Skip to main content
Top
Published in: Virology Journal 1/2011

Open Access 01-12-2011 | Research

Establishment of persistent infection with foot-and-mouth disease virus in BHK-21 cells

Authors: Xuan Huang, Yong Li, Hui Fang, Congyi Zheng

Published in: Virology Journal | Issue 1/2011

Login to get access

Abstract

Background

Foot-and-mouth disease virus (FMDV) is able to cause persistent infection in ruminants besides acute infection and disease. Since the mechanisms of viral persistence and the determining factors are still unknown, in vitro systems help explore and reveal mechanisms of persistence in vivo by providing useful models for the study of RNA genome mutations and evolution. Ammonium chloride, a lysosomotropic agent that raises intralysosomal pH, reduces the yield of FMDV during infection of BHK-21 cells.

Results

The persistent infection with FMDV serotype O in BHK-21 cells was selected and established readily after treatment of ammonium chloride that acts primarily on the cells. Intact virions were observed located inside the endosomes. Viral genome RNAs and specific proteins were detected in the persistent cells to validate the establishment of viral persistence. Infection of the persistent viruses could not form plaques in host cells but virulence was enhanced. Basing on analysis and comparison of cDNA sequences of resident viruses and wild type viruses, 15 amine acid mutations were found, all of which were located in nonstructural proteins rather than in structural proteins.

