New Insights to Adenovirus-Directed Innate Immunity in Respiratory Epithelial Cells

The nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) family of transcription factors is a key component of the host innate immune response to infectious adenoviruses and adenovirus vectors. In this review, we will discuss a regulatory adenoviral protein encoded by early...

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Main Author: Cathleen R. Carlin
Format: Article
Language:English
Published: MDPI AG 2019-07-01
Series:Microorganisms
Subjects:
Online Access:https://www.mdpi.com/2076-2607/7/8/216
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author Cathleen R. Carlin
author_facet Cathleen R. Carlin
author_sort Cathleen R. Carlin
collection DOAJ
description The nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) family of transcription factors is a key component of the host innate immune response to infectious adenoviruses and adenovirus vectors. In this review, we will discuss a regulatory adenoviral protein encoded by early region 3 (E3) called E3-RIDα, which targets NFκB through subversion of novel host cell pathways. E3-RIDα down-regulates an EGF receptor signaling pathway, which overrides NFκB negative feedback control in the nucleus, and is induced by cell stress associated with viral infection and exposure to the pro-inflammatory cytokine TNF-α. E3-RIDα also modulates NFκB signaling downstream of the lipopolysaccharide receptor, Toll-like receptor 4, through formation of membrane contact sites controlling cholesterol levels in endosomes. These innate immune evasion tactics have yielded unique perspectives regarding the potential physiological functions of host cell pathways with important roles in infectious disease.
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spelling doaj.art-d3501c7bcd0347f6968bb32d69eb79e92022-12-21T20:31:46ZengMDPI AGMicroorganisms2076-26072019-07-017821610.3390/microorganisms7080216microorganisms7080216New Insights to Adenovirus-Directed Innate Immunity in Respiratory Epithelial CellsCathleen R. Carlin0Department of Molecular Biology and Microbiology and the Case Comprehensive Cancer Center, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USAThe nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) family of transcription factors is a key component of the host innate immune response to infectious adenoviruses and adenovirus vectors. In this review, we will discuss a regulatory adenoviral protein encoded by early region 3 (E3) called E3-RIDα, which targets NFκB through subversion of novel host cell pathways. E3-RIDα down-regulates an EGF receptor signaling pathway, which overrides NFκB negative feedback control in the nucleus, and is induced by cell stress associated with viral infection and exposure to the pro-inflammatory cytokine TNF-α. E3-RIDα also modulates NFκB signaling downstream of the lipopolysaccharide receptor, Toll-like receptor 4, through formation of membrane contact sites controlling cholesterol levels in endosomes. These innate immune evasion tactics have yielded unique perspectives regarding the potential physiological functions of host cell pathways with important roles in infectious disease.https://www.mdpi.com/2076-2607/7/8/216adenovirusearly region 3innate immunityNFκB
spellingShingle Cathleen R. Carlin
New Insights to Adenovirus-Directed Innate Immunity in Respiratory Epithelial Cells
Microorganisms
adenovirus
early region 3
innate immunity
NFκB
title New Insights to Adenovirus-Directed Innate Immunity in Respiratory Epithelial Cells
title_full New Insights to Adenovirus-Directed Innate Immunity in Respiratory Epithelial Cells
title_fullStr New Insights to Adenovirus-Directed Innate Immunity in Respiratory Epithelial Cells
title_full_unstemmed New Insights to Adenovirus-Directed Innate Immunity in Respiratory Epithelial Cells
title_short New Insights to Adenovirus-Directed Innate Immunity in Respiratory Epithelial Cells
title_sort new insights to adenovirus directed innate immunity in respiratory epithelial cells
topic adenovirus
early region 3
innate immunity
NFκB
url https://www.mdpi.com/2076-2607/7/8/216
work_keys_str_mv AT cathleenrcarlin newinsightstoadenovirusdirectedinnateimmunityinrespiratoryepithelialcells