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
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 received an NSF Graduate Research Fellowship and characterized the coevolution of primate lentiviruses with their hosts. Later, Dr. Compton was the recipient of a competitive postdoctoral fellowship from the Louis Pasteur Foundation to support his work at Institut Pasteur in Paris, France. In the lab of Dr. Olivier Schwartz, he provided important insight into the complex ways in which mammalian cells have evolved to block virus entry into cells. In 2017, Dr. Compton joined the HIV Dynamics and Replication Program as Head of the Antiviral Immunity and Resistance Section. His recent awards include a Collaborative Project Award from the National Interagency Confederation for Biomedical Research (2018) and an NIH Intramural Targeted Anti-COVID-19 Program Award (2020). He is currently on the Editorial Board of Viruses, Frontiers in Virology, and Review Commons and was appointed as Guest Editor for the Journal of Molecular Biology Special Issue on "Antiviral Innate Immunity." Dr. Compton currently serves as an Adjunct Instructor in the Department of Biology at Hood College, as a member of the COVID-19 Scientific Interest Group Steering Committee, and as a CCR Tenure Track Investigator Representative.
- Majdoul S, Compton AA. Lessons in self-defence: inhibition of virus entry by intrinsic immunity. Nat Rev Immunol. 2021.
- Shi G, Kenney AD, Kudryashova E, Zani A, Zhang L, Lai KK, Hall-Stoodley L, Robinson RT, Kudryashov DS, Compton AA, Yount JS. Opposing activities of IFITM proteins in SARS-CoV-2 infection. EMBO J. 2021;40(3):e106501.
- Rahman K, Coomer CA, Majdoul S, Ding SY, Padilla-Parra S, Compton AA. Homology-guided identification of a conserved motif linking the antiviral functions of IFITM3 to its oligomeric state. Elife. 2020;9.
- Ahi YS, Yimer D, Shi G, Majdoul S, Rahman K, Rein A, Compton AA. IFITM3 Reduces Retroviral Envelope Abundance and Function and Is Counteracted by glycoGag. mBio. 2020;11(1).
- 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.
Related Scientific Focus Areas
Genetics and Genomics
Microbiology and Infectious Diseases
This page was last updated on Thursday, August 31, 2023