Conclusions

Therefore, persistent infection of cell cultures with FMDV is successfully established with some distinctive features. It would be worthwhile to further investigate the mechanisms of viral persistence.
Appendix
Available only for authorised users
Literature
1.
go back to reference Lyles DS: Cytopathogenesis and inhibition of host gene expression by RNA viruses. Microbiol Mol Biol R. 2000, 64: 709-724. 10.1128/MMBR.64.4.709-724.2000.CrossRef Lyles DS: Cytopathogenesis and inhibition of host gene expression by RNA viruses. Microbiol Mol Biol R. 2000, 64: 709-724. 10.1128/MMBR.64.4.709-724.2000.CrossRef
2.
go back to reference Ron D, Tal J: Coevolution of cells and virus as a mechanism for the persistence of lymphotropic minute virus of mice in L-cells. J Virol. 1985, 55: 424-430.PubMedCentralPubMed Ron D, Tal J: Coevolution of cells and virus as a mechanism for the persistence of lymphotropic minute virus of mice in L-cells. J Virol. 1985, 55: 424-430.PubMedCentralPubMed
3.
go back to reference de la Torre JC, Martínez-salas E, Diez J, Villaverde A, Gebauer F, Rocha E, Dávila M, Domingo E: Coevolution of cells and viruses in a persistent infection of foot-and-mouth disease virus in cell culture. J Virol. 1988, 62: 2050-2058.PubMedCentralPubMed de la Torre JC, Martínez-salas E, Diez J, Villaverde A, Gebauer F, Rocha E, Dávila M, Domingo E: Coevolution of cells and viruses in a persistent infection of foot-and-mouth disease virus in cell culture. J Virol. 1988, 62: 2050-2058.PubMedCentralPubMed
4.
go back to reference Zárate S, Novella IS: Vesicular stomatitis virus evolution during alternation between persistent infection in insect cells and acute infection in mammalian cells in dominated by the persistence phase. J Virol. 2004, 78: 12236-12242.PubMedCentralCrossRefPubMed Zárate S, Novella IS: Vesicular stomatitis virus evolution during alternation between persistent infection in insect cells and acute infection in mammalian cells in dominated by the persistence phase. J Virol. 2004, 78: 12236-12242.PubMedCentralCrossRefPubMed
5.
go back to reference Zhang J, Timoney PJ, MacLachlan J, McCollum WH, Balasuriya UBR: Persistent equine arteritis virus infection in HeLa cells. J Virol. 2008, 82: 8456-8464. 10.1128/JVI.01249-08.PubMedCentralCrossRefPubMed Zhang J, Timoney PJ, MacLachlan J, McCollum WH, Balasuriya UBR: Persistent equine arteritis virus infection in HeLa cells. J Virol. 2008, 82: 8456-8464. 10.1128/JVI.01249-08.PubMedCentralCrossRefPubMed
6.
go back to reference Belsham GJ: Distinctive features of foot-and-mouth disease virus, a member of the picornavirus family: aspects of virus protein synthesis, protein processing and structure. Prog Biophys Mol Bio. 1993, 60: 241-260. 10.1016/0079-6107(93)90016-D.CrossRef Belsham GJ: Distinctive features of foot-and-mouth disease virus, a member of the picornavirus family: aspects of virus protein synthesis, protein processing and structure. Prog Biophys Mol Bio. 1993, 60: 241-260. 10.1016/0079-6107(93)90016-D.CrossRef
7.
go back to reference van Bekkum JG, Frenkel HS, Frederiks HHJ, Frenkel S: Observations on the carrier state of cattle exposed to foot and mouth disease virus. Tijdschr Diergeneeskd. 1959, 84: 1159-1164. van Bekkum JG, Frenkel HS, Frederiks HHJ, Frenkel S: Observations on the carrier state of cattle exposed to foot and mouth disease virus. Tijdschr Diergeneeskd. 1959, 84: 1159-1164.
8.
go back to reference Bachrach HL: Foot-and-mouth disease. Annu Rev Microbiol. 1968, 22: 201-244. 10.1146/annurev.mi.22.100168.001221.CrossRefPubMed Bachrach HL: Foot-and-mouth disease. Annu Rev Microbiol. 1968, 22: 201-244. 10.1146/annurev.mi.22.100168.001221.CrossRefPubMed
9.
go back to reference Mason PW, Grubman MJ, Baxt B: Molecular basis of pathogenesis of FMDV. Virus Res. 2003, 91: 9-32. 10.1016/S0168-1702(02)00257-5.CrossRefPubMed Mason PW, Grubman MJ, Baxt B: Molecular basis of pathogenesis of FMDV. Virus Res. 2003, 91: 9-32. 10.1016/S0168-1702(02)00257-5.CrossRefPubMed
11.
