Grant: Project Grant

The Human Immunodeficiency Virus-1 (HIV-1) causes the disease of Acquired Immunodeficiency Syndrome (AIDS). There are currently estimated to be 37 million people worldwide living with HIV/AIDS. When HIV-1 infects a person, there are many barriers that the virus must overcome to establish a long-term infection that results in AIDS. However, HIV-1 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 do their job as well to inhibit replication of HIV. However, they are not completely purged from HIV infected cells and there is evidence of their suppressive action in HIV+ individuals. 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 some of the ways in which APOBEC3 proteins can overcome HIV Vif suppression and are conducting research to understand this better so that we can develop new therapies for HIV based on releasing this natural anti-HIV activity of our immune system. We hope that a new therapy based on APOBEC3 activity would have less toxicity associated with life-long use in comparison to current antivirals since current HIV+ people can live 50 years or more after diagnosis, but often suffer significant co-morbidities