vaccine, a Cathay topotype isolate of FMDV serotype O from China (O/CHA/90) extended its cell culture host range and bound to heparin-Sepharose, although it did not require cell surface HS as a receptor molecule. To understand these phenomena, we constructed chimeric viruses by using a type A12 infectious cDNA and the capsid protein-coding regions of O/CHA/90 and its cell culture-adapted derivative (vac-O/CHA/90). Using a set of viruses derived from these chimeras by exchanging portions of the capsid-coding regions, we discovered that a group of amino acid residues that surround the fivefold axis of the icosahedral virion determine host range in cell culture and influence pathogenicity in pigs. These residues included aromatic amino acids at positions 108 and 174 and positively charged residues at positions 83 and 172 in protein 1D. To test if these residues participated in non-integrin-dependent cell binding, the integrin-binding RGD sequence in protein 1D was changed to KGE in two different chimeras. Evaluation of these KGE viruses indicated that growth in cell culture was not dependent on HS. One of these viruses was tested in pigs, where it produced a mild disease and maintained its KGE sequence. These results are discussed in terms of receptor utilization and pathogenesis of this important pathogen.

scholarly journals Sequence and phylogenetic analysis of the non-structural 3A and 3B protein-coding regions of foot-and-mouth disease virus subtype A Iran 05

2010 ◽  
Vol 11 (3) ◽  
pp. 243
Author(s):  
Saber Jelokhani-Niaraki ◽  
Majid Esmaelizad ◽  
Morteza Daliri ◽  
Rasoul Vaez-Torshizi ◽  
Morteza Kamalzadeh ◽  
...  
Keyword(s):  
Phylogenetic Analysis ◽  
Disease Virus ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Protein Coding ◽  
Coding Regions ◽  
Mouth Disease Virus ◽  
Foot And Mouth ◽  
Subtype A ◽  
Virus Subtype

scholarly journals Domain disruptions of individual 3B proteins of foot-and-mouth disease virus do not alter growth in cell culture or virulence in cattle

Virology ◽  
2010 ◽  
Vol 405 (1) ◽  
pp. 149-156 ◽  
Author(s):  
Juan M. Pacheco ◽  
Maria E. Piccone ◽  
Elizabeth Rieder ◽  
Steven J. Pauszek ◽  
Manuel V. Borca ◽  
...  
Keyword(s):  
Cell Culture ◽  
Disease Virus ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Mouth Disease Virus ◽  
Foot And Mouth

Sequence analysis of the protein-coding regions of foot-and-mouth disease virus O/HK/2001

2008 ◽  
Vol 130 (3-4) ◽  
pp. 238-246 ◽  
Author(s):  
Zhao Mingqiu ◽  
Suo Qingli ◽  
Chen Jinding ◽  
Chen Lijun ◽  
Xu Yanfang
Keyword(s):  
Sequence Analysis ◽  
Disease Virus ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Protein Coding ◽  
Coding Regions ◽  
Mouth Disease Virus ◽  
Foot And Mouth

scholarly journals Heparan Sulfate-Binding Foot-and-Mouth Disease Virus Enters Cells via Caveola-Mediated Endocytosis

2008 ◽  
Vol 82 (18) ◽  
pp. 9075-9085 ◽  
Author(s):  
Vivian O'Donnell ◽  
Michael LaRocco ◽  
Barry Baxt
Keyword(s):  
Cell Surface ◽  
Heparan Sulfate ◽  
Disease Virus ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Caveolin 1 ◽  
Viral Virulence ◽  
Fmdv Serotypes ◽  
Mouth Disease Virus ◽  
Foot And Mouth

