Research Interest: Host intrinsic immunity and poxvirus host range factors
Ph.D., University of Florida College of Medicine
Postdoctoral: University of Florida College of Medicine
The arms race between hosts and pathogens for fitness and ultimately survival is a powerful driving force of evolution. Because of the complicated relationship with the host- dependent yet invasive, at times destructive- viral pathogens can be excellent probing tools for the discovery and understanding of the host defense mechanism at the molecular level. This is the main research interest of the Liu lab.
Poxviruses are large DNA viruses with the life cycle exclusively in the cytoplasm of cells. In addition to genes that are essential to viral replication, poxviruses also encode numerous factors to battle host immune responses, including innate, adaptive, and intrinsic immunity. A subgroup of these viral factors, called host range factors, is of especial interest to the Liu lab. These factors determine the species, tissue, or cell type specificity during infection by poxviruses. Therefore, they can be valuable probing agents for unique antiviral mechanisms in the corresponding cell population or tissue microenvironment. Through targeted knockout of the host range factor in the viral genome, the resulting recombinant virus, often with certain tropism defects, can then be used to screen for the cellular functions and signaling pathways that are directly antagonized by the viral factor. By examining the impact of the loss of these viral factors on the pathogenesis in vivo, we can further obtain insights on the interface of the host-pathogen interaction.
Poxviruses are also valuable tools for therapeutic applications. In addition to being oncolytic agents, poxviruses can be excellent candidates for immuno-virotherapy. Myxoma virus (MYXV), a rabbit specific pathogen, can not only specifically infect cancer cells from other species such as human, mouse, and dog, but is also highly immunogenic for the priming of adaptive immunity. Due to its large size of genome, MYXV can be carefully manipulated to express transgenes to further augment the therapeutic benefit. Finally, MYXV and some immunoregulatory drugs, such as Gemcitabine, can be used in synergy to achieve improved therapeutic effect against tumors. Because of these properties of MYXV, the Liu lab is interested in further developing it as an immunotherapeutic vector for treatment of human diseases such as cancer.
Stress Beyond Translation: Poxviruses and More. Liem J, Liu J. Viruses. 2016 Jun 14;8(6). pii: E169. doi: 10.3390/v8060169. Review. PMID: 27314378
SAMD9 is an innate antiviral host factor with stress response properties that can be antagonized by poxviruses. Liu J, McFadden G. J Virol. 2015 Feb;89(3):1925-31. doi: 10.1128/JVI.02262-14. Epub 2014 Nov 26. PMID: 25428864
Liu J, Rothenburg S, McFadden G. The Poxvirus C7L host range factor superfamily. Curr Opin Virol. 2012 Dec;2(6):764-72. Doi:10.1016/j.coviro.2012.09.12. Epub 2012 Oct25. PMID: 23103013
Liu J, Wennier S, Zhang L, McFadden G. M062 is a host range factor essential for myxoma virus pathogenesis and functions as an antagonist of host SAMD9 in human cells. J Virol. 2011 Apr;85(7):3270-82. PMID: 21248034