Assistant Professor of Immunology and Molecular MedicineLab Homepage: https://www.theohainlelab.com
We study how cells are protected from infection by viral pathogens. Viruses and the hosts they infect are locked in an evolutionary arms race in which an array of directly-acting intracellular host defenses are antagonized and evaded by viral pathogens. We use functional genomics approaches and molecular virology to understand how key molecular interactions mediate the outcomes of virus infection inside a cell. We primarily study this in the context of HIV and related primate lentiviruses, an animal-to-human viral species transmission with major impacts on human health. We hope to uncover and understand the mechanisms through which viruses and their hosts fight these battles across evolutionary time.
Discovery of key cellular restrictions to HIV infection. Through an HIV-specific CRISPR KO screening approach we created, we are able to uncover blocks to infection. Through HIV-CRISPR screening we continue to uncover new antiviral phenotypes inside cells. Further, we study the molecular mechanisms of action of these antiviral strategies, their role across evolution in defining species barriers to viral infection and the mechanisms by which viruses evade and antagonize these defenses.
HIV capsid as a target of cellular antiviral defense. After fusing at the cell surface the core of HIV must transit through the cytoplasm to the nucleus in order to integrate a DNA copy of its genome into host cell chromosomes. This process is orchestrated by a single HIV protein, the capsid, that must engage with host cell factors to facilitate infection while also evading host antiviral proteins that have evolved specifically to target invading viruses. We recently identified a new component, TRIM34, of an antiviral restriction mechanism that acts to recognize and inhibit HIV cores. We are interested in understanding the mechanisms by which TRIM genes function to inhibit retroviruses, under what conditions viruses are sensitive to this block and how the evolution of TRIM proteins in primates contributes to the blocks to cross-species transmission of retroviruses.
Viral functional genomics. In addition to studying contemporary and retrospective host-virus protein interactions we are interested in further developing tools to prospectively define the molecular rules that dictate the outcomes of these interactions. Our lab aims to develop massively-parallel, high-throughput sequencing approaches as tools for identifying and understanding both host and viral proteins engaged in these arms races. We are pursuing new directions in virus CRISPR screening methods in addition to developing other functional genomics approaches to study host/virus biology.
Twentyman J, Khalifeh A, Felton AL, Emerman M, Ohainle M. Primate TRIM34 is a broadly-acting, TRIM5-dependent lentiviral restriction factor. Retrovirology. 2023 Aug 22;20(1):15. doi: 10.1186/s12977-023-00629-4. PMID: 37608289; PMCID: PMC10464172.
Montoya VR, Ready TM, Felton A, Fine SR, OhAinle M, Emerman M. A Virus-Packageable CRISPR System Identifies Host Dependency Factors Co-Opted by Multiple HIV-1 Strains. mBio. 2023 Feb 28;14(1):e0000923. doi: 10.1128/mbio.00009-23. Epub 2023 Feb 6. PMID: 36744886; PMCID: PMC9973025.
Hsieh E, Janssens DH, Paddison PJ, Browne EP, Henikoff S, OhAinle M, Emerman M. A modular CRISPR screen identifies individual and combination pathways contributing to HIV-1 latency. PLoS Pathog. 2023 Jan 27;19(1):e1011101. doi: 10.1371/journal.ppat.1011101. PMID: 36706161; PMCID: PMC9907829.
Mac Kain A, Maarifi G, Aicher SM, Arhel N, Baidaliuk A, Munier S, Donati F, Vallet T, Tran QD, Hardy A, Chazal M, Porrot F, OhAinle M, Carlson-Stevermer J, Oki J, Holden K, Zimmer G, Simon-Lorière E, Bruel T, Schwartz O, van der Werf S, Jouvenet N, Nisole S, Vignuzzi M, Roesch F. Identification of DAXX as a restriction factor of SARS-CoV-2 through a CRISPR/Cas9 screen. Nat Commun. 2022 May 4;13(1):2442. doi: 10.1038/s41467-022-30134-9. PMID: 35508460; PMCID: PMC9068693.
Ohainle M., Malik H. (2021) A balancing act between primate lentiviruses and their receptor. PNAS 2021 May 18:118(20):e2104741118. doi: 10.1073/pnas.2104741118. PMID:33879567.
Ohainle M.*, Kim K., Keceli S., Felton A., Luban J., Campbell E., Emerman M.* (2020) TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. PLOS Pathogens 16(4): e1008507 PMID: 32282853. *equal contribution
Roesch, F. and Ohainle, M. (2020) HIV-CRISPR: A CRISPR/Cas9 Screening Method to Identify Genes Affecting HIV Replication. Bio-protocol 10(9):e3614. DOI: 10.21769/BioProtoc.3614. PMID: 33659577.
Sharma A., McLaughlin R.N. Jr, Basom R., Kikawa C., OhAinle M., et al. (2019) Macaque interferon-induced transmembrane proteins limit replication of SHIV strains in an Envelope-dependent manner. PLOS Pathogens 15(7): e1007925. PMID: 31260493.
Ohainle M.*, Helms L., Vermeire J., Roesch F., Humes D., Basom R., Delrow J., Overbaugh J., Emerman M* (2018) A Virus-Packageable CRISPR Screen Identifies Host Factors Mediating Interferon Inhibition of HIV. eLife 7:e39823. PMID: 30520725. *equal contribution
Roesch F., Ohainle M., Emerman M. A CRISPR screen for factors regulating SAMHD1 degradation identifies IFITMs as potent inhibitors of lentiviral particle delivery. Retrovirology 2018 Mar 20;15(1):26. DOI: 10.1186/s12977-018-0409-2. PMID: 29554922.
Last Updated 2023-09-11