Virus-Host Interactions in HIV-1 Pathogenesis and Viral Immune Evasion
Public Deposited- Last Modified
- March 19, 2019
- Creator
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Tsao, Li-Chung
- Affiliation: School of Medicine, Curriculum in Genetics and Molecular Biology
- Abstract
- Human viruses such as the Human Immunodeficiency virus (HIV-1) causes chronic diseases and is a major public health concern. My dissertation focuses on the molecular interactions between the virus and the host, tackling two major topics in HIV-1 research. The first topic focuses on HIV-1 pathogenesis and the factors contributing towards AIDS disease progression. Using genetics and pharmacological approaches, we demonstrated the interaction between the viral envelope and the CCR5 receptor contributes to the killing of uninfected bystander CD4 T cells in vitro and in vivo. This study suggests therapeutic strategies targeting CCR5 may reduce HIV-1 pathogenesis and AIDS disease progression. The second topic focuses on how HIV-1 escapes from restriction factors, a critical part of our innate immune defense against HIV-1. We discovered the TET2 methylcytosine dioxynase is a new HIV-1 restriction factor that binds to HIV-1 cDNA and inhibits viral reverse transcription. The viral accessory protein Vpr hijacks the CRL4VprBP E3 ligase to promote the degradation of TET2 and thereby relieving this restriction. Lastly, we also discovered an alternative role of TET2 in modulating the Type-1 interferon antiviral response in HIV-1 inhibition. We demonstrated TET2 is essential for the interferon-mediated induction of antiviral proteins that targets HIV-1 replication, including MX2 and IFITM3. We report a new restriction factor TET2 that inhibits HIV-1 through various mechanisms, and we elucidated the mechanism how Vpr promotes HIV-1 escape from this immune defense. In summary, my dissertation research unraveled the contributions of different virus-host interactions towards viral pathogenesis and viral immune evasion, which may provide new therapeutic targets for HIV-1 treatments.
- Date of publication
- December 2016
- Keyword
- DOI
- Resource type
- Rights statement
- In Copyright
- Advisor
- Xiong, Yue
- Su, Lishan
- Deshmukh, Mohanish
- Ting, Jenny P.-Y.
- Miao, Edward
- Heise, Mark
- Degree
- Doctor of Philosophy
- Degree granting institution
- University of North Carolina at Chapel Hill Graduate School
- Graduation year
- 2016
- Language
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