CEM15 Role in Fighting Vif

Cells have many defenses against viral infection, including intracellular proteins that interfere with viral replication. Just as mammals have evolved defenses against viruses, viruses have evolved countermeasures to defeat cellular defenses. Vif is a viral gene produced by the HIV virus whose molecular function has remained unclear, but many aspects of its behavior have been revealed. Vif proteins are required for the production of infectious viral particles in many cells, acting to repress an intracellular T cell antiviral defense. Vif interacts with viral RNA and may help package viral genomic RNA to form mature virus. Some Vif is also found packaged in virion particles and multimerization of Vif appears to play a role in its activity.

CEM15 is a cellular protein that provides an intracellular defense against HIV replication in T cells by acting against Vif. Viruses lacking the Vif gene are only able to replicate in cells lacking CEM15 and expressing CEM15 in cells is sufficient to prevent HIV infection. Although this research partially clarifies the function of Vif in HIV replication, many questions remain to be answered. CEM15 may or may not interact directly with Vif to block its function. Vif has been shown to bind to HIV genomic RNA and CEM15 has homology to cytidine deaminases, enzymes that edit RNA. This homology suggests that CEM15 may itself have an enzyme activity that modifies HIV RNA to render virus non-infectious.