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John E. Tavis, Ph.D.

Molecular Microbiology and Immunology


Ph.D. in Molecular Biology, Pennsylvania State University, 1990


Our lab studies Hepatitis B virus (HBV) and Hepatitis C virus (HCV). HBV and HCV are major causes of liver disease, including liver cancer, and together they cause nearly two millions of deaths each year world-wide. HBV is a Hepadnavirus with a DNA genome that replicates by reverse transcription using a virally-encoded reverse transcriptase. HCV is a non-vector borne Flavivirus and has a highly variable RNA genome.

Hepatitis B virus. The key enzyme in HBV replication is its reverse transcriptase. The reverse transcriptase is the main target of anti-HBV nucleoside analog drugs that are incorporated into the viral DNA and block viral replication. They are very good drugs, but they are not quite strong enough to eliminate the infection. Therefore, new drug targets that function by different mechanisms are needed to permit combination drug therapy. To identify such targets, we are studying the reverse transcriptase, using both HBV and the related animal virus, Duck Hepatitis B virus (DHBV).

Our primary focus is on the viral ribonuclease H activity that destroys the viral RNA after it has been copied into DNA. We recently expressed the HBV RNAseH as an active recombinant protein and found that it could be inhibited by antagonists of the HIV RNAseH and integrase enzymes. We also demonstrated for the first time that HBV viral replication could be pharmacologically inhibited using antagonists of the RNAseH. These studies provide proof-of-concept that the HBV RNAseH is an attractive target for antiviral drug development, and we are beginning drug discovery efforts. We also work on the mechanism by which the reverse transcriptase binds to the viral RNA that is the template for viral DNA synthesis. We identified two motifs on the enzyme that directly bind to the RNA and have begun to characterize the enzyme’s complex, two-stage RNA binding mechanism. We are extending these studies with the hope that learning how to disrupt these RNA binding interfaces will lead to a new anti-HBV drug.

Inhibition of the HBV RNAseH by β-Thujaplicionol

Figure 1. Inhibition of the HBV RNAseH by β-Thujaplicionol. An oligonucleotide-directed RNA cleavage assay was conducted using a uniformly-labeled RNA and a complementary DNA oligo (+) or a non-complementary oligo (-) as a control. Cutting the RNA:DNA heteroduplex substrate (S) cleaves the RNA into two products (P1 and P2). Plotting the data reveals that β-Thujaplicinol has an IC50 of ~6 μM against the HBV RNAseH.

Hepatitis C virus. HCV is very genetically variable, with six major genotypes and multiple subtypes. The genetic distance between two HCV isolates of the same subtype is larger than the difference between a typical mouse and human gene. We seek to understand how this viral genetic variation affects viral pathology and the response of HCV to antiviral therapy.

The backbone of HCV therapy is interferon alpha plus ribavirin, but this demanding therapy fails in about half of genotype 1 patients (the major genotype in the USA). We sequenced the HCV genome from 94 patients before therapy, stratified by response to the drugs. Viral genetic variability in patients where the virus was efficiently suppressed was much higher than in patients where suppression was minimal. This implies that the viruses in the patients who responded well were cleared due to the presence of many different variations that independently reduced their ability to counteract the strong interferon response induced by therapy, and that HCV in the poor responders survived because there are only a few ways to optimize activity of the viral proteins (and hence little genetic diversity). We are exploring the possibility that novel genome-wide genetic variation patterns we recently identified may provide a reliable clinical test to predict who will respond to interferon-based therapy, and are extending these concepts to other viruses.

HCV causes life-threatening illnesses such as cirrhosis or liver cancer in only about 25% of chronically-infected patients, but the reasons why some patients become seriously ill while disease in others is relatively mild are not understood. We hypothesized that this may be due to the presence of HCV genetic variants with varying degrees of virulence. We are conducting two studies to test this hypothesis. First, we sequenced 120 HCV genomes from 60 patients who had either rapid or slow progression of disease over a 3.5 year period. In the second study we asked whether there are oncogenic variants of HCV. Here, we sequenced the HCV genomes from 47 patients with or without liver cancer. In both cases the viral genetic analyses are being coupled to functional assays of the variant viral genes to provide biochemical evidence for or against virulence differences among the variants.

Figure 1: Select HCV genes

Figure 1. Select HCV genes in sequences from patients who responded well to therapy (marked) are more diverse than from the patients who responded poorly to therapy. Importantly, each of these genes can counteract the function of interferon alpha in vitro.

Labs and Facilities

Lab team members include Nathan Ponzar, Juan Villa Torrecilla, Tiffany Edwards, John Tavis, Jil Daw, Elena Lomonosova, Qilan Li, and Mikhail Ryzhikov.


