For nearly half a billion years, retroviruses and the animal immune systems they infect have each evolved strategies to outmaneuver the other in a kind of molecular arms race. HIV—which crossed into humans in the early 1900s—has inherited and advanced the strategies of its retrovirus predecessors.
HIV uses the molecular machinery inside the host cell to replicate. Studying interactions between the viral and host proteins reveals mechanisms of infection including viral replication, the host response, and how the virus eludes that response.
The Research Question
In two new studies, amfAR-funded researchers reported on methods used by HIV to impede immune defenses. In one study, Dr. Jonathan Richard of Université de Montréal, Centre de Recherche du CHUM and colleagues investigated how a viral protein targeted multiple cellular defenses at once. In another study, Dr. Judd Hultquist of Northwestern University School of Medicine and colleagues investigated how the virus “hijacked” host proteins involved in an antiviral defense pathway.
HIV virions bud from the cell membrane and then travel to infect a new cell. The host protein BST-2, or tetherin, defends against budding by tethering virions to the cell membrane. In response, HIV uses its viral protein Vpu to prevent BST-2 from tying down the emerging virion.
Vpu also thwarts another host defense: the recognition and killing of infected cells by natural killer (NK) cells. Dr. Richard and colleagues reported that the drug interferon alpha (IFNa) increased the amount of BST-2 in the cell, requiring more Vpu to counteract it. This left less Vpu available to stop NK cells, allowing them to hunt and kill virally infected cells.
Dr. Hultquist and colleagues used an innovative combination approach to investigate how the viral protein Vif hijacks the machinery a cell uses to degrade unwanted proteins, causing it instead to destroy APOBEC3—an important antiviral host cell protein. The researchers noted that better understanding these virus and host interactions could offer new targets for antiviral therapies and vaccines.
These studies each show that viral and host immune system interactions can be manipulated to develop more effective treatments.
Both Drs. Jonathan Richard and Judd Hultquist are funded by amfAR.
Dr. Flores is amfAR’s associate director of research.