go back to reference Gromeier M, Wimmer E, Gorbalenya AE, Domingo E, Webster RG, Holland JJS: Origin and evolution of viruses. 1999, San Diego: Academic Press, 287-343.CrossRef Gromeier M, Wimmer E, Gorbalenya AE, Domingo E, Webster RG, Holland JJS: Origin and evolution of viruses. 1999, San Diego: Academic Press, 287-343.CrossRef
12.
go back to reference Mateo R, Mateu MG: Deterministic, compensatory mutational events in the capsid of foot-and-mouth disease virus in response to the introduction of mutations found in viruses from persistent infections. J Virol. 2007, 81: 1879-1887. 10.1128/JVI.01899-06.PubMedCentralCrossRefPubMed Mateo R, Mateu MG: Deterministic, compensatory mutational events in the capsid of foot-and-mouth disease virus in response to the introduction of mutations found in viruses from persistent infections. J Virol. 2007, 81: 1879-1887. 10.1128/JVI.01899-06.PubMedCentralCrossRefPubMed
13.
go back to reference Curry S, Abrams CC, Fry E, Crowther JC, Belsham GJ, Stuart DI, King AM: Viral RNA modulates the acid sensitivity of foot-and-mouth disease virus capsids. J Virol. 1995, 69: 430-438.PubMedCentralPubMed Curry S, Abrams CC, Fry E, Crowther JC, Belsham GJ, Stuart DI, King AM: Viral RNA modulates the acid sensitivity of foot-and-mouth disease virus capsids. J Virol. 1995, 69: 430-438.PubMedCentralPubMed
14.
go back to reference Johns HL, Berryman S, Monaghan P, Belsham GJ, Jackson T: A dominant-negative mutant of rab5 inhibits infection of cells by foot-and-mouth disease virus: implications for virus entry. J Virol. 2009, 83: 6247-6256. 10.1128/JVI.02460-08.PubMedCentralCrossRefPubMed Johns HL, Berryman S, Monaghan P, Belsham GJ, Jackson T: A dominant-negative mutant of rab5 inhibits infection of cells by foot-and-mouth disease virus: implications for virus entry. J Virol. 2009, 83: 6247-6256. 10.1128/JVI.02460-08.PubMedCentralCrossRefPubMed
15.
go back to reference Carrillo EC, Giachetti C, Campos RH: Effect of lysosomotropic agents on the foot-and-mouth disease virus replication. Virology. 1984, 135: 542-545. 10.1016/0042-6822(84)90208-3.CrossRefPubMed Carrillo EC, Giachetti C, Campos RH: Effect of lysosomotropic agents on the foot-and-mouth disease virus replication. Virology. 1984, 135: 542-545. 10.1016/0042-6822(84)90208-3.CrossRefPubMed
16.
go back to reference Baxt B: Effect of lysosomotropic compounds on early events in foot-and-mouth disease virus replication. Virus Res. 1987, 7: 257-271. 10.1016/0168-1702(87)90032-3.CrossRefPubMed Baxt B: Effect of lysosomotropic compounds on early events in foot-and-mouth disease virus replication. Virus Res. 1987, 7: 257-271. 10.1016/0168-1702(87)90032-3.CrossRefPubMed
17.
go back to reference Neubauer C, Frasel L, Kuechler E, Blaas D: Mechanism of entry of human rhinovirus 2 into HeLa cells. Virology. 1987, 158: 255-258. 10.1016/0042-6822(87)90264-9.CrossRefPubMed Neubauer C, Frasel L, Kuechler E, Blaas D: Mechanism of entry of human rhinovirus 2 into HeLa cells. Virology. 1987, 158: 255-258. 10.1016/0042-6822(87)90264-9.CrossRefPubMed
18.
go back to reference Martín-Acebes MA, Rincón V, Armas-Portela R, Mateu MG, Sobrino F: 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. J Virol. 2010, 84: 2902-2912.PubMedCentralCrossRefPubMed Martín-Acebes MA, Rincón V, Armas-Portela R, Mateu MG, Sobrino F: 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. J Virol. 2010, 84: 2902-2912.PubMedCentralCrossRefPubMed
19.
go back to reference Carrillo EC, Giachetti C, Campos RH: Early steps in FMDV replication: further analysis on the effects of chloroquine. Virology. 1985, 147: 118-125. 10.1016/0042-6822(85)90232-6.CrossRefPubMed Carrillo EC, Giachetti C, Campos RH: Early steps in FMDV replication: further analysis on the effects of chloroquine. Virology. 1985, 147: 118-125. 10.1016/0042-6822(85)90232-6.CrossRefPubMed
20.
