東華大學圖書館 |

Language: English

Help

回圖書館首頁

手機版館藏查詢

Back

Switch To: Labeled | MARC Mode | ISBD

The Functions of Autophagy Genes and...

Maloney, Nicole Samantha.

Linked to FindBook

Google Book

Amazon

博客來

The Functions of Autophagy Genes and Interferon Regulatory Factor 1 in Interferon Gamma Mediated Control of Murine Norovirus Infection.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	The Functions of Autophagy Genes and Interferon Regulatory Factor 1 in Interferon Gamma Mediated Control of Murine Norovirus Infection./
Author:	Maloney, Nicole Samantha.
Description:	140 p.
Notes:	Source: Dissertation Abstracts International, Volume: 74-07(E), Section: B.
Contained By:	Dissertation Abstracts International74-07B(E).
Subject:	Biology, Genetics. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3557013
ISBN:	9781267995919

The Functions of Autophagy Genes and Interferon Regulatory Factor 1 in Interferon Gamma Mediated Control of Murine Norovirus Infection.
Maloney, Nicole Samantha.

The Functions of Autophagy Genes and Interferon Regulatory Factor 1 in Interferon Gamma Mediated Control of Murine Norovirus Infection. - 140 p.

Source: Dissertation Abstracts International, Volume: 74-07(E), Section: B.

Thesis (Ph.D.)--Washington University in St. Louis, 2013.

Human noroviruses (HuNVs) account for the majority of the non-bacterial gastroenteritis worldwide. Symptoms of HuNV infection are generally self-limiting and typically resolve within 72 hrs implicating innate immune mechanisms in their control. Interferons (IFNs) are central to early host defense and are likely involved in restricting HuNV infection. However, in the absence of a culturable HuNV, studies of the immune mechanisms that restrict HuNV replication are limited. To study the role of IFNs, in particular interferon gamma, (IFNγ) and the antiviral machinery they employ to control norovirus (NV) infection, we utilized murine norovirus (MNV) as a model of NV pathogenesis and IFN-mediated control. We found that the autophagy proteins, Atg 5, 7 and 16 are important for control of MNV by IFNγ in macrophages. These proteins are best known as essential participants in macroautophapy (herein autophagy) which is the process by which cells engulf and digest self components. Here, we demonstrate that the action of these molecules in control of MNV represent a non-canonical function of these proteins. Furthermore, we have shown that IFNγ acts downstream of initial viral protein translation but upstream of replication of the viral genomes in an Atg5 dependent manner. Moreover we confirmed the in vivo relevance of Atg5-mediated IFNγ effects. Furthermore, we found that the transcription factor, interferon regulatory factor (IRF-1), was important for control of MNV replication in vivo and required for IFNγ mediated inhibition of MNV in cultured cells. Despite reported roles of IRF-1 in coordinating type I IFN induction and action, we establish that IFNγ mediated inhibition of MNV was IRF-1 dependent but IFNα/β independent. Furthermore, we have used microarray analyses to identify genes that are transcriptionally regulated by STAT-1 and IRF-1 and which we speculate contribute to IFNγ direct antiviral effects. These studies identify a novel IFNγ-mediated antiviral mechanism involving autophagy proteins. Furthermore, they demonstrate a role of IRF-1 in control of MNV infection and provide new targets for investigation that may further elucidate the molecular mechanisms of IFNγ direct antiviral effects.

ISBN: 9781267995919Subjects--Topical Terms:

1017730
Biology, Genetics.

The Functions of Autophagy Genes and Interferon Regulatory Factor 1 in Interferon Gamma Mediated Control of Murine Norovirus Infection.
LDR:03532nam 2200349 4500 001 1957167
005 20131112081706.5
008 150210s2013 ||||||||||||||||| ||eng d
020 $a 9781267995919
035 $a (UMI)AAI3557013
035 $a AAI3557013
040 $a UMI $c UMI
100 1 $a Maloney, Nicole Samantha. $3 2092001
245 1 4 $a The Functions of Autophagy Genes and Interferon Regulatory Factor 1 in Interferon Gamma Mediated Control of Murine Norovirus Infection.
300 $a 140 p.
500 $a Source: Dissertation Abstracts International, Volume: 74-07(E), Section: B.
500 $a Adviser: Herbert W. Virgin.
502 $a Thesis (Ph.D.)--Washington University in St. Louis, 2013.
520 $a Human noroviruses (HuNVs) account for the majority of the non-bacterial gastroenteritis worldwide. Symptoms of HuNV infection are generally self-limiting and typically resolve within 72 hrs implicating innate immune mechanisms in their control. Interferons (IFNs) are central to early host defense and are likely involved in restricting HuNV infection. However, in the absence of a culturable HuNV, studies of the immune mechanisms that restrict HuNV replication are limited. To study the role of IFNs, in particular interferon gamma, (IFNγ) and the antiviral machinery they employ to control norovirus (NV) infection, we utilized murine norovirus (MNV) as a model of NV pathogenesis and IFN-mediated control. We found that the autophagy proteins, Atg 5, 7 and 16 are important for control of MNV by IFNγ in macrophages. These proteins are best known as essential participants in macroautophapy (herein autophagy) which is the process by which cells engulf and digest self components. Here, we demonstrate that the action of these molecules in control of MNV represent a non-canonical function of these proteins. Furthermore, we have shown that IFNγ acts downstream of initial viral protein translation but upstream of replication of the viral genomes in an Atg5 dependent manner. Moreover we confirmed the in vivo relevance of Atg5-mediated IFNγ effects. Furthermore, we found that the transcription factor, interferon regulatory factor (IRF-1), was important for control of MNV replication in vivo and required for IFNγ mediated inhibition of MNV in cultured cells. Despite reported roles of IRF-1 in coordinating type I IFN induction and action, we establish that IFNγ mediated inhibition of MNV was IRF-1 dependent but IFNα/β independent. Furthermore, we have used microarray analyses to identify genes that are transcriptionally regulated by STAT-1 and IRF-1 and which we speculate contribute to IFNγ direct antiviral effects. These studies identify a novel IFNγ-mediated antiviral mechanism involving autophagy proteins. Furthermore, they demonstrate a role of IRF-1 in control of MNV infection and provide new targets for investigation that may further elucidate the molecular mechanisms of IFNγ direct antiviral effects.
590 $a School code: 0252.
650 4 $a Biology, Genetics. $3 1017730
650 4 $a Biology, Virology. $3 1019068
650 4 $a Health Sciences, Immunology. $3 1017716
690 $a 0369
690 $a 0720
690 $a 0982
710 2 $a Washington University in St. Louis. $b Biology & Biomedical Sciences (Immunology). $3 2091994
773 0 $t Dissertation Abstracts International $g 74-07B(E).
790 1 0 $a Virgin, Herbert W., $e advisor
790 1 0 $a Colonna, Marco $e committee member
790 1 0 $a Diamond, Michael $e committee member
790 1 0 $a Lenschow, Deborah $e committee member
790 1 0 $a Schreiber, Robert $e committee member
790 1 0 $a Stappenbeck, Thaddeus $e committee member
790 $a 0252
791 $a Ph.D.
792 $a 2013
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3557013