Rhinovirus upregulates transient receptor potential channels in a human neuronal cell line: Implications for respiratory virus-induced cough reflex sensitivity: implications for respiratory virus-induced cough reflex sensitivity

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Abstract

Background: The mechanism underlying respiratory virus-induced cough hypersensitivity is unknown. Upregulation of airway neuronal receptors responsible for sensing physical and chemical stimuli is one possibility, and the transient receptor potential (TRP) channel family are potential candidates. We have used an in vitro model of sensory neurons and human rhinovirus (HRV-16) to study the effect of virus infection on TRP expression.

Methods: IMR-32 neuroblastoma cells were differentiated in culture to express three TRP channels: TRPV1, TRPA1 and TRPM8. Flow cytometry and qRT-PCR were used to measure TRP channel protein and mRNA levels following inoculation with live virus, inactivated virus, virus-induced soluble factors or pelleted virus particles. Multiplex bioassay was used to determine nerve growth factor (NGF), interleukin (IL)-1β, IL-6 and IL-8 levels in response to infection.

Results: Early upregulation of TRPA1 and TRPV1 expression occurred 2–4 h post infection. This was independent of replicating virus as virus-induced soluble factors alone were sufficient to increase channel expression 50-fold and 15-fold, respectively. NGF, IL-6 and IL-8 levels, increased in infected cell supernatants, represent possible candidates. In contrast, TRPM8 expression was maximal at 48 h (9.6-fold) and required virus replication rather than soluble factors.

Conclusions: We show for the first time that rhinovirus can infect neuronal cells. Furthermore, infection causes upregulation of TRP channels by channel-specific mechanisms. The increase in TRPA1 and TRPV1 levels can be mediated by soluble factors induced by infection whereas TRPM8 requires replicating virus. TRP channels may be novel therapeutic targets for controlling virus-induced cough.
Original languageEnglish
Pages (from-to)46-54
Number of pages9
JournalThorax
Volume69
Issue number1
Early online date03 Sep 2013
DOIs
Publication statusPublished - 12 Dec 2013

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Transient Receptor Potential Channels
Rhinovirus
Cough
Reflex
Up-Regulation
Viruses
Cell Line
Nerve Growth Factor
Infection
Interleukin-8
Interleukin-6
Sensory Receptor Cells
Virus Diseases
Virus Replication
Neuroblastoma
Interleukin-1
Biological Assay
Virion
Flow Cytometry
Hypersensitivity

Keywords

  • Calcium Channels/physiology
  • Cell Line
  • Cough/physiopathology
  • Flow Cytometry
  • Humans
  • Nerve Tissue Proteins/physiology
  • Neuroblastoma
  • Picornaviridae Infections
  • Respiratory Tract Infections/physiopathology
  • Rhinovirus/physiology
  • TRPA1 Cation Channel
  • TRPM Cation Channels/physiology
  • TRPV Cation Channels/physiology
  • Transient Receptor Potential Channels/physiology
  • Tumor Cells, Cultured
  • Up-Regulation/physiology
  • Virus Diseases/physiopathology
  • Virus Replication/physiology

Cite this

@article{d8684ca105a0468f9b5e77a81dd23511,
title = "Rhinovirus upregulates transient receptor potential channels in a human neuronal cell line: Implications for respiratory virus-induced cough reflex sensitivity: implications for respiratory virus-induced cough reflex sensitivity",
abstract = "Background: The mechanism underlying respiratory virus-induced cough hypersensitivity is unknown. Upregulation of airway neuronal receptors responsible for sensing physical and chemical stimuli is one possibility, and the transient receptor potential (TRP) channel family are potential candidates. We have used an in vitro model of sensory neurons and human rhinovirus (HRV-16) to study the effect of virus infection on TRP expression.Methods: IMR-32 neuroblastoma cells were differentiated in culture to express three TRP channels: TRPV1, TRPA1 and TRPM8. Flow cytometry and qRT-PCR were used to measure TRP channel protein and mRNA levels following inoculation with live virus, inactivated virus, virus-induced soluble factors or pelleted virus particles. Multiplex bioassay was used to determine nerve growth factor (NGF), interleukin (IL)-1β, IL-6 and IL-8 levels in response to infection.Results: Early upregulation of TRPA1 and TRPV1 expression occurred 2–4 h post infection. This was independent of replicating virus as virus-induced soluble factors alone were sufficient to increase channel expression 50-fold and 15-fold, respectively. NGF, IL-6 and IL-8 levels, increased in infected cell supernatants, represent possible candidates. In contrast, TRPM8 expression was maximal at 48 h (9.6-fold) and required virus replication rather than soluble factors.Conclusions: We show for the first time that rhinovirus can infect neuronal cells. Furthermore, infection causes upregulation of TRP channels by channel-specific mechanisms. The increase in TRPA1 and TRPV1 levels can be mediated by soluble factors induced by infection whereas TRPM8 requires replicating virus. TRP channels may be novel therapeutic targets for controlling virus-induced cough.",
keywords = "Calcium Channels/physiology, Cell Line, Cough/physiopathology, Flow Cytometry, Humans, Nerve Tissue Proteins/physiology, Neuroblastoma, Picornaviridae Infections, Respiratory Tract Infections/physiopathology, Rhinovirus/physiology, TRPA1 Cation Channel, TRPM Cation Channels/physiology, TRPV Cation Channels/physiology, Transient Receptor Potential Channels/physiology, Tumor Cells, Cultured, Up-Regulation/physiology, Virus Diseases/physiopathology, Virus Replication/physiology",
author = "H. Abdullah and L.G. Heaney and S.L. Cosby and L.P.A. McGarvey",
year = "2013",
month = "12",
day = "12",
doi = "10.1136/thoraxjnl-2013-203894",
language = "English",
volume = "69",
pages = "46--54",
journal = "Thorax",
issn = "0040-6376",
publisher = "BMJ Publishing Group",
number = "1",

