2004 Fiscal Year Final Research Report Summary
Comparison between histopathological changes and infectious virus productive organs of acute pathogenic and non-pathogenic SHIV infected monkeys-The detection of HIV-1 productive organs.
| Project/Area Number |
13308049
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Laboratory animal science
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| Research Institution | Kyoto University |
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Principal Investigator |
IBUKI Kentaro Kyoto University, Institute for Virus Research, Assistant Professor, ウイルス研究所, 助手 (00273524)
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| Co-Investigator(Kenkyū-buntansha) |
HAYAMI Masanori Kyoto University, Institute for Virus Research, Professor, ウイルス研究所, 教授 (40072946)
MIURA Tomoyuki Kyoto University, Institute for Virus Research, Associate professor, ウイルス研究所, 助教授 (40202337)
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| Project Period (FY) |
2001 – 2004
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| Keywords | SHIV / pathogenicity / acute phase / mucosal infection / tissue distribution of virus producing cells |
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| Research Abstract |
To clarify the early pathological events in SHIV-infected organs, we examined rhesus macaques infected with an acute pathogenic SHIV (SHIV89.6P) or a nonpathogenic SHIV (NM-3rN) by serial necropsies. In the SHIV89.6P-infected monkeys, peripheral blood CD4+ T cells were depleted within 14 days post inoculation (dpi). By the end of second week, plasma viral RNA loads reached their peak levels. Acute thymic involution in the medulla began within 14 dpi. Subsequently, the continuous progression of thymic involution resulted in severe atrophy at 28dpi. Cells that were strongly positive for the virus were identified in the thymic medulla In contrast, NM-3rN-infected monkeys did not show any significant change of CD4+ T cell counts and the peak of their plasma virus load was delayed and lower than that of SHIV89.6P-infected monkeys. NM-3rN-infected monkeys showed no signs of thymic dysinvolution These differences dearly reflect the difference in the virulence of these SHIVs.
A better understan
… More
ding of early events of HIV infection through the mucosal surface, being a major route of HIV infection, is important for developing effective methods for controlling virus infection and replication. In next study, we characterized early phase in rhesus macaques intrarectally inoculated with a acute pathogenic SHIV(C2/1) or a less pathogenic SHIV(cl64). Intrarectal infection of C2/1 in rhesus monkeys occurred not only CD4+T cell exhaustion in peripheral blood by 13dpi but also in the intestinal tracts, the percentage of CD4+ T cell did not change until 13 dpi but at 27 dpi, it suddenly declined. In particular,CD4+CD8+ double-positive(DP) T cells were depleted earlier than CD4 single positive(SP) T cells observed in jejunum. Kinetics of plasma viral RNA loads and the decrease of CD4+ T cell in PBMC of the cl64-infected monkeys were almost the same as that seen in C2/1-infected monkeys. In C2/1-infected monkeys, the virus quickly spread to the intestinal tracts and tymphoid tissues by 3dpi, but then the virus replication occurred far more abundantly in the lymphoid tissues than in the intestinal tracts. In cl64-infected monkeys, the virus replication was delayed and occurred in intestinal tracts at first and then switched in from mesenteric lymph nodes to thymus.
In the intestinal tract of cl64-infected monkeys, DP T cell did not decrease in advance of SP T cell, and DP T cells remained at least till 27 dpi. In a small intestine, SP T cells were depleted at 27 dpi, while those in large intestine did not decrease so much.
The mechanisms of the cell damage in intestinal tracts differ between these SHTVs, and the change in the immune cell populations in intestinal tracts in early phase of virus infection influences subsequent viral pathogenesis Less
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Research Products
(12 results)
