ヒカンセンセイ ウイルス リュウシ オ サンセイスル フル ゲノム プラスミド オ モチイタ DNA ワクチン ノ カイハツ

京都大学0048新制・課程博士博士(人間・環境学)甲第12403号人博第321号新制||人||79(附属図書館)17||D||180(吉田南総合図書館)24239UT51-2006-J395京都大学大学院人間・環境学研究科相関環境学専攻(主査)教授 速水 正憲, 教授 津田 謹輔, 教授 小松 賢志学位規則第4条第1項該当Doctor of Human and Environmental StudiesKyoto UniversityDA

Genetic similarity of circulating and small intestinal virus at the end stage of acute pathogenic simian-human immunodeficiency virus infection.

To understand the pathogenicity of acquired immune deficiency syndrome (AIDS), it is important to clarify where, when and how the virus replicates in the body of infected individuals. To identify the major virus replication site at the end stage of SHIV infection, we investigated the systemic tissues of SHIV-infected monkeys that developed AIDS-like disease. We quantified proviral DNA, and compared the mutation patterns of the viruses in various systemic tissues and in peripheral blood through phylogenetic analysis of the full genome sequence. We found that the amounts of proviral DNA detected in internal tissues were higher than those in peripheral blood mononuclear cells. In the sequence and phylogenetic tree analyses, the mutation patterns of the viruses in each tissue were generally different. However, the mutation pattern of the viruses in the jejunum and mesenteric lymph node were most similar to that of plasma viral RNA among the tissues examined in all three monkeys. In two of the three monkeys, which were euthanized earlier, viruses in the jejunum and mesenteric lymph node occupied the root position of the phylogenetic tree. Furthermore, in these tissues, more than 50% of SHIV-expressing cells were identified as macrophages based on co-expression of CD68. These results suggest that macrophages of the small intestine and/or mesenteric lymph node are the major virus production site at the end stage of SHIV infection of macaques

Small Intestine CD4+ T Cells Are Profoundly Depleted during Acute Simian-Human Immunodeficiency Virus Infection, Regardless of Viral Pathogenicity▿

To analyze the relationship between acute virus-induced injury and the subsequent disease phenotype, we compared the virus replication and CD4+ T-cell profiles for monkeys infected with isogenic highly pathogenic (KS661) and moderately pathogenic (#64) simian-human immunodeficiency viruses (SHIVs). Intrarectal infusion of SHIV-KS661 resulted in rapid, systemic, and massive virus replication, while SHIV-#64 replicated more slowly and reached lower titers. Whereas KS661 systemically depleted CD4+ T cells, #64 caused significant CD4+ T-cell depletion only in the small intestine. We conclude that SHIV, regardless of pathogenicity, can cause injury to the small intestine and leads to CD4+ T-cell depletion in infected animals during acute infection