Sonja M. Best, Ph.D.
Chief, Innate Immunity and Pathogenesis Unit, LV
The innate immune response is rapidly engaged after virus infection and functions to limit virus replication and mobilize adaptive immune responses. Viruses have evolved diverse strategies to suppress this critical host response and facilitate virus dissemination. In part, virus pathogenesis is a function of both the quality of the innate response evoked and the evasion strategies encoded by the invading pathogen. Thus, understanding the mechanisms underpinning immune activation and virus evasion will lead to improved vaccine design and novel therapeutics for treatment of both infectious and inflammatory disease.
Our current research program is shaped by the NIAID programmatic objectives in biodefense and emerging infectious disease research, namely basic research of pathogen biology and host response to develop effective vaccines and immunotherapeutics. We use flaviviruses (particularly members of the tick-borne encephalitis virus [TBEV] complex and West Nile virus [WNV]) as the primary model of infection to uncover novel cellular proteins requisite for antiviral innate immune responses and to identify virus-encoded mechanisms that antagonize these responses. These studies involve research of viruses at BSL2, BSL3 and BSL4. Our three main areas of research are outlined below.
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Dr. Best received her Ph.D. in biochemistry and molecular biology from the Australian National University where she studied the pathogenesis of myxoma virus, a poxvirus. She conducted her postdoctoral research at Rocky Mountain Laboratories (RML) on the complex role of apoptosis in the replication of parvoviruses. She stayed at RML as a Research Fellow and then a Staff Scientist to investigate virus-host interactions involved in flavivirus pathogenesis. It was during this time that she developed her interests in innate immunity and the molecular mechanisms utilized by flaviviruses to evade these critical host responses. In 2009, Dr. Best established an independent laboratory as a tenure-track investigator to expand her studies on interactions between pathogenic viruses and the host immune response. In 2011, Dr. Best was awarded a Presidential Early Career Award for Scientists and Engineers for her work on flavivirus suppression of innate immune responses.
Shelly J. Robertson, Ph.D., Staff ScientistKristin McNally, Ph.D., Molecular BiologistErin C. Foster, Ph.D., Postdoctoral FellowKirk J. Lubick, M.S., MicrobiologistAbhilash Chiramel, Ph.D., Postdoctoral Fellow
(View list in PubMed)
Taylor RT, Lubick KJ, Robertson SJ, Broughton JP, Bloom ME, Bresnahan WA, Best SM. TRIM79α, an interferon-stimulated gene product, restricts tick-borne encephalitis virus replication by degrading the viral RNA polymerase. Cell Host Microbe. 2011 Sep 15;10(3):185-96.
Laurent-Rolle M, Boer EF, Lubick KJ, Wolfinbarger JB, Carmody AB, Rockx B, Liu W, Ashour J, Shupert WL, Holbrook MR, Barrett AD, Mason PW, Bloom ME, García-Sastre A, Khromykh AA, Best SM. The NS5 protein of the virulent West Nile virus NY99 strain is a potent antagonist of type I interferon-mediated JAK-STAT signaling. J Virol. 2010 Apr;84(7):3503-15.
Valmas C, Grosch MN, Schümann M, Olejnik J, Martinez O, Best SM, Krähling V, Basler CF, Mühlberger E. Marburg virus evades interferon responses by a mechanism distinct from ebola virus. PLoS Pathog. 2010 Jan 15;6(1):e1000721.
Best SM. Viral subversion of apoptotic enzymes: escape from death row. Annu Rev Microbiol. 2008;62:171-92.
Park GS, Morris KL, Hallett RG, Bloom ME, Best SM. Identification of residues critical for the interferon antagonist function of Langat virus NS5 reveals a role for the RNA-dependent RNA polymerase domain. J Virol. 2007 Jul;81(13):6936-46.
Best SM, Morris KL, Shannon J, Robertson SJ, Mitzel DN, Park GS, Boer E, Wolfinbarger JB, Bloom ME. (2005). Inhibition of interferon-stimulated JAK-STAT signaling by a tickborne flavivirus and identification of NS5 as an interferon antagonist. J Virol. 2005 Oct;79(20):12828-39.
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Last Updated September 11, 2012
Last Reviewed September 11, 2012