Pathogenesis And Immunology Of Animal And Human Retroviruses

动物和人类逆转录病毒的发病机制和免疫学

• 批准号: 7732418
• 负责人: Bruce Chesebro
• 金额: $ 18.69万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7732418
• 关键词: Amino Acid Sequence; Amino Acids; Animals; Area; Brain; Brain Diseases; Dimensions; Genes; Goals; HIV; Human; Immune response; Immunology; Laboratories; Location; Lymphoid Cell; Mouse Strains; Mus; Neuropathogenesis; Pathogenesis; Peptide Sequence Determination; Retroviridae; Retroviridae Infections; Structure; Surface; Virus; base; env Gene Products; research study

For the past several years wwe having been studying brain disease induced by the Fr98 strain of mouse retrovirus. In FY08 our experiments identified the amino acid residues in the envelope of the Fr98 mouse retrovirus which were required for the brain disease induced by this virus. These residues were located in several separate locations in the linear protein sequence. When the envelope preotein structure was viewed in 3-dimensions based on the crystal structure of a closely related mouse retrovirus, these amino acids were located in two distinct groups. These results supported the idea that two separate areas of the surface of the envelope protein cooperatively influence the neuropathogenesis of this retrovirus. In FY08 our group collaborated with the laboratories of Dr Kim Hasenkrug at LPVD and Dr Warner Greene at UCSF to demonstrate that the Rfv-3 gene discovered in 1978 at LPVD was identical to the APOBEC3 gene which is currently under intense study in the HIV field. These results indicated that APOBEC3 appeared to have previously unsuspected effects on the immune response to retroviruses.

在过去的几年里，WWE 一直在研究由小鼠逆转录病毒 Fr98 株引起的脑部疾病。在 2008 财年，我们的实验鉴定了 Fr98 小鼠逆转录病毒包膜中的氨基酸残基，这是该病毒引起的脑部疾病所必需的。这些残基位于线性蛋白质序列中的几个不同位置。当根据密切相关的小鼠逆转录病毒的晶体结构在三维空间观察包膜蛋白前蛋白结构时，这些氨基酸位于两个不同的组中。这些结果支持了这样的观点，即包膜蛋白表面的两个独立区域共同影响这种逆转录病毒的神经发病机制。 2008 财年，我们小组与 LPVD 的 Kim Hasenkrug 博士和 UCSF 的 Warner Greene 博士的实验室合作，证明 1978 年在 LPVD 发现的 Rfv-3 基因与目前正在 HIV 领域进行深入研究的 APOBEC3 基因相同。这些结果表明 APOBEC3 似乎对逆转录病毒的免疫反应具有先前未曾预料到的影响。

项目成果

Human immunodeficiency virus type 1 envelope-mediated neuronal death: uncoupling of viral replication and neurotoxicity.

人类免疫缺陷病毒 1 型包膜介导的神经元死亡：病毒复制和神经毒性的解偶联。

• DOI: 10.1128/jvi.77.12.6899-6912.2003
• 发表时间: 2003
• 期刊: Journal of virology
• 影响因子: 5.4
• 作者: Zhang,Kunyan;Rana,Farazana;Silva,Claudia;Ethier,Julie;Wehrly,Kathy;Chesebro,Bruce;Power,Christopher
• 通讯作者: Power,Christopher

Grand ideas floating freely. Conference on the new prion biology: basic science, diagnosis and therapy.

伟大的思想自由地飘浮。

• DOI: 10.1093/embo-reports/kvf256
• 发表时间: 2002
• 期刊: EMBO reports
• 影响因子: 7.7
• 作者: Chesebro,Bruce