Travis Taylor, Ph.D.
- Identification of virus-specific antiviral or proviral molecules by characterizing virus and host protein interactions.
- Mechanisms of virus evasion of innate immunity.
- Regulation of multi-functional viral protein functions by host-mediated post translational modifications.
Currently Dr. Taylor’s research focuses on the arthropod-transmitted members of the Flaviviridae family. Flaviviruses are globally significant human pathogens including dengue virus (DENV), West Nile virus (WNV) and the TBEV serocomplex of viruses. Select members of the TBEV serocomplex includes the highly pathogenic TBEV-Sofjin and Powassan virus (POWV) and require biosafety level (BSL)-4 and 3 facilities respectively. The group also includes the naturally attenuated Langat virus (LGTV), which greatly simplifies studies with TBEV under BSL-2 conditions. Viruses in the TBEV serocomplex span the clinical spectrum for flaviviruses. Symptoms range dramatically from asymptomatic infection to more severe encephalitides and hemorrhagic fevers with mortality rates exceeding 30%. Treatment of infection with these viruses is hindered by the lack of effective antiviral therapies and few available vaccines. The overwhelming morbidity, in addition to the risk of emerging viruses, highlights the need for better treatment options. Fresh insight for new antiviral treatments may come from studies of the classical IFN response. IFN treatment induces the expression of hundreds of genes (interferon stimulated genes or ISGs), many of which are antiviral molecules. Though flaviviruses are highly sensitive to the antiviral effects of IFN, viral antagonism of IFN signal transduction prevents the expression of ISGs in infected cells. Thus, virus suppression of IFN signaling renders IFN ineffective as a medicinal therapy for flavivirus infections. Identifying ISGs with virus-specific antiviral activity may reveal new methods for treating flavivirus infections.
A major accomplishment of Dr. Taylor’s work has been the identification of a previously unnamed mouse-specific tripartite motif (TRIM) protein (now designated TRIM79) that targets the nonstructural 5 protein (NS5) from TBEV to inhibit virus replication. NS5 is the major IFN antagonist for flaviviruses and is an essential component of the virus replication complex and as such is a prime candidate for antiviral drug design. Focus in the lab will characterize the TRIM79-NS5 interaction, and ultimately determine the importance of the antiviral molecule to host protection in a mouse model of TBEV infection. Additionally Dr. Taylor’s lab is using various screening approaches including shRNA libraries and mass spectrometry to identify new virus-host interactions that can be targeted as part of a virus-specific immune therapy. Finally, viral proteins have evolved the capacity to perform many important functions during the virus life cycle. NS5, for instance is necessary for virus replication and immune evasion. Understanding how the virus protein can maintain different functions and protein interactions in distinct cellular regions may again lead to new therapeutic targets. Previous studies by Dr. Taylor have determined that NS5 is modified by the cellular ubiquitation machinery. Understanding the importance of this post-translational modification may provide insight into NS5 regulation and/or cellular mechanisms to interfere with NS5 function.
Dr. Taylor received his Ph.D. degree at the University of Texas Southwestern Medical Center at Dallas under the mentorship of Dr. Wade Bresnahan. He then completed his postdoctoral training at the NIH Rocky Mountain Laboratories where he studied the biosafety level (BSL)-4 tick-borne flaviviruses in the laboratories of Drs. Marshall Bloom and Sonja Best. Dr. Taylor joined the Department of Medical Microbiology and Immunology in August of 2012.
Current Grant Funding:
Lyme Disease Association Pilot Grant. Restriction of tick-borne flaviviruses in the natural host. Jan 2015-Jan 2016.
NIAID K22 Research Scholar Development Award. Role of TRIM79 in innate immunity to tick-borne encephalitis virus. Feb 2013- Feb 2015 (completed).
Novella I, Presloid J, and RT Taylor. 2014. RNA replication errors and the evolution of virus pathogenicity and virulence. Current Opinion in Virology 9: 143-147.
Mehedi M, Hoenen T, Robertson S, Ricklefs S, Dolan M, Taylor T, Falzarano D, Ebihara H, Porcella S, and H Feldmann. 2013. Ebola virus RNA editing depends on the primary editing site sequence and an upstream secondary structure. PLoS Pathogens 9(10): e1003677. doi:10.1371/journal.ppat.1003677.
Baker DG, Woods T, Butchi N, Morgan T, Taylor RT, Sunyakumthorn P, Lubick K, Best S, and K Peterson. 2012. TLR7 suppresses virus replication in neurons, but does not alter viral pathogenesis in a mouse model of Langat virus infection. Journal of General Virology 94: 336-347.
Taylor RT, Lubick KJ, Robertson SJ, Broughton JP, Bloom ME, Bresnahan WA, and SM Best. 2011. TRIM79a, an interferon stimulated gene product, restricts tick-borne encephalitis virus replication by degrading the viral RNA polymerase. Cell Host & Microbe 10: 185-196.
Taylor RT and SM Best. 2011. Assessing the ubiquitination of viral proteins: Lessons from flavivirus NS5. Methods 55: 166-71.
Robertson SJ, Mitzel DN, Taylor RT, Best SM and ME Bloom. 2008. Tick-borne flaviviruses: dissecting host immune responses and virus countermeasures. Immunologic Research 43:172–186.
Taylor RT and WA Bresnahan. 2006. Human Cytomegalovirus IE86 Attenuates Virus and TNFα-induced NFκB-Dependent Gene Expression. Journal of Virology 80(21): 10763-10771.
Taylor RT and WA Bresnahan. 2006. Human Cytomegalovirus Immediate-Early 2 Protein IE86 Blocks Virus-Induced Chemokine Expression. Journal of Virology 80(2): 920-928.
Taylor RT and WA Bresnahan. 2005. Human Cytomegalovirus Immediate-Early 2 Gene Expression Blocks Virus-Induced Beta Interferon Production. Journal of Virology 79(6): 3873–3877.
Zou Y, Bresnahan W, Taylor RT, and P Stastny. 2005. Effect of Human Cytomegalovirus on Expression of MHC Class I-Related Chains A. The Journal of Immunology 174: 3098–3104.