Host and viral pathogen interactions.
Ph.D., Johns Hopkins University
In my lab we study how viruses interact with human cells and how such interactions might cause disease. We currently work with two different human viruses: Epstein-Barr virus (EBV), which infects about 95% of the world’s population and causes infectious mononucleosis and some cancers; and Influenza, which causes “the flu” and has in the past caused major epidemics and pandemics. We are interested in how the virus manipulates the host’s cellular proteins and pathways to aid in infection/replication, and how such interactions can be altered to inhibit viral infection or replication.
For Influenza:a genetic screen in Drosophila identified several genetic modifiers of Influenza M2 function. Such modifiers, which are genes involved in the cellular activity of M2 (the viral proton channel), included specific subunits of the cellular V1V0-ATPase, a proton pump which regulates intracellular pH. In mammalian cells, we have used these findings to show that manipulating individual V1V0-ATPase subunits directly affects Influenza viral infection and replication within cells (see the publication “A Drosophila Model for Genetic Analysis of Influenza Viral/Host Interactions”, listed below). In addition, we have found that glucose metabolism indirectly affects influenza viral infection via activity of the V1V0-ATPase pump (see the publication “Glycolytic Control of Vacuolar-Type ATPase Activity: A Mechanism to Regulate Influenza Viral Infection,” listed below).
For EBV:: a genetic screen in Drosophila also identified several genetic modifiers of EBV BRLF1 and BZLF1 function. Of great interest is our finding that Drosophila Tor (Target of rapamycin) is a potent modifier of both BRLF1 and BZLF1 functions. Translation to human cells has shown that the mTOR pathway is a key regulator of EBV lytic replication. This pathway, which promotes mRNA translation, cell growth, autophagy, mitochondrial metabolism, angiogenesis, and adipogenesis, is a potential target for anti-cancer therapy, and perhaps anti-EBV therapy (see the publications “A Study of Epstein-Barr Virus BRLF1 Activity in a Drosophila Model System” and “Inhibition of mTOR inhibits lytic replication of Epstein-Barr virus in a cell-type specific manner”, listed below).
2012-2016 “Inhibition of mTOR Alters Epstein-Barr Virus Lytic Replication”, PI, NIH.
Renewal of “Inhibition of mTOR Alters Epstein-Barr Virus Lytic Replication” is now pending.
Also pending: NIH grant “Organophosphate pesticide exposure leads to alterations in the Epstein-
Barr virus (EBV) life cycle to further promote EBV associated lymphomas.”
Covell, A., Zeng, Z., Wei, J., Adamson A., and LaJeunesse, D. Alternative SiO2 surface energies direct MCDK epithelial behavior. In review.
Adamson, A. and J. Ray. Knockdown of the V1A subunit of the vacuolar V1V0-ATPase proton pump reduces infection by Influenza A virus. In review.
Needham, J. and A. Adamson. BZLF1 Transcript Variants in Epstein-Barr Virus-Positive Epithelial Cell Lines. In review.
Needham, J. and A. Adamson. The transcription factor YY1 mediates Epstein-Barr virus sensitivity to mTOR inhibition. In preparation.
Adamson A. and Siedenburg B. Epstein-Barr virus activation of downstream targets of the mTORC1 and MAPK pathways during lytic replication is dependent upon mTOR activity in a cell-type dependent manner. In preparation.
Adamson, A., Le B., and Siedenburg B. 2014. Inhibition of mTORC1 inhibits lytic replication of Epstein-Barr virus in a cell-type specific manner. Virology Journal 11:110.
Kohio, H. and Adamson, A. 2013. Glycolytic Control of Vacuolar-Type ATPase Activity: A Mechanism to Regulate Influenza Viral Infection. Virology 444: 301-309.
Adamson, A. 2013. Identification of an N-acetylglucosaminyltranferase-IV as a modifier of Epstein-Barr virus BZLF1 activity. Open Journal of Genetics 3(1) 1-5.
Adamson, A., and LaJeunesse D. 2012. A Study of Epstein-Barr Virus BRLF1 Activity in a Drosophila Model System. The Scientific World Journal – Cell Biology Domain 2012:1-9.
Adamson, A., Chohan, K., Kincaid, J., and LaJeunesse D. 2011. A Drosophila Model for Genetic Analysis of Influenza Viral/Host Interactions. Genetics 189: 495-506.
Adamson, A. and Bowling, B. 2006. Functional interactions between the Epstein-Barr virus BZLF1 protein and the promyelocytic leukemia protein. Virus Research 117:244-253.
Adamson, A. 2005. Effects of SUMO-1 upon Epstein-Barr Virus BZLF1 Function and BMRF1 Expression. Biochemical and Biophysical Research Communications 336:22-28.
LaJeunesse, D., K. Brooks, and A. Adamson. 2005. Epstein-Barr virus immediate-early proteins BZLF1 and BRLF1 alter mitochondrial morphology during lytic replication. Biochemical and Biophysical Research Communications 333:438-442.
Adamson, A. 2005. Epstein-Barr virus BZLF1 protein binds to mitotic chromosomes. Journal of Virology 79(12):7899-7904.
Adamson, A., N. Wright, and D. LaJeunesse. 2005. Modeling Early Epstein-Barr Viral Infection in Drosophila melanogaster: The BZLF1 Protein. Genetics 171:1125-1135.
Adamson, A. and S. Kenney. 2001. The Epstein-Barr Virus (EBV) Immediate-Early Protein, BZLF1, is SUMO-1-modified and disrupts PML bodies. Journal of Virology 75:2388-2399.
Adamson, A., D. Darr, E. Holley-Guthrie, R. A. Johnson, A. Mauser, J. Swenson, and S. Kenney. 2000. Epstein-Barr Virus Immediate-Early Proteins BZLF1 and BRLF1 Activate the ATF2 Transcription Factor by Increasing the Levels of Phosphorylated p38 and c-Jun N-Terminal Kinases. Journal of Virology 74:1224-1233.
Adamson, A. and S. Kenney. 1999. The Epstein-Barr Virus BZLF1 Protein Interacts Physically and Functionally with the Histone Acetylase CREB-Binding Protein. Journal of Virology 73:6551-6558.
Adamson, A. and S. Kenney. 1998. Rescue of the Epstein-Barr Virus BZLF1 Mutant, Z(S186A), Early Gene Activation Defect by the BRLF1 Gene Product. Virology 251:187-197.
Adamson, A. and A. Shearn. 1996. Molecular Genetic Analysis of Drosophila ash2, a Member of the Trithorax Group that is Required for Imaginal Disc Pattern Formation. Genetics 144:621-633.
Principles of Biology I (BIO 111)
Cell Biology (BIO 355)
Cell Biology Lab (BIO 356)
Undergraduate Research (BIO 499)
Genes & Signals (BIO 540)
Virology (BIO 583)
Molecular Biological Approaches in Research (BIO 596)
Seminar in Molecular Cell Biology (BIO 609)