Alex Compton, Ph.D.
HIV DRP Retroviral Replication Laboratory
Building 535, Room 307
Frederick, MD 21702-1201
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 incorporation into the HIV Dynamics and Replication Program 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
Dr. Alex Compton received his Ph.D. in Molecular and Cellular Biology from the University of Washington in 2012. As a doctoral student in the laboratory of Dr. Michael Emerman (Fred Hutchinson Cancer Research Center), he investigated the HIV-1 Vif protein and its target APOBEC3G, revealing lentivirus-driven evolution of host proteins on a million-year time scale. Dr. Compton was the recipient of a Pasteur Foundation Postdoctoral Fellowship and an ANRS (French National Agency on AIDS Research) Grant during his postdoctoral training with Dr. Olivier Schwartz at the Pasteur Institute in Paris, where he made key discoveries on the mechanisms by which the interferon-induced transmembrane (IFITM) proteins restrict HIV-1 infection. These studies provide important insight into the complex ways in which mammalian cells have evolved to counteract viral infections. Because the APOBEC and IFITM proteins restrict the replication of a number of viruses in addition to HIV, this work has broad implications for the understanding of host-pathogen interactions. In 2017, Dr. Compton joined the HIV Dynamics and Replication Program as Head of the Antiviral Immunity and Resistance Section to develop a research program focused on mechanisms of protection mediated by the cell-intrinsic innate immune response, as well as the strategies employed by HIV and emerging viruses to evade or overcome these immune barriers.
Ozog S, Timberlake ND, Hermann K, Garijo O, Haworth KG, Shi G, Glinkerman CM, Schefter LE, D'Souza S, Simpson E, Sghia-Hughes G, Carillo RR, Boger DL, Kiem HP, Slukvin I, Ryu BY, Sorrentino BP, Adair JE, Snyder SA, Compton AA, Torbett BE. Resveratrol trimer enhances gene delivery to hematopoietic stem cells by reducing antiviral restriction at endosomes. Blood. 2019;134(16):1298-1311.
Shi G, Ozog S, Torbett BE, Compton AA. mTOR inhibitors lower an intrinsic barrier to virus infection mediated by IFITM3. Proc Natl Acad Sci U S A. 2018;115(43):E10069-E10078.
Shi G, Schwartz O, Compton AA. More than meets the I: the diverse antiviral and cellular functions of interferon-induced transmembrane proteins. Retrovirology. 2017;14(1):53.
Related Scientific Focus Areas
Genetics and Genomics
Molecular Biology and Biochemistry
This page was last updated on September 11th, 2019