A Protein that Blocks Virus Budding

HIV and other enveloped viruses wrap themselves in the cell's external membrane exterior, forming buds. They are then released from cells using membrane-cutting machinery (called the ESCRT pathway) that they "steal" from the cell. This broad dependence upon the ESCRT pathway provides a potential target for blocking the replication of many different viruses. However, cells depend on the ESCRT pathway to; perform critical functions, meaning that ESCRT-blocking strategies can also be toxic for cells. A collaboration between the labs of University of Utah Health researchers Nels Elde, PhD, and Wesley Sundquist, PhD, showed that some mammals contain duplicated and shortened genes for a key ESCRT protein. The resulting "retroCHMP3" proteins block the release of HIV and other enveloped viruses. Remarkably, retroCHMP3 proteins from primates and mice appear to work by delaying ESCRT processes, causing extreme damage to HIV and other viruses but little harm to cells. This discovery creates the possibility of engineering retroCHMP3 mice and testing whether they are broadly protected against enveloped viruses, with the long-term goal of finding new ways to target the ESCRT pathway to counter viral infections.