CMV DISRUPTION OF CONSTITUTIVE MHC CLASS II
CMV DISRUPTION OF CONSTITUTIVE MHC CLASS II
批准号:
6690776
负责人:
William James Waldman
金额:
$25.81万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2001
资助国家:
美国
项目状态:
已结题
起止时间:
2001-01-01 至 2006-12-31
关键词:
MHC class II antigenactinsconfocal scanning microscopycytomegalovirusflow cytometrygene expressiongenetic librarygenetic mappingimmunofluorescence techniqueimmunoprecipitationintracellular transportlatent virus infectionmicrotubulesmolecular assembly /self assemblyplasmidsprotein foldingtransfectionvesicle /vacuolevirus cytopathogenic effectvirus infection mechanismvirus proteinwestern blottings
中文摘要
描述(摘自申请人摘要)人巨细胞病毒
英文摘要
DESCRIPTION (Verbatim from the applicant's abstract) Human cytomegalovirus
(CMV) is a significant viral cause of morbidity and mortality in transplant
recipients. In these patients CMV disease often results from reactivation of
latent and persistent virus. A central mechanism of persistence is the ability
of CMV to escape detection by host T lymphocyte-mediated immuno-surveillance,
which is mediated by both CD8+ T lymphocytes and CD4+ T lymphocytes. In an
analogous fashion to CMV encoding multiple genes which disrupt MHC class I, it
now appears that CMV has developed mechanisms to evade CD4+ T lymphocyte
mediated immuno-surveillance through disruption of MHC class II molecule
expression. Within infected cells, CMV inhibits IFN-g induced MHC class II
expression by mechanisms that disrupt the IFN-g signaling pathway. Recently the
effect of CMV on MHC class II expression has been expanded to include
inhibition of constitutively expressed class II, by its gene US2. Using a
constitutive HLA class II expressing cell line, we have found a major
CMV-mediated decrease in surface class II expression that is independent of US2
or proteasomal degradation. Our Northern, Western and confocal microscopy
studies suggest that the mechanism is a defect in trafficking of mature class
II to the cell surface. Moreover, this mechanism specifically targets class II,
since studies with mutant CMV lacking the genes that alter class I demonstrate
normal to increased class I expression, but decreased class II surface
expression. Based on our preliminary data, we will test the hypothesis that CMV
specifically blocks class II trafficking by altering the intracellular vesicle
trafficking machinery. In Specific Aim I, we will further characterize the
effect of CMV infection on MHC class II expression. The transport and assembly
of MHC class II molecules in infected cells will be examined using
co-immunoprecipitation, Western blot analyses, and confocal microscopy. In
Specific Aim II, the mechanism(s) of the CMV-mediated decrease in constitutive
MHC class II expression will be investigated, specifically examining the role
of CMV-mediated disruption of the actin and microtubule networks in this
inhibition. We will quantify the effect of CMV on the polymerization, cleavage
and integrity of these structures and determine the mechanism(s) CMV uses to
inhibit their ability to traffic class II positive vesicles. In Specific Aim
III, stable transfections of the U373-CIITA line with CMV Towne strain cosmid
clones will be used, in conjunction with a CMV cDNA library, to identify and
isolate the CMV genes responsible for the decrease in constitutive MHC class II
surface expression.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Endothelial-reactive antibodies: a diagnostic test for Susac's syndrome
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批准号:8048660
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项目类别:
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资助金额:$26.69万
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财政年份:2010
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负责人:William James Waldman
-
依托单位:
Endothelial-reactive antibodies: a diagnostic test for Susac's syndrome
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批准号:8133697
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项目类别:
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资助金额:$14.95万
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财政年份:2010
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负责人:William James Waldman
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依托单位:
Antiviral activity of leflunomide against respiratory syncytial virus
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批准号:7908439
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项目类别:
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资助金额:$30.0万
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财政年份:2009
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负责人:William James Waldman
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依托单位:
Antiviral activity of leflunomide against respiratory syncytial virus
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批准号:7679336
-
项目类别:
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资助金额:$30.76万
-
财政年份:2008
-
负责人:William James Waldman
-
依托单位:
ANTIVIRAL ACTIVITY OF THE IMMUNOSUPPRESSANT LEFLUNOMIDE
-
批准号:6708845
-
项目类别:
-
资助金额:$28.32万
-
财政年份:2001
-
负责人:William James Waldman
-
依托单位:
ANTIVIRAL ACTIVITY OF THE IMMUNOSUPPRESSANT LEFLUNOMIDE
-
批准号:6287600
-
项目类别:
-
资助金额:$29.15万
-
财政年份:2001
-
负责人:William James Waldman
-
依托单位:
ANTIVIRAL ACTIVITY OF THE IMMUNOSUPPRESSANT LEFLUNOMIDE
-
批准号:6632026
-
项目类别:
-
资助金额:$28.32万
-
财政年份:2001
-
负责人:William James Waldman
-
依托单位:
ANTIVIRAL ACTIVITY OF THE IMMUNOSUPPRESSANT LEFLUNOMIDE
-
批准号:6510888
-
项目类别:
-
资助金额:$28.07万
-
财政年份:2001
-
负责人:William James Waldman
-
依托单位:
CMV DISRUPTION OF CONSTITUTIVE MHC CLASS II
-
批准号:6626385
-
项目类别:
-
资助金额:$26.26万
-
财政年份:2001
-
负责人:William James Waldman
-
依托单位:
CMV/IMMUNE INTERACTIONS IN TRANSPLANT ARTERIOSCLEROSIS
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批准号:6030747
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项目类别:
-
资助金额:$10.22万
-
财政年份:1996
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负责人:William James Waldman
-
依托单位:
CMV/IMMUNE INTERACTIONS IN TRANSPLANT ARTERIOSCLEROSIS
-
批准号:2234994
-
项目类别:
-
资助金额:$9.92万
-
财政年份:1996
-
负责人:William James Waldman
-
依托单位:
CMV/IMMUNE INTERACTIONS IN TRANSPLANT ARTERIOSCLEROSIS
-
批准号:2445342
-
项目类别:
-
资助金额:$10.01万
-
财政年份:1996
-
负责人:William James Waldman
-
依托单位:
CMV/IMMUNE INTERACTIONS IN TRANSPLANT ARTERIOSCLEROSIS
-
批准号:2735318
-
项目类别:
-
资助金额:$10.01万
-
财政年份:1996
-
负责人:William James Waldman
-
依托单位:
海外基金