Grant: Project Grant - Priority Announcement: Infection and Immunity

The Human Immunodeficiency Virus (HIV) causes the disease of Acquired Immunodeficiency Syndrome (AIDS). There are currently estimated to be 39 million people worldwide living with HIV/AIDS. When HIV infects a person, there are many barriers that the virus must overcome to establish a long-term infection that results in AIDS. However, HIV can overcome these barriers in most people because it produces many different proteins that specifically inhibit the function of proteins in the human immune system. We study a specific interaction between the HIV protein called Vif and the APOBEC3 family of human immune system proteins. The HIV Vif protein causes APOBEC3 proteins to become unstable in cells so that they cannot perform their job to inhibit replication of HIV as well. However, they are not completely purged from HIV infected cells and there is evidence of their suppressive action in people living with HIV. APOBEC3 proteins are able to restrict the replication of HIV by mutating its genetic information so that the virus can no longer produce the proteins that it needs to function. We have recently identified ways in which APOBEC3 proteins can overcome HIV Vif suppression and ways HIV Vif interacts with APOBEC3 proteins that were not previously known. This research aims to understand these interactions at the molecular level so that we can determine the impact of APOBEC3-mediated suppression on HIV at the beginning of HIV infecting cells, which has implications for people living life-long with HIV.