Characterizing Host-Virus Interactions in a New HIV Model Organism

点击翻译按钮获取中文摘要

PROJECT SUMMARY HIV remains the most consequential zoonosis of the last century, with 36 million fatalities and another 37 million infected. Even today, almost 2,000 people per day die of HIV/AIDS globally. Medications are reducing the effects of HIV on the human body and transmission of the virus to others. However, forty years into the HIV/AIDS pandemic, there are still no vaccines or cures. One hindrance to the development of HIV vaccines and cures has been the lack of an effective animal model organism. Macaques were thoughtfully developed as an animal model in the 1980s and remain the main HIV model today. However, there are well-known problems with this model, with the most significant problem being that SHIVs can only be made to contain about 30% of the HIV-1 genome (essentially, just Env). Here, we describe a new animal model for HIV infection. The overarching goal of this grant is to design and test physiologically-relevant transmitted/founder (T/F) HIV-1 strains for this new model species. We examine and optimize the ability of these viruses to bind to CCR5 and RanBP2 host factors in the new model species, and study how the virus is evading restriction factors in this species. All newly developed viruses will then be assayed for their sensitivity to neutralization by HIV-1 antibodies. Taken together, we will learn about the molecular underpinnings of HIV host switching, and at the same time the viruses we design in this proposal will become a vital tool for HIV-1 research. This new animal model will serve as an exciting new model system in which to study all aspects of HIV-1 biology and immunity.