Publication

Protein kinase A-dependent step(s) in hepatitis C virus entry and infectivity

Farquhar, M. J., Harris, H. J., Diskar, M., Jones, S., Mee, C. J., Nielsen, S. U., Brimacombe, C. L., Molina, S., Toms, G. L., Maurel, P., Howl, J., Herberg, F. W., van Ijzendoorn, S. C. D., Balfe, P. & McKeating, J. A., Sep-2008, In : Journal of Virology. 82, 17, p. 8797-8811 15 p.

Research output: Contribution to journalReview articleAcademicpeer-review

APA

Farquhar, M. J., Harris, H. J., Diskar, M., Jones, S., Mee, C. J., Nielsen, S. U., ... McKeating, J. A. (2008). Protein kinase A-dependent step(s) in hepatitis C virus entry and infectivity. Journal of Virology, 82(17), 8797-8811. https://doi.org/10.1128/JVI.00592-08

Author

Farquhar, Michelle J. ; Harris, Helen J. ; Diskar, Mandy ; Jones, Sarah ; Mee, Christopher J. ; Nielsen, Soren U. ; Brimacombe, Claire L. ; Molina, Sonia ; Toms, Geoffrey L. ; Maurel, Patrick ; Howl, John ; Herberg, Friedrich W. ; van Ijzendoorn, Sven C. D. ; Balfe, Peter ; McKeating, Jane A. / Protein kinase A-dependent step(s) in hepatitis C virus entry and infectivity. In: Journal of Virology. 2008 ; Vol. 82, No. 17. pp. 8797-8811.

Harvard

Farquhar, MJ, Harris, HJ, Diskar, M, Jones, S, Mee, CJ, Nielsen, SU, Brimacombe, CL, Molina, S, Toms, GL, Maurel, P, Howl, J, Herberg, FW, van Ijzendoorn, SCD, Balfe, P & McKeating, JA 2008, 'Protein kinase A-dependent step(s) in hepatitis C virus entry and infectivity', Journal of Virology, vol. 82, no. 17, pp. 8797-8811. https://doi.org/10.1128/JVI.00592-08

Standard

Protein kinase A-dependent step(s) in hepatitis C virus entry and infectivity. / Farquhar, Michelle J.; Harris, Helen J.; Diskar, Mandy; Jones, Sarah; Mee, Christopher J.; Nielsen, Soren U.; Brimacombe, Claire L.; Molina, Sonia; Toms, Geoffrey L.; Maurel, Patrick; Howl, John; Herberg, Friedrich W.; van Ijzendoorn, Sven C. D.; Balfe, Peter; McKeating, Jane A.

In: Journal of Virology, Vol. 82, No. 17, 09.2008, p. 8797-8811.

Research output: Contribution to journalReview articleAcademicpeer-review

Vancouver

Farquhar MJ, Harris HJ, Diskar M, Jones S, Mee CJ, Nielsen SU et al. Protein kinase A-dependent step(s) in hepatitis C virus entry and infectivity. Journal of Virology. 2008 Sep;82(17):8797-8811. https://doi.org/10.1128/JVI.00592-08


BibTeX

@article{4b53d9c3f02c48d48143c1fb3df1bbdb,
title = "Protein kinase A-dependent step(s) in hepatitis C virus entry and infectivity",
abstract = "Viruses exploit signaling pathways to their advantage during multiple stages of their life cycle. We demonstrate a role for protein kinase A (PKA) in the hepatitis C virus (HCV) life cycle. The inhibition of PKA with H89, cyclic AMP (cAMP) antagonists, or the protein kinase inhibitor peptide reduced HCV entry into Huh-7.5 hepatoma cells. Bioluminescence resonance energy transfer methodology allowed us to investigate the PKA isoform specificity of the cAMP antagonists in Huh-7.5 cells, suggesting a role for PKA type 11 in HCV internalization. Since viral entry is dependent on the host cell expression of CD81, scavenger receptor BI, and claudin-1 (CLDN1), we studied the role of PKA in regulating viral receptor localization by confocal imaging and fluorescence resonance energy transfer (FRET) analysis. Inhibiting PKA activity in Huh-7.5 cells induced a reorganization of CLDN1 from the plasma membrane to an intracellular vesicular location(s) and disrupted FRET between CLDN1 and CD81, demonstrating the importance of CLDN1 expression at the plasma membrane for viral receptor activity. Inhibiting PKA activity in Huh-7.5 cells reduced the infectivity of extracellular virus without modulating the level of cell-free HCV RNA, suggesting that particle secretion was not affected but that specific infectivity was reduced. Viral particles released from H89-treated cells displayed the same range of buoyant densities as did those from control cells, suggesting that viral protein association with lipoproteins is not regulated by PKA. HCV infection of Huh-7.5 cells increased cAMP levels and phosphorylated PKA substrates, supporting a model where infection activates PKA in a cAMP-dependent manner to promote virus release and transmission.",
keywords = "POLARIZED SPHINGOLIPID TRANSPORT, JUNCTION BARRIER FUNCTION, OVARIAN-CANCER CELLS, ENERGY-TRANSFER BRET, B TYPE-I, TIGHT-JUNCTION, CYCLIC-AMP, SCAVENGER RECEPTOR, CATALYTIC SUBUNIT, SUBAPICAL COMPARTMENT",
author = "Farquhar, {Michelle J.} and Harris, {Helen J.} and Mandy Diskar and Sarah Jones and Mee, {Christopher J.} and Nielsen, {Soren U.} and Brimacombe, {Claire L.} and Sonia Molina and Toms, {Geoffrey L.} and Patrick Maurel and John Howl and Herberg, {Friedrich W.} and {van Ijzendoorn}, {Sven C. D.} and Peter Balfe and McKeating, {Jane A.}",
year = "2008",
month = "9",
doi = "10.1128/JVI.00592-08",
language = "English",
volume = "82",
pages = "8797--8811",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "17",