go back to reference Dermody TS, Nibert ML, Wetzel JD, Tong X, Fields BN: Cells and viruses with mutations affecting viral entry are selected during persistent infections of L cells with mammalian reoviruses. J Virol. 1993, 67: 2055-2063.PubMedCentralPubMed Dermody TS, Nibert ML, Wetzel JD, Tong X, Fields BN: Cells and viruses with mutations affecting viral entry are selected during persistent infections of L cells with mammalian reoviruses. J Virol. 1993, 67: 2055-2063.PubMedCentralPubMed
21.
go back to reference Wetzel JD, Wilson GJ, Baer GS, Dunnigan LR, Wright JP, Tang DSH, Dermody TS: Reovirus variants selected during persistent infections of L cells contain mutations in the viral S1 and S4 genes and are altered in viral disassembly. J Virol. 1997, 71: 1362-1369.PubMedCentralPubMed Wetzel JD, Wilson GJ, Baer GS, Dunnigan LR, Wright JP, Tang DSH, Dermody TS: Reovirus variants selected during persistent infections of L cells contain mutations in the viral S1 and S4 genes and are altered in viral disassembly. J Virol. 1997, 71: 1362-1369.PubMedCentralPubMed
22.
go back to reference Liebl D, Difato F, Horníková L, Mannová P, Štokrová J, Forstová J: Mouse polyomavirus enters early endosomes, requires their acidic pH for productive infection, and meets transferrin cargo in Rab11-positive endosomes. J Virol. 2006, 80: 4610-4622. 10.1128/JVI.80.9.4610-4622.2006.PubMedCentralCrossRefPubMed Liebl D, Difato F, Horníková L, Mannová P, Štokrová J, Forstová J: Mouse polyomavirus enters early endosomes, requires their acidic pH for productive infection, and meets transferrin cargo in Rab11-positive endosomes. J Virol. 2006, 80: 4610-4622. 10.1128/JVI.80.9.4610-4622.2006.PubMedCentralCrossRefPubMed
23.
go back to reference Dabydeen SA, Meneses PI: The role of NH4Cl and cysteine proteases in Human Papillomavirus type 16 infection. Virol J. 2009, 6: 109-10.1186/1743-422X-6-109.PubMedCentralCrossRefPubMed Dabydeen SA, Meneses PI: The role of NH4Cl and cysteine proteases in Human Papillomavirus type 16 infection. Virol J. 2009, 6: 109-10.1186/1743-422X-6-109.PubMedCentralCrossRefPubMed
24.
go back to reference Canning WM, Fields BN: Ammonium chloride prevents lytic growth of reovirus and helps to establish persistent infection in mouse L cells. Science. 1983, 219: 987-988. 10.1126/science.6297010.CrossRefPubMed Canning WM, Fields BN: Ammonium chloride prevents lytic growth of reovirus and helps to establish persistent infection in mouse L cells. Science. 1983, 219: 987-988. 10.1126/science.6297010.CrossRefPubMed
25.
go back to reference de la Torre JC, Dávila M, Sobrino F, Ortin J, Domingo E: Establishment of cell lines persistently infected with foot-and-mouth disease virus. Virology. 1985, 145: 24-35. 10.1016/0042-6822(85)90198-9.CrossRefPubMed de la Torre JC, Dávila M, Sobrino F, Ortin J, Domingo E: Establishment of cell lines persistently infected with foot-and-mouth disease virus. Virology. 1985, 145: 24-35. 10.1016/0042-6822(85)90198-9.CrossRefPubMed
26.
go back to reference Martín Hernández AM, Carrillo EC, Sevilla N, Domingo E: Rapid cell variation can determine the establishment of a persistent viral infection. Proc Natl Acad Sci USA. 1994, 91: 3705-3709.PubMedCentralCrossRefPubMed Martín Hernández AM, Carrillo EC, Sevilla N, Domingo E: Rapid cell variation can determine the establishment of a persistent viral infection. Proc Natl Acad Sci USA. 1994, 91: 3705-3709.PubMedCentralCrossRefPubMed
27.
go back to reference Huang X, Li Y, Zheng C: A novel single-cell quantitative real-time RT-PCR method for quantifying foot-and-mouth disease viral RNA. J Virol Methods. 2009, 155: 150-156. 10.1016/j.jviromet.2008.10.007.CrossRefPubMed Huang X, Li Y, Zheng C: A novel single-cell quantitative real-time RT-PCR method for quantifying foot-and-mouth disease viral RNA. J Virol Methods. 2009, 155: 150-156. 10.1016/j.jviromet.2008.10.007.CrossRefPubMed
28.