}

TY - JOUR

T1 - Rhinovirus upregulates transient receptor potential channels in a human neuronal cell line: Implications for respiratory virus-induced cough reflex sensitivity: implications for respiratory virus-induced cough reflex sensitivity

AU - Abdullah, H.

AU - Heaney, L.G.

AU - Cosby, S.L.

AU - McGarvey, L.P.A.

PY - 2013/12/12

Y1 - 2013/12/12

N2 - Background: The mechanism underlying respiratory virus-induced cough hypersensitivity is unknown. Upregulation of airway neuronal receptors responsible for sensing physical and chemical stimuli is one possibility, and the transient receptor potential (TRP) channel family are potential candidates. We have used an in vitro model of sensory neurons and human rhinovirus (HRV-16) to study the effect of virus infection on TRP expression.Methods: IMR-32 neuroblastoma cells were differentiated in culture to express three TRP channels: TRPV1, TRPA1 and TRPM8. Flow cytometry and qRT-PCR were used to measure TRP channel protein and mRNA levels following inoculation with live virus, inactivated virus, virus-induced soluble factors or pelleted virus particles. Multiplex bioassay was used to determine nerve growth factor (NGF), interleukin (IL)-1β, IL-6 and IL-8 levels in response to infection.Results: Early upregulation of TRPA1 and TRPV1 expression occurred 2–4 h post infection. This was independent of replicating virus as virus-induced soluble factors alone were sufficient to increase channel expression 50-fold and 15-fold, respectively. NGF, IL-6 and IL-8 levels, increased in infected cell supernatants, represent possible candidates. In contrast, TRPM8 expression was maximal at 48 h (9.6-fold) and required virus replication rather than soluble factors.Conclusions: We show for the first time that rhinovirus can infect neuronal cells. Furthermore, infection causes upregulation of TRP channels by channel-specific mechanisms. The increase in TRPA1 and TRPV1 levels can be mediated by soluble factors induced by infection whereas TRPM8 requires replicating virus. TRP channels may be novel therapeutic targets for controlling virus-induced cough.

AB - Background: The mechanism underlying respiratory virus-induced cough hypersensitivity is unknown. Upregulation of airway neuronal receptors responsible for sensing physical and chemical stimuli is one possibility, and the transient receptor potential (TRP) channel family are potential candidates. We have used an in vitro model of sensory neurons and human rhinovirus (HRV-16) to study the effect of virus infection on TRP expression.Methods: IMR-32 neuroblastoma cells were differentiated in culture to express three TRP channels: TRPV1, TRPA1 and TRPM8. Flow cytometry and qRT-PCR were used to measure TRP channel protein and mRNA levels following inoculation with live virus, inactivated virus, virus-induced soluble factors or pelleted virus particles. Multiplex bioassay was used to determine nerve growth factor (NGF), interleukin (IL)-1β, IL-6 and IL-8 levels in response to infection.Results: Early upregulation of TRPA1 and TRPV1 expression occurred 2–4 h post infection. This was independent of replicating virus as virus-induced soluble factors alone were sufficient to increase channel expression 50-fold and 15-fold, respectively. NGF, IL-6 and IL-8 levels, increased in infected cell supernatants, represent possible candidates. In contrast, TRPM8 expression was maximal at 48 h (9.6-fold) and required virus replication rather than soluble factors.Conclusions: We show for the first time that rhinovirus can infect neuronal cells. Furthermore, infection causes upregulation of TRP channels by channel-specific mechanisms. The increase in TRPA1 and TRPV1 levels can be mediated by soluble factors induced by infection whereas TRPM8 requires replicating virus. TRP channels may be novel therapeutic targets for controlling virus-induced cough.

KW - Calcium Channels/physiology

KW - Cell Line

KW - Cough/physiopathology

KW - Flow Cytometry

KW - Humans

KW - Nerve Tissue Proteins/physiology

KW - Neuroblastoma

KW - Picornaviridae Infections

KW - Respiratory Tract Infections/physiopathology

KW - Rhinovirus/physiology

KW - TRPA1 Cation Channel

KW - TRPM Cation Channels/physiology

KW - TRPV Cation Channels/physiology

KW - Transient Receptor Potential Channels/physiology

KW - Tumor Cells, Cultured

KW - Up-Regulation/physiology

KW - Virus Diseases/physiopathology

KW - Virus Replication/physiology

U2 - 10.1136/thoraxjnl-2013-203894

DO - 10.1136/thoraxjnl-2013-203894

M3 - Article

C2 - 24002057

VL - 69

SP - 46

EP - 54

JO - Thorax

JF - Thorax

SN - 0040-6376

IS - 1

ER -