Improving Human Antiviral Immunity, One Cell at a Time

The clinical outcome of viral infection, the difference between survival and death of the host, rests delicately on events occurring at the molecular level of individual cells.  The "cell-intrinsic" arm of innate immunity prevents virus replication in host cells by detecting virus invasion and interfering with the viral life cycle.  As such, cell-intrinsic immune factors, also known as host restriction factors, impose the earliest-acting barriers to invading pathogens.  Research in this field, which relies increasingly on interdisciplinary approaches and bioinformatics, has demonstrated that the survival of single cells equates strongly with survival of the organism, and even of the population (or species) to which it belongs.  Since its inception in 2017, the Compton lab focuses on mechanisms of cell-intrinsic immunity and the strategies employed by HIV and emerging viruses to evade or overcome these immune barriers.

By combining relevant experimental systems in virology with perspectives in cell biology and evolutionary biology, we aim to better understand the factors governing virus entry into cells.  We employ a “cross-species” approach, in which diverse viruses are paired with host cells of diverse species in order to reveal cell-intrinsic barriers that limit virus infection.  Cellular membranes, composed of proteins and lipids, are the first line of defense against infection.  Residents of this critical threshold include cellular transmembrane proteins that remodel membrane vesicles or redirect their trafficking in order to inhibit the viral entry process.  In addition to protecting cells from infection, cellular membrane components also impact the structure and infectivity of nascent virions produced from infected cells.  Overall, cell-intrinsic immunity acting on membranes performs dual antiviral functions by 1) preventing virus infection of individual cells, and 2) limiting the spread of virus between cells.

Current projects in the lab revolve around the following themes:

1. Mechanisms of virus entry into cells and evasion of cell-intrinsic immunity
2. Enhancement of virus delivery for gene editing in human cells and in vivo
3. Signals regulating the intrinsic antiviral state: stress, metabolism, differentiation, and activation