ABSTRACT Foot-and-mouth disease virus (FMDV) utilizes different cell surface macromolecules to facilitate infection of cultured cells. Virus, which is virulent for susceptible animals, infects cells via four members of the αV subclass of cellular integrins. In contrast, tissue culture adaptation of some FMDV serotypes results in the loss of viral virulence in the animal, accompanied by the loss of virus' ability to use integrins as receptors. These avirulent viral variants acquire positively charged amino acids on surface-exposed structural proteins, resulting in the utilization of cell surface heparan sulfate (HS) molecules as receptors. We have recently shown that FMDV serotypes utilizing integrin receptors enter cells via a clathrin-mediated mechanism into early endosomes. Acidification within the endosome results in a breakdown of the viral capsid, releasing the RNA, which enters the cytoplasm by a still undefined mechanism. Since there is evidence that HS internalizes bound ligands via a caveola-mediated mechanism, it was of interest to analyze the entry of FMDV by cell-surface HS. Using a genetically engineered variant of type O1Campos (O1C3056R) which can utilize both integrins and HS as receptors and a second variant (O1C3056R-KGE) which can utilize only HS as a receptor, we followed viral entry using confocal microscopy. After virus bound to cells at 4°C, followed by a temperature shift to 37°C, type O1C3056R-KGE colocalized with caveolin-1, while O1C3056R colocalized with both clathrin and caveolin-1. Compounds which either disrupt or inhibit the formation of lipid rafts inhibited the replication of O1C3056R-KGE. Furthermore, a caveolin-1 knockdown by RNA interference also considerably reduced the efficiency of O1C3056R-KGE infection. These results indicate that HS-binding FMDV enters the cells via the caveola-mediated endocytosis pathway and that caveolae can associate and traffic with endosomes. In addition, these results further suggest that the route of FMDV entry into cells is a function solely of the viral receptor.

Simultaneous and staggered foot-and-mouth disease virus coinfection of cattle

2021 ◽  
Author(s):  
Jonathan Arzt ◽  
Ian H. Fish ◽  
Miranda R. Bertram ◽  
George R. Smoliga ◽  
Ethan J. Hartwig ◽  
...  
Keyword(s):  
Disease Virus ◽  
Foot And Mouth Disease ◽  
Field Studies ◽  
Mouth Disease ◽  
Coding Regions ◽  
Mouth Disease Virus ◽  
Foot And Mouth ◽  
Heterologous Virus ◽  
Virus Exposure ◽  
Upper Respiratory

Foot-and-mouth disease (FMD) field studies have suggested the occurrence of simultaneous infection of individual hosts by multiple virus strains; however, the pathogenesis of foot-and-mouth disease virus (FMDV) coinfections is largely unknown. In the current study, cattle were experimentally exposed to two FMDV strains of different serotypes (O and A). One cohort was simultaneously infected with both viruses, while additional cohorts were initially infected with FMDV A and subsequently superinfected with FMDV O, after 21 or 35 days. Coinfections were confirmed during acute infection, with both viruses concurrently detected in blood, lesions, and secretions. Staggered exposures resulted in overlapping infections as convalescent animals with persistent subclinical FMDV infection were superinfected with a heterologous virus. Staggering virus exposure by 21 days conferred clinical protection in six of eight cattle, which were subclinically infected following the heterologous virus exposure. This effect was transient, as all animals superinfected at 35 days post initial infection developed fulminant FMD. The majority of cattle maintained persistent infection with one of the two viruses while clearing the other. Analysis of viral genomes confirmed inter-serotypic recombination events within 10 days in the upper respiratory tract of five superinfected animals from which the dominant genomes contained the capsid coding regions of the O virus, and non-structural coding regions of the A virus. By contrast, there were no dominant recombinant genomes detected in samples from simultaneously coinfected cattle. These findings inculpate persistently infected carriers as potential FMDV mixing vessels in which novel strains may rapidly emerge through superinfection and recombination. Importance Foot-and-mouth disease (FMD) is a viral infection of livestock of critical socioeconomic importance. Field studies from areas of endemic FMD suggest that animals can be simultaneously infected by more than one distinct variant of FMD virus (FMDV), potentially resulting in emergence of novel viral strains through recombination. However, there has been limited investigation of the mechanisms of in vivo FMDV coinfections under controlled experimental conditions. Our findings confirmed that cattle could be simultaneously infected by two distinct serotypes of FMDV, with different outcomes associated with the timing of exposure to the two different viruses. Additionally, dominant inter-serotypic recombinant FMDVs were discovered in multiple samples from the upper respiratory tracts of five superinfected animals, emphasizing the potential importance of persistently infected FMDV carriers as sources of novel FMDV strains.

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