A dominant-negative mutant of rab5 inhibits infection of cells by foot-and-mouth disease virus: implications for virus entry

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Standard

A dominant-negative mutant of rab5 inhibits infection of cells by foot-and-mouth disease virus : implications for virus entry. / Johns, Helen L; Berryman, Stephen; Monaghan, Paul; Belsham, Graham J; Jackson, Terry.

In: Journal of Virology, Vol. 83, No. 12, 06.2009, p. 6247-56.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Johns, HL, Berryman, S, Monaghan, P, Belsham, GJ & Jackson, T 2009, 'A dominant-negative mutant of rab5 inhibits infection of cells by foot-and-mouth disease virus: implications for virus entry', Journal of Virology, vol. 83, no. 12, pp. 6247-56. https://doi.org/10.1128/JVI.02460-08

APA

Johns, H. L., Berryman, S., Monaghan, P., Belsham, G. J., & Jackson, T. (2009). A dominant-negative mutant of rab5 inhibits infection of cells by foot-and-mouth disease virus: implications for virus entry. Journal of Virology, 83(12), 6247-56. https://doi.org/10.1128/JVI.02460-08

Vancouver

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. Journal of Virology. 2009 Jun;83(12):6247-56. https://doi.org/10.1128/JVI.02460-08

Author

Johns, Helen L ; Berryman, Stephen ; Monaghan, Paul ; Belsham, Graham J ; Jackson, Terry. / A dominant-negative mutant of rab5 inhibits infection of cells by foot-and-mouth disease virus : implications for virus entry. In: Journal of Virology. 2009 ; Vol. 83, No. 12. pp. 6247-56.

Bibtex

@article{9958cb1c1faf495698c4750654e5576e,
title = "A dominant-negative mutant of rab5 inhibits infection of cells by foot-and-mouth disease virus: implications for virus entry",
abstract = "Foot-and-mouth disease virus (FMDV) can use a number of different integrins (alphavbeta1, alphavbeta3, alphavbeta6, and alphavbeta8) as receptors to initiate infection. Infection mediated by alphavbeta6 is known to occur by clathrin-mediated endocytosis and is dependent on the acidic pH within endosomes. On internalization, virus is detected rapidly in early endosomes (EE) and subsequently in perinuclear recycling endosomes (PNRE), but not in late endosomal compartments. Due to the extreme sensitivity of FMDV to acidic pH, it is thought that EE can provide a pH low enough for infection to occur; however, definitive proof that infection takes place from within these compartments is still lacking. Here we have investigated the intracellular transport steps required for FMDV infection of IBRS-2 cells, which express alphavbeta8 as their FMDV receptor. These experiments confirmed that FMDV infection mediated by alphavbeta8 is also dependent on clathrin-mediate endocytosis and an acidic pH within endosomes. Also, the effect on FMDV infection of dominant-negative (DN) mutants of cellular rab proteins that regulate endosomal traffic was examined. Expression of DN rab5 reduced the number of FMDV-infected cells by 80%, while expression of DN rab4 or DN rab7 had virtually no effect on infection. Expression of DN rab11 inhibited infection by FMDV, albeit to a small extent ( approximately 35%). These results demonstrate that FMDV infection takes place predominantly from within EE and does not require virus trafficking to the late endosomal compartments. However, our results suggest that infection may not be exclusive to EE and that a small amount of infection could occur from within PNRE.",
keywords = "Animals, Cells, Cultured, Clathrin/metabolism, Endosomes/virology, Foot-and-Mouth Disease/virology, Foot-and-Mouth Disease Virus/genetics, Hydrogen-Ion Concentration, Integrins/metabolism, Receptors, Virus/metabolism, Swine, Virus Internalization, rab5 GTP-Binding Proteins/genetics",
author = "Johns, {Helen L} and Stephen Berryman and Paul Monaghan and Belsham, {Graham J} and Terry Jackson",
year = "2009",
month = jun,
doi = "10.1128/JVI.02460-08",
language = "English",
volume = "83",
pages = "6247--56",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "12",

