Home Acta Virologica 2011 Acta Virologica Vol.55, No.3, p.243-253, 2011

Journal info


Quarterly, 72-88 pp. per issue
Founded: 1957
ISSN 0001-723X
E-ISSN 1336-2305

Published in English

Aims and Scope
Editorial Info

Abstracted and Indexed
Submission Guidelines

Select Journal







Webshop Cart

Your Cart is currently empty.

Info: Your browser does not accept cookies. To put products into your cart and purchase them you need to enable cookies.

Acta Virologica Vol.55, No.3, p.243-253, 2011

Title: Blockade of Lyn kinase upregulates both canonical and non-canonical TLR-3 pathways in THP-1 monocytes exposed to human cytomegalovirus
Author: K. H. YEW, C. J. HARRISON

Abstract: Regulation of monocyte response to human cytomegalovirus (HCMV) occurs via activation of receptors that elicit innate antiviral effects and later T-cell responses. Our previous data (Yew et al.., 2010) demonstrated that human monocyte scavenger receptor A type 1 (SR-A1) are required for sensing of HCMV by endosomal toll-like receptors (TLRs)-3 and -9, which in turn induce critical pro-inflammatory cytokines. However, it remains unclear which subcellular molecules associated with SR-A1 lead to downstream activation of TLR-3 and/or TLR-9 signaling pathways. Herein we report that Lyn kinase, associated physically and functionally with SR-A for low density lipoprotein (LDL) recognition, acts as a key SR-A1-induced kinase that plays a critical role in TLR-3/9 signal transduction upon HCMV exposure to THP-1 monocytes. We found that disruption of the SR-A1 signal transduction through molecular inhibition by Lyn kinase oligonucleotides not only blocks the activation of downstream TLR-9 pathway but also alters the downstream TLR-3 pathway. In particular, Lyn kinase oligonucleotides resulted in decreased expression of TLR-9-induced tumor necrosis factor alpha (TNF-α) but strongly upregulated canonical TLR-3-induced interferon beta (IFN-β) and non-canonical TLR-3-induced NF-κB-dependent p35 (35kDa) subunit of interleukin 12 (IL-12p35) gene transcription. Thus, the observed shift away from TNF-α to robust IFN-β and IL-12p35 induction may offer opportunities for therapeutic interventions.

Keywords: HCMV; THP-1 monocytes; TLR-3/-9; Lyn kinase; TNF-α; IFN-β; IL-12p35
Year: 2011, Volume: 55, Issue: 3 Page From: 243, Page To: 253
doi:10.4149/av_2011_03_243


download file



© AEPress s.r.o
Copyright notice: For any permission to reproduce, archive or otherwise use the documents in the ELiS, please contact AEP.