Animal Models for HIV-1 Replication and Pathogenesis

HIV-1 复制和发病机制的动物模型

• 批准号: 8763116
• 负责人: vineet n kewalramani
• 金额: $ 12.96万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 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/8763116
• 关键词: Animal Model; Animals; Basic Science; Cells; Collaborations; Cytoplasm; Development; Drug or chemical Tissue Distribution; Drug resistance; Evolution; Family suidae; Generations; Genetic; HIV Drug Resistance Program; HIV Infections; HIV-1; Immune response; Infection; Macaca; Modeling; Modification; Pathogenesis; Postdoctoral Fellow; Recruitment Activity; Reporting; Serial Passage; Site Visit; Tail; Treatment Efficacy; Virus; Work; antiretroviral therapy; in vivo; response

In collaboration with the groups of Drs. Paul Bieniasz, Theodora Hatziioannou, and Jeff Lifson, we have developed a simian-tropic HIV-1 (stHIV-1) that is approximately 90% HIV-1 in genetic origin and replicates in pig-tailed macaques. The first-generation X4-tropic stHIV-1 is capable of persistent, low-level replication in vivo but with no resultant pathogenesis. In more recent work, R5-tropic versions of stHIV-1 show a similar persistent, albeit not robust, level of replication in infected animals. There is an ongoing collaborative effort to enhance replication of R5-tropic stHIV-1 through further genetic modification as well as in vivo animal passaging of the virus. In addition, in relation to our basic science studies, we are examining whether HIV-1 CA, in macaque cells, triggers innate immune responses due to recognition or uncoating of the PIC in the cytoplasm. We have recently recruited a new postdoctoral fellow to aid in our stHIV-1 related studies. Our current aims in this work include: 1)In vivo, serial passage of R5-tropic stHIV-1 2)Characterization of R5-tropic stHIV-1 tissue distribution and pathogenesis 3)Characterization of innate immune responses in macaque cells in response to HIV-1 CA in stHIV-1 during infection. [Corresponds to KewalRamani Project 3 in the October 2011 site visit report of the HIV Drug Resistance Program]

与Drs团体合作。 Paul Bieniasz，Theodora Hatziioannou和Jeff Lifson，我们开发了一个拟南芥的HIV-1（STHIV-1），遗传起源约为90％HIV-1，并在猪尾猕猴中复制。第一代X4-Tropic STHIV-1能够在体内持久，低水平的复制，但没有导致发病机理。在最近的工作中，STHIV-1的R5循环版本表现出类似的持久性，尽管不稳定，但在感染动物中的复制水平不强。通过进一步的遗传修饰以及该病毒的体内动物传播，正在进行的协作努力，以增强R5-热带STHIV-1的复制。此外，与我们的基础科学研究有关，我们正在研究HIV-1 CA在猕猴细胞中是否会触发因识别或在细胞质中的PIC涂抹而引起的先天免疫反应。我们最近招募了一位新的博士后研究员，以协助我们的STHIV-1相关研究。我们目前在这项工作中的目的包括：1）体内，R5-纤维化STHIV-1的串行通过，R5-纤维化STHIV-1组织分布和发病机理的表征3）在感染过程中响应STHIV-1中HIV-1 CA的猕猴细胞中先天免疫反应的表征。 [在2011年10月的艾滋病毒耐药性计划的现场访问报告中，对应于Kewalramani项目3]