}

RIS

TY - JOUR

T1 - Protein kinase A-dependent step(s) in hepatitis C virus entry and infectivity

AU - Farquhar, Michelle J.

AU - Harris, Helen J.

AU - Diskar, Mandy

AU - Jones, Sarah

AU - Mee, Christopher J.

AU - Nielsen, Soren U.

AU - Brimacombe, Claire L.

AU - Molina, Sonia

AU - Toms, Geoffrey L.

AU - Maurel, Patrick

AU - Howl, John

AU - Herberg, Friedrich W.

AU - van Ijzendoorn, Sven C. D.

AU - Balfe, Peter

AU - McKeating, Jane A.

PY - 2008/9

Y1 - 2008/9

N2 - Viruses exploit signaling pathways to their advantage during multiple stages of their life cycle. We demonstrate a role for protein kinase A (PKA) in the hepatitis C virus (HCV) life cycle. The inhibition of PKA with H89, cyclic AMP (cAMP) antagonists, or the protein kinase inhibitor peptide reduced HCV entry into Huh-7.5 hepatoma cells. Bioluminescence resonance energy transfer methodology allowed us to investigate the PKA isoform specificity of the cAMP antagonists in Huh-7.5 cells, suggesting a role for PKA type 11 in HCV internalization. Since viral entry is dependent on the host cell expression of CD81, scavenger receptor BI, and claudin-1 (CLDN1), we studied the role of PKA in regulating viral receptor localization by confocal imaging and fluorescence resonance energy transfer (FRET) analysis. Inhibiting PKA activity in Huh-7.5 cells induced a reorganization of CLDN1 from the plasma membrane to an intracellular vesicular location(s) and disrupted FRET between CLDN1 and CD81, demonstrating the importance of CLDN1 expression at the plasma membrane for viral receptor activity. Inhibiting PKA activity in Huh-7.5 cells reduced the infectivity of extracellular virus without modulating the level of cell-free HCV RNA, suggesting that particle secretion was not affected but that specific infectivity was reduced. Viral particles released from H89-treated cells displayed the same range of buoyant densities as did those from control cells, suggesting that viral protein association with lipoproteins is not regulated by PKA. HCV infection of Huh-7.5 cells increased cAMP levels and phosphorylated PKA substrates, supporting a model where infection activates PKA in a cAMP-dependent manner to promote virus release and transmission.

AB - Viruses exploit signaling pathways to their advantage during multiple stages of their life cycle. We demonstrate a role for protein kinase A (PKA) in the hepatitis C virus (HCV) life cycle. The inhibition of PKA with H89, cyclic AMP (cAMP) antagonists, or the protein kinase inhibitor peptide reduced HCV entry into Huh-7.5 hepatoma cells. Bioluminescence resonance energy transfer methodology allowed us to investigate the PKA isoform specificity of the cAMP antagonists in Huh-7.5 cells, suggesting a role for PKA type 11 in HCV internalization. Since viral entry is dependent on the host cell expression of CD81, scavenger receptor BI, and claudin-1 (CLDN1), we studied the role of PKA in regulating viral receptor localization by confocal imaging and fluorescence resonance energy transfer (FRET) analysis. Inhibiting PKA activity in Huh-7.5 cells induced a reorganization of CLDN1 from the plasma membrane to an intracellular vesicular location(s) and disrupted FRET between CLDN1 and CD81, demonstrating the importance of CLDN1 expression at the plasma membrane for viral receptor activity. Inhibiting PKA activity in Huh-7.5 cells reduced the infectivity of extracellular virus without modulating the level of cell-free HCV RNA, suggesting that particle secretion was not affected but that specific infectivity was reduced. Viral particles released from H89-treated cells displayed the same range of buoyant densities as did those from control cells, suggesting that viral protein association with lipoproteins is not regulated by PKA. HCV infection of Huh-7.5 cells increased cAMP levels and phosphorylated PKA substrates, supporting a model where infection activates PKA in a cAMP-dependent manner to promote virus release and transmission.

KW - POLARIZED SPHINGOLIPID TRANSPORT

KW - JUNCTION BARRIER FUNCTION

KW - OVARIAN-CANCER CELLS

KW - ENERGY-TRANSFER BRET

KW - B TYPE-I

KW - TIGHT-JUNCTION

KW - CYCLIC-AMP

KW - SCAVENGER RECEPTOR

KW - CATALYTIC SUBUNIT

KW - SUBAPICAL COMPARTMENT

U2 - 10.1128/JVI.00592-08

DO - 10.1128/JVI.00592-08

M3 - Review article

VL - 82

SP - 8797

EP - 8811

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 17

ER -

ID: 4766515