The HIV/AIDS pandemic inflicts approximately 40 million people worldwide. The persistence of HIV in anatomic sanctuary sites such as the brain prevents viral eradication. One of the major natural reservoirs of HIV is macrophages, in particular infected-macrophages infiltrated into the brain also cause neuronal injury. Although the antiretroviral therapy (ART) inhibits viral replication, it does not selectively eliminate vira reservoirs. As such, with the greater life expectancy of infected people, the prevalence of HIV-associated neurological disorder has become a prominent problem. In this proposal, we plan to test a new therapeutic strategy to selectively target viral production and reactivation in the brai in SIV/rhesus macaque model. We have developed a novel HIV/SIV Rev-dependent lentiviral vector carrying therapeutic genes to target HIV/SIV infection. Using this system, we have demonstrated selective killing of HIV-positive cells in cell culture conditions. The proposed research is the first attempt to apply this novel technology to reduce viral persistence in the brain of SIV-infected animals. We plan to test a therapeutic gene, the herpes virus thymidine kinase (HSV1- tk), in rhesus macaques. The Rev-mediated expression of HSV1-tk has the potential to be practically used for the treatment of HIV infection, and may eventually lead to a solution to the disease.
HIV-1 infection causes AIDS that afflicts approximately 40 million people globally. Currently there is no cure for the disease. The proposed research is to test a new therapeutic strategy to treat HIV infection in a SIV/rhesus macaque model. This new treatment targets viral reservoirs in the brain and may lead to a solution to the disease.
|Meltzer, Beatrix; Dabbagh, Deemah; Guo, Jia et al. (2018) Tat controls transcriptional persistence of unintegrated HIV genome in primary human macrophages. Virology 518:241-252|
|Perez, Stefanie; Johnson, Ann-Marie; Xiang, Shi-Hua et al. (2018) Persistence of SIV in the brain of SIV-infected Chinese rhesus macaques with or without antiretroviral therapy. J Neurovirol 24:62-74|
|Yi, Fei; Guo, Jia; Dabbagh, Deemah et al. (2017) Discovery of Novel Small-Molecule Inhibitors of LIM Domain Kinase for Inhibiting HIV-1. J Virol 91:|
|Li, Qin; Li, Wei; Yin, Wen et al. (2017) Single-Particle Tracking of Human Immunodeficiency Virus Type 1 Productive Entry into Human Primary Macrophages. ACS Nano 11:3890-3903|
|Wu, Yuntao (2016) Flow Cytometry-Based Quantification of HIV-Induced T Cell Chemotactic Response. Methods Mol Biol 1407:207-15|
|Ma, Yingxin; He, Zhike; Tan, Tianwei et al. (2016) Real-Time Imaging of Single HIV-1 Disassembly with Multicolor Viral Particles. ACS Nano 10:6273-82|
|Guendel, Irene; Meltzer, Beatrix W; Baer, Alan et al. (2015) BRCA1 functions as a novel transcriptional cofactor in HIV-1 infection. Virol J 12:40|
|Spear, Mark; Wu, Yuntao (2014) Viral exploitation of actin: force-generation and scaffolding functions in viral infection. Virol Sin 29:139-47|
|Spear, Mark; Guo, Jia; Turner, Amy et al. (2014) HIV-1 triggers WAVE2 phosphorylation in primary CD4 T cells and macrophages, mediating Arp2/3-dependent nuclear migration. J Biol Chem 289:6949-59|
|Xu, Guoyan G; Guo, Jia; Wu, Yuntao (2014) Chemokine receptor CCR5 antagonist maraviroc: medicinal chemistry and clinical applications. Curr Top Med Chem 14:1504-14|