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Updated: Jul 1, 2026
MicroRNA-based Regulation of Picornavirus Tropism
Published on: February 6, 2017
Toll-like receptor 3 activation decreases porcine arterivirus infection
Yongming Sang1, Chris R Ross, Raymond R R Rowland
1Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University 66506-5802, Manhattan, Kansas, USA.
Abstract:
Porcine reproductive and respiratory syndrome virus (PRRSV) is an RNA virus that initiates infection in pulmonary alveolar macrophages (PAMs), elicits weak immune responses, and establishes a persistent infection. To understand the role of dsRNA intermediates in eliciting host immunity, we sought to determine if toll-like receptor-3 (TLR3), a well-known dsRNA sensor, is involved in the regulation of PRRSV infection. TLR3 gene expression was increased in PAMs of congenitally infected 2-wk-old pigs. Stimulation of PAMs with dsRNA increased gene expression for TLR3 and interferon-beta and suppressed PRRSV infectivity. To investigate activation and signaling parameters, expression constructs of wild-type and functional-domain-truncated porcine TLR3 were used in cell transfection studies. When cells that overexpressed porcine TLR3 were stimulated with dsRNA a rapid and robust calcium influx was induced. Moreover, ligand activation of porcine TLR3 expressed in MARC-145 cells elicited an antiviral response to PRRSV. Conversely, transfection of PAMs with small-interfering RNA targeting porcine TLR3 resulted in up to 80% suppression of TLR3 mRNA expression and an increase in PRRSV infectivity. These data provide fundamental genetic and molecular information for porcine TLR3, and implicate its involvement in PRRSV infection, findings that may suggest new strategies to limit this costly pandemic disease.
Insights
Toll-like receptor-3 (TLR3) plays a crucial role in regulating porcine reproductive and respiratory syndrome virus (PRRSV) infection. Activating TLR3 enhances the immune response against PRRSV, offering potential new disease control strategies.
Area of Science:
- Immunology
- Virology
- Molecular Biology
Background:
- Porcine reproductive and respiratory syndrome virus (PRRSV) causes persistent infections with weak immune responses.
- Double-stranded RNA (dsRNA) intermediates are involved in eliciting host immunity.
- Toll-like receptor-3 (TLR3) is a known sensor for dsRNA.
Purpose of the Study:
- To investigate the role of toll-like receptor-3 (TLR3) in regulating porcine reproductive and respiratory syndrome virus (PRRSV) infection.
- To understand the molecular mechanisms of TLR3 activation and signaling in response to dsRNA in pigs.
Main Methods:
- Gene expression analysis of TLR3 and interferon-beta in porcine alveolar macrophages (PAMs).
- Stimulation of PAMs with dsRNA and PRRSV.
- Cell transfection studies using wild-type and truncated porcine TLR3 constructs.
- Small interfering RNA (siRNA) mediated knockdown of TLR3 in PAMs.
Main Results:
- TLR3 gene expression increased in PRRSV-infected pigs.
- dsRNA stimulation upregulated TLR3 and interferon-beta, suppressing PRRSV infectivity.
- Overexpression of porcine TLR3 induced calcium influx upon dsRNA stimulation.
- Ligand activation of porcine TLR3 conferred antiviral response to PRRSV.
- TLR3 knockdown increased PRRSV infectivity.
Conclusions:
- Porcine TLR3 is involved in the innate immune response against PRRSV.
- TLR3 activation by dsRNA can suppress PRRSV infection.
- Findings provide insights into porcine TLR3 function and suggest potential therapeutic strategies against PRRSV.
