Cillo, Michele (2020) Adaptor protein CIKS is involved in STING-mediated antiviral innate immunity. [Tesi di dottorato]

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Item Type:	Tesi di dottorato
Lingua:	English
Title:	Adaptor protein CIKS is involved in STING-mediated antiviral innate immunity
Creators:	Creators Email Cillo, Michele michele.cillo@unina.it
Date:	13 March 2020
Number of Pages:	46
Institution:	Università degli Studi di Napoli Federico II
Department:	Medicina Molecolare e Biotecnologie Mediche
Dottorato:	Medicina molecolare e biotecnologie mediche
Ciclo di dottorato:	32
Coordinatore del Corso di dottorato:	nome email Avvedimento, Vittorio Enrico vittorioenrico.avvedimento@unina.it
Tutor:	nome email Leonardi, Antonio UNSPECIFIED
Date:	13 March 2020
Number of Pages:	46
Uncontrolled Keywords:	CIKS; STING; Antiviral immunity; Interferon
Settori scientifico-disciplinari del MIUR:	Area 06 - Scienze mediche > MED/04 - Patologia generale
Date Deposited:	25 Mar 2020 11:37
Last Modified:	08 Nov 2021 12:14
URI:	http://www.fedoa.unina.it/id/eprint/13152

Abstract

Innate immunity plays a critical role in controlling the early stage of a viral infection and its spread into the organism. The efficacy of innate immunity relies on a set of germ-line encoded receptors, belonging to the family of pattern recognition receptors (PRRs), that can bind conserved features of pathogens, collectively called pathogen-associated molecular patterns (PAMPs). In the case of viruses, PAMPs are mainly represented by their nucleic acids. Their recognition by numerous PRRs activates NF-B and IRF3 leading to the production and secretion of type I interferons (IFNs). By using as experimental model constituted by MEFs knock-out for CIKS, we show that the IL-17R adaptor protein CIKS is involved in this process. CIKS-/- cells produce and secrete lower amount of IFNβ when challenged by nucleic acids that mimic viral DNA or RNA (pA:T and pI:C respectively). This phenotype is reverted when FLAG-CIKS expression is restored in CIKS-/- cells by lentiviral transduction. IFNβ reduction is not due to alterations in its mRNA stability, rather to a differential phosphorylation of IRF3 between wt and CIKS-/- cells. We also found that wt and ΔUbox CIKS, but not E17A mutant, interacts with Stimulator of interferon genes (STING) and influences its ubiquitination via TRAF6. Moreover, this interaction is a consequence of viral stimulation, especially after DNA treatment. Here, we describe the role of CIKS in the STING-mediated antiviral signaling, its molecular interactors and the dynamics of this pathway.

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