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Investigations into the humoral and ...
~
Binder, Gwendolyn Knowlton.
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Investigations into the humoral and cellular mechanisms of alphavirus clearance from neurons in the central nervous system.
紀錄類型:
書目-語言資料,印刷品 : Monograph/item
正題名/作者:
Investigations into the humoral and cellular mechanisms of alphavirus clearance from neurons in the central nervous system./
作者:
Binder, Gwendolyn Knowlton.
面頁冊數:
161 p.
附註:
Adviser: Diane E. Griffin.
Contained By:
Dissertation Abstracts International63-03B.
標題:
Biology, Microbiology. -
電子資源:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3046421
ISBN:
0493605584
Investigations into the humoral and cellular mechanisms of alphavirus clearance from neurons in the central nervous system.
Binder, Gwendolyn Knowlton.
Investigations into the humoral and cellular mechanisms of alphavirus clearance from neurons in the central nervous system.
- 161 p.
Adviser: Diane E. Griffin.
Thesis (Ph.D.)--The Johns Hopkins University, 2002.
Together, the data presented in this work further our understanding of the mechanisms of virus clearance in the CNS, and establish IFN-γ as an important mediator of non-cytolytic clearance of virus from neurons in the CNS.
ISBN: 0493605584Subjects--Topical Terms:
1017734
Biology, Microbiology.
Investigations into the humoral and cellular mechanisms of alphavirus clearance from neurons in the central nervous system.
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Together, the data presented in this work further our understanding of the mechanisms of virus clearance in the CNS, and establish IFN-γ as an important mediator of non-cytolytic clearance of virus from neurons in the CNS.
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Alphaviruses are neurotropic mosquito-borne viruses that can cause severe encephalitis in humans. Sindbis virus (SV) is an alphavirus that is pathogenic in mice after central nervous system (CNS) inoculation. Virus infection induces a well-characterized immune response which clears infectious virus from the CNS within 7–8 days without inducing clinical illness or paralysis. Previous studies have demonstrated that anti-viral antibody is sufficient for non-cytolytic clearance of SV from neurons. To investigate the mechanism of antibody-mediated clearance, the site of action was studied. It was found that antibody can function distally, and does not need to be taken up into a cell to mediate clearance effects.
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To explore alternative mechanisms of clearance, SV replication and clearance in the brain and spinal cord of antibody deficient mice were examined. Although virus persisted in the brain, infectious virus was cleared in the spinal cord without paralysis in a time course similar to wild type mice. A series of T cell depletion studies established both CD4<super>+</super> and CD8<super> +</super> cells as mediators of clearance. The cytokines interferon (IFN)-γ and tumor necrosis factor (TNF)-α are produced by both T-cell subsets, have been shown to have direct antiviral activity, and are significantly upregulated during SV infection. Infection of severe combined immune deficiency (SCID) mice with recombinant viruses engineered to produce IFN-γ and TNF-α revealed that IFN-γ but not TNF-α is sufficient to clear virus from the spinal cord. The site-specific nature of cytokine-mediated clearance in the CNS did not appear to be due to a differential immune response or virus spread. Analysis of virus clearance from distinct brain regions revealed that virus was cleared from the spinal cord and brainstem, but not the cortex suggesting a neuron cell type-specific response to cytokine-mediated clearance. Staining for the IFN-γRα showed that the receptor was located throughout these regions, although expression was higher in the regions where virus was cleared.
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