Grant: Project Grant

HIV-1 remains a major global health problem, with 38 million people living with the virus worldwide. To date scientists have not developed a successful vaccine to prevent HIV-1 infection. The virus enters human cells using a viral surface glycoprotein termed gp160. HIV-1 gp160 is commonly known for its central role in host attachment and fusion of the viral envelope with the host membrane, thus allowing for the deposition of infectious materials into the host. However, the fusion subunit of HIV-1 gp160 has also been implicated in contributing to disease progression through immune evasion, misdirection, and confrontation. A better understanding of the mechanisms employed by HIV-1 to escape immune responses is key to the development of novel therapeutic approaches. We aim to understand the mechanisms of how HIV-1 modulates the immune system. We will characterize interactions of HIV-1 with the immune system using an integrative approach that combines structural virology, immunology, biochemistry and computation. Our results will identify new fundamental model principles to explain immunosuppression and immunodominance, to better understand the virus-host conflict. The proposed work has the potential to both impact the design of vaccines as well as provide new therapeutic strategies aimed at activating the host immune system against HIV.