INVESTIGATING THE ROLE OF NEWLY DESCRIBED CYTOSOLIC PATTERN RECOGNITION RECEPTORS IN PROTECTIVE HOST RESPONSES TO NEUROTROPIC VIRUSES

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Crill, E. (2014). INVESTIGATING THE ROLE OF NEWLY DESCRIBED CYTOSOLIC PATTERN RECOGNITION RECEPTORS IN PROTECTIVE HOST RESPONSES TO NEUROTROPIC VIRUSES. Unc Charlotte Electronic Theses And Dissertations.
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Abstract

The importance of the effector functions performed by glial cells, the resident cells of the CNS possessing immune functions, in abrogating potentially fatal neurotropic viral infections have only recently begun to gain appreciation. These effector functions would not be possible if it weren't for the presence of innate pattern recognition receptors (PRRs) that serve as sensors for conserved pathogenic components and initiate activation of innate defense mechanisms in response to a non-self invader. The current study investigates the role of retinoic acid inducible gene (RIG)-I and DNA-dependent activator of interferon regulatory factors (DAI) in the recognition and intervention against RNA and DNA viral infections in the glial cells, astrocytes and microglia. Our laboratory has previously shown that astrocytes and microglia express RIG-I and DAI and demonstrated that stimulation of these receptors with synthetic or virally-derived RNA or DNA ligands, respectively, leads to the expression and secretion of proinflammatory mediators. More recently, it has been hypothesized that the utilization of RNA polymerase III confers on RIG-I the ability to indirectly recognize and become activated by DNA pathogens. In the present study, we demonstrate that RNA polymerase III inhibition significantly attenuates protective host responses elicited following challenge with DNA, but not RNA, viruses and ligands. Inhibition of RNA polymerase III activity led to enhanced DNA, but not RNA, viral replication associated with reduced production of the potent antiviral molecule, interferon-beta (IFN-beta), suggesting that RNA polymerase III licenses RIG-I to mount protective immune responses against DNA pathogens.

Details
Author

Crill, Emma

Title

INVESTIGATING THE ROLE OF NEWLY DESCRIBED CYTOSOLIC PATTERN RECOGNITION RECEPTORS IN PROTECTIVE HOST RESPONSES TO NEUROTROPIC VIRUSES

Physical Description

1 online resource (81 pages) : PDF

Date

2014

Degree Granting Institution

University of North Carolina at Charlotte

Abstract

The importance of the effector functions performed by glial cells, the resident cells of the CNS possessing immune functions, in abrogating potentially fatal neurotropic viral infections have only recently begun to gain appreciation. These effector functions would not be possible if it weren't for the presence of innate pattern recognition receptors (PRRs) that serve as sensors for conserved pathogenic components and initiate activation of innate defense mechanisms in response to a non-self invader. The current study investigates the role of retinoic acid inducible gene (RIG)-I and DNA-dependent activator of interferon regulatory factors (DAI) in the recognition and intervention against RNA and DNA viral infections in the glial cells, astrocytes and microglia. Our laboratory has previously shown that astrocytes and microglia express RIG-I and DAI and demonstrated that stimulation of these receptors with synthetic or virally-derived RNA or DNA ligands, respectively, leads to the expression and secretion of proinflammatory mediators. More recently, it has been hypothesized that the utilization of RNA polymerase III confers on RIG-I the ability to indirectly recognize and become activated by DNA pathogens. In the present study, we demonstrate that RNA polymerase III inhibition significantly attenuates protective host responses elicited following challenge with DNA, but not RNA, viruses and ligands. Inhibition of RNA polymerase III activity led to enhanced DNA, but not RNA, viral replication associated with reduced production of the potent antiviral molecule, interferon-beta (IFN-beta), suggesting that RNA polymerase III licenses RIG-I to mount protective immune responses against DNA pathogens.

Genre

masters theses

Subjects--Topics

Immunology
Virology

Degree

M.S.

Keywords

CNS Inflammation
DAI
HSV-1
RIG-I
RNA Polymerase III
Type I Interferons

Subject Area

Biology

Advisor(s)

Marriott, Ian

Committee Members

Chauhan, Vinita
Grdzelishvili, Valery
Nelson, Daniel

Degree Note

Thesis (M.S.)--University of North Carolina at Charlotte, 2014.

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Rights Holder Information

Copyright is held by the author unless otherwise indicated.

Identifier

Crill_uncc_0694N_10702

Permalink

http://hdl.handle.net/20.500.13093/etd:1034