The Role of Tumor Necrosis Factor Alpha (TNF-a) In the Eyes and Brain of HSV-1 Infected Euthymic BALB/C Mice

Hdl Handle:
http://hdl.handle.net/10675.2/345265
Title:
The Role of Tumor Necrosis Factor Alpha (TNF-a) In the Eyes and Brain of HSV-1 Infected Euthymic BALB/C Mice
Authors:
Fields, Mark A
Abstract:
After uniocular anterior chamber (AC) inoculation of HSV-1, virus and TNFalpha (TNF-a) are detected in the eyes and brain o f HSV-1 infected euthymic BALB/c mice. The overall goal o f this study was to investigate the role o f TN F-a in the eyes and brain o f HSV-1 infected BALB/c mice. Mice were treated with thalidomide for TN F-a inhibition or injected with clodronate liposomes to deplete macrophages, and the AC of one eye (ipsilateral) was injected with HSV-1 (KOS). In thalidomide-treated mice, both suprachiasmatic nuclei (SCN) were infected by day 5 p.i. and the titer of virus in the SCN contralateral to the side o f injection was increased. In macrophage depleted mice, both SCN were infected at day 6 p.i. and the titer o f virus in the SCN o f these mice was increased at day 6 and 7 p.i. compared with controls. The titer o f virus in the contralateral (uninoculated) eye o f macrophage depleted mice was increased at day 7 p.i. The results o f these studies suggest that TN F-a plays a role in limiting virus replication in the SCN o f euthymic BALB/c mice and that one source of TN F-a is macrophages. In order to further investigate the role of TNF-a, a recombinant o f HSV-1 (KOS77VF) was constructed that produces TNF-a constitutively. Euthymic BALB/c mice were injected in one anterior chamber with the TNF-a recombinant, with a recombinant containing the pCI plasmid, with a recombinant rescue virus, or with the parental virus. Mice from each group were sacrificed on day 1-9 p.i. and the uninjected eyes were removed. In the uninjected eye o f KOSTNF -infected mice, TN F-a expression was increased and there were more viral antigen positive cells and immune inflammatory cells. There was earlier microscopic evidence o f retinal infection and destruction in these mice. In addition, the titer o f virus in the uninjected eye was significantly increased in KOSTiVF-infected mice on day 7 p.i. compared with KOSpCI, KOS6{irescue, or with KOS6/? infected mice. These results suggest that overproduction o f TN F-a by HSV-1 (KOS7WF) facilitates spread o f virus infection in the eye through increased inflammation and TNF-a-mediated damage to retinal cells.
Affiliation:
Not Listed
Issue Date:
Dec-2007
URI:
http://hdl.handle.net/10675.2/345265
Additional Links:
http://ezproxy.augusta.edu/login?url=http://search.proquest.com/docview/304786828?accountid=12365
Type:
Dissertation
Appears in Collections:
Theses and Dissertations

Full metadata record

DC FieldValue Language
dc.contributor.authorFields, Mark Aen
dc.date.accessioned2015-02-24T20:37:41Z-
dc.date.available2015-02-24T20:37:41Z-
dc.date.issued2007-12-
dc.identifier.urihttp://hdl.handle.net/10675.2/345265-
dc.description.abstractAfter uniocular anterior chamber (AC) inoculation of HSV-1, virus and TNFalpha (TNF-a) are detected in the eyes and brain o f HSV-1 infected euthymic BALB/c mice. The overall goal o f this study was to investigate the role o f TN F-a in the eyes and brain o f HSV-1 infected BALB/c mice. Mice were treated with thalidomide for TN F-a inhibition or injected with clodronate liposomes to deplete macrophages, and the AC of one eye (ipsilateral) was injected with HSV-1 (KOS). In thalidomide-treated mice, both suprachiasmatic nuclei (SCN) were infected by day 5 p.i. and the titer of virus in the SCN contralateral to the side o f injection was increased. In macrophage depleted mice, both SCN were infected at day 6 p.i. and the titer o f virus in the SCN o f these mice was increased at day 6 and 7 p.i. compared with controls. The titer o f virus in the contralateral (uninoculated) eye o f macrophage depleted mice was increased at day 7 p.i. The results o f these studies suggest that TN F-a plays a role in limiting virus replication in the SCN o f euthymic BALB/c mice and that one source of TN F-a is macrophages. In order to further investigate the role of TNF-a, a recombinant o f HSV-1 (KOS77VF) was constructed that produces TNF-a constitutively. Euthymic BALB/c mice were injected in one anterior chamber with the TNF-a recombinant, with a recombinant containing the pCI plasmid, with a recombinant rescue virus, or with the parental virus. Mice from each group were sacrificed on day 1-9 p.i. and the uninjected eyes were removed. In the uninjected eye o f KOSTNF -infected mice, TN F-a expression was increased and there were more viral antigen positive cells and immune inflammatory cells. There was earlier microscopic evidence o f retinal infection and destruction in these mice. In addition, the titer o f virus in the uninjected eye was significantly increased in KOSTiVF-infected mice on day 7 p.i. compared with KOSpCI, KOS6{irescue, or with KOS6/? infected mice. These results suggest that overproduction o f TN F-a by HSV-1 (KOS7WF) facilitates spread o f virus infection in the eye through increased inflammation and TNF-a-mediated damage to retinal cells.en
dc.relation.urlhttp://ezproxy.augusta.edu/login?url=http://search.proquest.com/docview/304786828?accountid=12365en
dc.rightsCopyright protected. Unauthorized reproduction or use beyond the exceptions granted by the Fair Use clause of U.S. Copyright law may violate federal law.en
dc.subjectCytokinesen
dc.subjectBrainen
dc.subjecteyeen
dc.subjectHerpesvirusen
dc.subjectImmunomodulatoren
dc.subjectSuprachiasmaticen
dc.subjectNucleusen
dc.subjectTNF-aen
dc.titleThe Role of Tumor Necrosis Factor Alpha (TNF-a) In the Eyes and Brain of HSV-1 Infected Euthymic BALB/C Miceen
dc.typeDissertationen
dc.contributor.departmentNot Listeden
dc.description.advisorAtherton, Sally S.en
dc.description.committeeCameron, Richard; Hamrick, Mark; McCluskey, Lynnette; Smith, Sylviaen
dc.description.degreeDoctor of Philosophy (Ph.D.)en
All Items in Scholarly Commons are protected by copyright, with all rights reserved, unless otherwise indicated.