Grant: Operating Grant - PA: HIV/AIDS Research Initiative - Biomedical/Clinical Stream

The human immunodeficiency virus (HIV), the causative agent of acquired immunodeficiency syndrome (AIDS), currently infects 33 million people worldwide, 58 000 of which are Canadian. Presently, HIV treatments have made the disease one that is chronic, but manageable, for people who have access to proper medical care. However, the current therapy has significant long term side effects in patients, such as lipid abnormalities and cardiovascular risks. An alternative route for developing HIV therapeutics is to take advantage of human enzymes, naturally present in the immune cells that HIV infects, which have the the ability to restrict HIV replication. These 'host restriction factors' can block the HIV lifecycle at specific steps, but are often thwarted by HIV accessory proteins designed to overcome these barriers. My laboratory's research focuses on the APOBEC3 family of human enzymes that can restrict HIV replication by causing chemical modifications in the HIV genetic material (DNA), which makes the virus non-functional. However, APOBEC3 enzymes can only act in the absence of the HIV virus infectivity factor (Vif) protein, which inhibits APOBEC3 enzymes by a number of mechanisms. If we can enable APOBEC3 enzymes to work better for humans, by designing molecules the block Vif from doing its job, it is possible that the human immune system will be able to manage HIV infection. To this end, my research takes a fine-tuned look at the interactions between Vif and APOBEC3 enzymes by purifying the relevant components from cells and conducting experiments in a test tube. There are many gaps in our understanding of these molecular battles that human APOBEC3 enzymes and HIV Vif wage against each other. Understanding this relationship is the first step for designing APOBEC3-based therapies.