}

RIS

TY - JOUR

T1 - A dominant-negative mutant of rab5 inhibits infection of cells by foot-and-mouth disease virus

T2 - implications for virus entry

AU - Johns, Helen L

AU - Berryman, Stephen

AU - Monaghan, Paul

AU - Belsham, Graham J

AU - Jackson, Terry

PY - 2009/6

Y1 - 2009/6

N2 - Foot-and-mouth disease virus (FMDV) can use a number of different integrins (alphavbeta1, alphavbeta3, alphavbeta6, and alphavbeta8) as receptors to initiate infection. Infection mediated by alphavbeta6 is known to occur by clathrin-mediated endocytosis and is dependent on the acidic pH within endosomes. On internalization, virus is detected rapidly in early endosomes (EE) and subsequently in perinuclear recycling endosomes (PNRE), but not in late endosomal compartments. Due to the extreme sensitivity of FMDV to acidic pH, it is thought that EE can provide a pH low enough for infection to occur; however, definitive proof that infection takes place from within these compartments is still lacking. Here we have investigated the intracellular transport steps required for FMDV infection of IBRS-2 cells, which express alphavbeta8 as their FMDV receptor. These experiments confirmed that FMDV infection mediated by alphavbeta8 is also dependent on clathrin-mediate endocytosis and an acidic pH within endosomes. Also, the effect on FMDV infection of dominant-negative (DN) mutants of cellular rab proteins that regulate endosomal traffic was examined. Expression of DN rab5 reduced the number of FMDV-infected cells by 80%, while expression of DN rab4 or DN rab7 had virtually no effect on infection. Expression of DN rab11 inhibited infection by FMDV, albeit to a small extent ( approximately 35%). These results demonstrate that FMDV infection takes place predominantly from within EE and does not require virus trafficking to the late endosomal compartments. However, our results suggest that infection may not be exclusive to EE and that a small amount of infection could occur from within PNRE.

AB - Foot-and-mouth disease virus (FMDV) can use a number of different integrins (alphavbeta1, alphavbeta3, alphavbeta6, and alphavbeta8) as receptors to initiate infection. Infection mediated by alphavbeta6 is known to occur by clathrin-mediated endocytosis and is dependent on the acidic pH within endosomes. On internalization, virus is detected rapidly in early endosomes (EE) and subsequently in perinuclear recycling endosomes (PNRE), but not in late endosomal compartments. Due to the extreme sensitivity of FMDV to acidic pH, it is thought that EE can provide a pH low enough for infection to occur; however, definitive proof that infection takes place from within these compartments is still lacking. Here we have investigated the intracellular transport steps required for FMDV infection of IBRS-2 cells, which express alphavbeta8 as their FMDV receptor. These experiments confirmed that FMDV infection mediated by alphavbeta8 is also dependent on clathrin-mediate endocytosis and an acidic pH within endosomes. Also, the effect on FMDV infection of dominant-negative (DN) mutants of cellular rab proteins that regulate endosomal traffic was examined. Expression of DN rab5 reduced the number of FMDV-infected cells by 80%, while expression of DN rab4 or DN rab7 had virtually no effect on infection. Expression of DN rab11 inhibited infection by FMDV, albeit to a small extent ( approximately 35%). These results demonstrate that FMDV infection takes place predominantly from within EE and does not require virus trafficking to the late endosomal compartments. However, our results suggest that infection may not be exclusive to EE and that a small amount of infection could occur from within PNRE.

KW - Animals

KW - Cells, Cultured

KW - Clathrin/metabolism

KW - Endosomes/virology

KW - Foot-and-Mouth Disease/virology

KW - Foot-and-Mouth Disease Virus/genetics

KW - Hydrogen-Ion Concentration

KW - Integrins/metabolism

KW - Receptors, Virus/metabolism

KW - Swine

KW - Virus Internalization

KW - rab5 GTP-Binding Proteins/genetics

U2 - 10.1128/JVI.02460-08

DO - 10.1128/JVI.02460-08

M3 - Journal article

C2 - 19357169

VL - 83

SP - 6247

EP - 6256

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 12

ER -

ID: 257918238