PATHOGENIC PROPERTIES OF HTLV-II

HTLV-II 的致病特性

• 批准号: 2106258
• 负责人: WILLIAM W HALL
• 金额: $ 26.23万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-02-01 至 1998-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2106258
• 关键词: HIV infections; Native Americans; Retroviridae disease; T cell receptor; gene rearrangement; genetic mapping; human T cell lymphotropic virus type 2; human subject; intravenous drug abuse; molecular pathology; nucleic acid sequence; polymerase chain reaction; serology /serodiagnosis; suppressor T lymphocyte; virus classification; virus infection mechanism; virus protein

The human T cell leukemia viruses, type 1 (HTLV-I) and type II (HTLV-II) are closely related members of a family of retroviruses which have similar biological properties and a tropism for T lymphocytes. HTLV-1 is associated with both lymphoproliferative and neurological disorders. Although the role of HTLV-II in human disease has yet to be completely understood, recent studies have suggested that infection is also associated with neurological disorders. To better understand the pathogenicity of HTLV-II we have been studying the molecular properties of the virus and the immunological features associated with infection. In preliminary studies we have demonstrated that there are at least two closely related, but distinct molecular subtypes of the virus. In addition, it could be shown, that in contrast to HTLV-I, which has a preferential tropism for CD4+ T lymphocytes, HTLV-II appears to preferentially infect CD8+ T lymphocytes. We intend to expand on these preliminary observations and propose the following studies. First we will carry out extensive nucleotide sequence analysis of selected gene regions of a large number of proviruses. This should allow a more detailed classification of the viruses, and perhaps the identification of additional subtypes. In parallel with this we will initiate studies to determine if the major subtypes may have phenotypic differences. It is also intended to confirm and extend our preliminary observations that the virus has a preferential -tropism for CD8+ T lymphocytes and we will investigate if infection may be associated with clonal expansion of certain CD8 populations. These studies should not only increase our understanding of the pathogenic properties of the virus, but will also provide a strong foundation for studying its role in human disease.

人类 T 细胞白血病病毒 1 型 (HTLV-I) 和 II 型 (HTLV-II) 是逆转录病毒家族密切相关的成员，该家族具有 相似的生物学特性和 T 淋巴细胞的趋向性。 HTLV-1 是 与淋巴增殖性疾病和神经系统疾病有关。 尽管HTLV-II在人类疾病中的作用尚未完全阐明 据了解，最近的研究表明，感染也 与神经系统疾病有关。为了更好地理解 HTLV-II的致病性我们一直在研究其分子特性 病毒的特征以及与感染相关的免疫学特征。 在初步研究中，我们已经证明至少有两个 密切相关但不同的病毒分子亚型。在 此外，可以证明，与 HTLV-I 相比，HTLV-I 具有 HTLV-II 似乎对 CD4+ T 淋巴细胞具有偏好性 优先感染CD8+T淋巴细胞。我们打算在这些方面进行扩展 初步观察并提出以下研究建议。首先我们将 对选定的基因区域进行广泛的核苷酸序列分析 大量的原病毒。这应该允许更详细的 病毒的分类，或许还有病毒的鉴定 额外的亚型。与此同时，我们将启动研究 确定主要亚型是否可能存在表型差异。这是 还旨在确认和扩展我们的初步意见，即 病毒对 CD8+ T 淋巴细胞有偏向性，我们将 研究感染是否可能与克隆扩增有关 某些 CD8 群体。这些研究不仅应该提高我们的 了解病毒的致病特性，但也将 为研究其在人类疾病中的作用奠定了坚实的基础。