go back to reference Li Y, Huang X, Xia B, Zheng C: Development and validation of a duplex quantitative real-time RT-PCR assay for simultaneous detection and quantitation of foot-and-mouth disease viral positive-stranded RNAs and negative-stranded RNAs. J Virol Methods. 2009, 161: 161-167. 10.1016/j.jviromet.2009.06.008.CrossRefPubMed Li Y, Huang X, Xia B, Zheng C: Development and validation of a duplex quantitative real-time RT-PCR assay for simultaneous detection and quantitation of foot-and-mouth disease viral positive-stranded RNAs and negative-stranded RNAs. J Virol Methods. 2009, 161: 161-167. 10.1016/j.jviromet.2009.06.008.CrossRefPubMed
29.
go back to reference Pelletier I, Duncan G, Pavio N, Colbère-Garapin F: Molecular mechanisms of poliovirus persistence: key role of capsid determinants during the establishment phase. Cell Mol Life Sci. 1998, 54: 1385-1402. 10.1007/s000180050261.CrossRefPubMed Pelletier I, Duncan G, Pavio N, Colbère-Garapin F: Molecular mechanisms of poliovirus persistence: key role of capsid determinants during the establishment phase. Cell Mol Life Sci. 1998, 54: 1385-1402. 10.1007/s000180050261.CrossRefPubMed
30.
go back to reference Martín-Acebes MA, González-Magaldi M, Sandvig K, Sobrino F, Armas-Portela R: Productive entry of type C foot-and-mouth disease virus into susceptible cultured cells requires clathrin and is dependent on the presense of plasma membrane cholesterol. Virology. 2007, 369: 105-118.CrossRefPubMed Martín-Acebes MA, González-Magaldi M, Sandvig K, Sobrino F, Armas-Portela R: Productive entry of type C foot-and-mouth disease virus into susceptible cultured cells requires clathrin and is dependent on the presense of plasma membrane cholesterol. Virology. 2007, 369: 105-118.CrossRefPubMed
31.
go back to reference Carrillo C, Tulman ER, Delhon G, Lu Z, Carreno A, Vagnozzi A, Kutish GF, Rock DL: Comparative genomics of foot-and-mouth disease virus. J Virol. 2005, 79: 6487-6504. 10.1128/JVI.79.10.6487-6504.2005.PubMedCentralCrossRefPubMed Carrillo C, Tulman ER, Delhon G, Lu Z, Carreno A, Vagnozzi A, Kutish GF, Rock DL: Comparative genomics of foot-and-mouth disease virus. J Virol. 2005, 79: 6487-6504. 10.1128/JVI.79.10.6487-6504.2005.PubMedCentralCrossRefPubMed
32.
go back to reference Nayak A, Goodfellow IG, Woolaway KE, Birtley J, Curry S, Belsham GJ: Role of RNA structure and RNA binding activity of Foot-and-Mouth disease virus 3C protein in VPg uridylylation and virus replication. J Virol. 2006, 80: 9865-9875. 10.1128/JVI.00561-06.PubMedCentralCrossRefPubMed Nayak A, Goodfellow IG, Woolaway KE, Birtley J, Curry S, Belsham GJ: Role of RNA structure and RNA binding activity of Foot-and-Mouth disease virus 3C protein in VPg uridylylation and virus replication. J Virol. 2006, 80: 9865-9875. 10.1128/JVI.00561-06.PubMedCentralCrossRefPubMed
33.
go back to reference Bachrach HL, Callis JJ, Hess WR, Patty RE: A plaque assay for foot-and-mouth disease virus and kinetics of virus reproduction. Virology. 1957, 4: 224-236. 10.1016/0042-6822(57)90060-0.CrossRefPubMed Bachrach HL, Callis JJ, Hess WR, Patty RE: A plaque assay for foot-and-mouth disease virus and kinetics of virus reproduction. Virology. 1957, 4: 224-236. 10.1016/0042-6822(57)90060-0.CrossRefPubMed
34.
go back to reference Li Y, Jousset FX, Giraud C, Rolling F, Quiot JM, Bergoin M: A titration procedure of the Junonia coenia densovirus and quantitation of transfection by its cloned genomic DNA in four lepidopteran cell lines. J Virol Methods. 1996, 57: 47-60. 10.1016/0166-0934(95)01961-8.CrossRefPubMed Li Y, Jousset FX, Giraud C, Rolling F, Quiot JM, Bergoin M: A titration procedure of the Junonia coenia densovirus and quantitation of transfection by its cloned genomic DNA in four lepidopteran cell lines. J Virol Methods. 1996, 57: 47-60. 10.1016/0166-0934(95)01961-8.CrossRefPubMed
Metadata
Title
Establishment of persistent infection with foot-and-mouth disease virus in BHK-21 cells
Authors
Xuan Huang
Yong Li
Hui Fang
Congyi Zheng
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Virology Journal / Issue 1/2011
Electronic ISSN: 1743-422X
DOI
https://doi.org/10.1186/1743-422X-8-169

Other articles of this Issue 1/2011

Virology Journal 1/2011 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.