Tavis, J.E., and Lomonosova, E. (2018). NVR 3-778 Plus Pegylated Interferon-α Treatment for Chronic Hepatitis B Viral Infections: Could 1+1=3? Gastroenterology. 2018 Feb;154(3):481-482.
Pubmed Abstract Link: 29337155

Long, K.R., Lomonosova, E., Li, Q., Ponzar, N.L. Villa, J.A., Touchette, E., Rapp, S., Liley, R.M., Murelli, R.P., Grigoryan, A., Buller, R.M., Wilson, L., Bial, J., Sagartz, J.E., and Tavis, J.E. (2018). Efficacy of hepatitis B virus ribonuclease H inhibitors, a new class of replication antagonists, in FRG human liver chimeric mice. Antiviral Res. 2018 Jan;149:41-47. PMCID: PMC5743599.
Pubmed Abstract Link: 29129708

Chen, Y., Hu, J., Cai, X., Huang, Y., Zhou, X., Tu, Z., Hu, J., Tavis, J.E., Tang, N., Huang, A., and Hu, Y. (2018). APOBEC3B edits HBV DNA and inhibits HBV replication during reverse transcription. Antiviral Res. 2018 Jan;149:16-25.
Pubmed Abstract Link: 29129707

Hirsch, D.R., Schiavone, D.V., Berkowitz, A.J., Morrison, L.A., Masaoka, T., Wilson, J.A., Lomonosova, E., Zhao, H., Patel, B.S., Dalta, S.H., Hoft, S.G., Majidi, S.J., Pal, R.K., Gallicchio, E., Tang, L., Tavis, J.E., Le Grice, S.F.J., Beutler, J.A., and Murelli, R.P. (2017). Synthesis and biological assessment of 3.7-dihydroxytropolones. Org Biomol Chem. 2017 Dec 19;16(1):62-69. PMCID: PMC5748270.
Pubmed Abstract Link: 29098212

Lomonosova, E., Daw, J., Garimallaprabhakaran, A.K., Agyemang, N.B., Ashani, Y., Murelli, R.P., and Tavis, J.E. (2017). Efficacy and cytotoxicity in cell culture of novel α-hydroxytropolone inhibitors of hepatitis B virus ribonuclease H. Antiviral Res. 2017 Aug;144:164-172. PMCID: PMC5549669.
Pubmed Abstract Link: 28633989

Edwards, T.C., Lomonosova, E., Patel, J.S., Li, Q., Villa, J.A., Gupta, A.K., Morrison, L.A., Bailly, F., Cotelle, P., Giannakopoulou, E., Zoidis, G., and Tavis, J.E. (2017). Inhibition of hepatitis B virus replication by N-hydroxyisoquinolinediones and related polyoxygenated heterocycles. Antiviral Res. 2017 Jul;143:205-217. PMCID: PMC5520537.
Pubmed Abstract Link: 28450058

Donlin, M.J., Zunica, A., Lipnicky, A., Garimallaprabhakaran, A.K., Berkowitz, A.J., Grigoryan, A., Meyers, M.J., Tavis, J.E., and Murelli, R.P. (2017). Troponoids can inhibit growth of the human fungal pathogen Cryptococcus neoformans. Antimicrob. Agents and Chemother. PMCID: PMC5365692.
Pubmed Abstract Link: 28167553

Lomonosova, E., and Tavis, J.E. In vitro enzymatic and cell culture-based assays for measuring activity of HBV RNaseH inhibitors. Chapter 14 in Hepatitis B Virus: Methods and Protocols (H. Guo and A. Cuconati, eds.). Springer, New York, New York.
Pubmed Abstract Link: 27975316

Lomonosova, L., Zlotnick, A., and Tavis, J.E. (2016). Synergistic interactions between Hepatitis B Virus ribonuclease H antagonists and other inhibitors. Antimicrob. Agents and Chemother. PMCID: PMC5328565.
Pubmed Abstract Link: 27956427

Lu, G., Villa, J.A., Donlin, M.J., Edwards, T.C., Cheng, X., Heier, R.F., Meyers, M.J. and Tavis, J.E. (2016). Hepatitis B virus genetic diversity has minimal impact on sensitivity of the viral ribonuclease H to inhibitors. Antiviral Research, 135:24-30. PMCID: PMC5099120.
Pubmed Abstract Link: 27693161

Villa, J.A., Pike, D.P., Patel, K.B., Lomonosova, E., Lu, G., Abdulqader, R., and Tavis, J.E. (2016). Purification and enzymatic characterization of the hepatitis B virus ribonuclease H, a new target for antiviral inhibitors. Antiviral Research, 132:186-195. PMCID: PMC4980287.
Pubmed Abstract Link: 27321664

Luo, X. Huang, Y., Chen, Y., Tu, Z., Hu, J., Tavis, J.E., Huang, A., and Hu, Y. (2016). Association of Hepatitis B Virus Covalently Closed Circular DNA and Human APOBEC3B in Hepatitis B Virus-Related Hepatocellular Carcinoma. PLoS One, 11:e0157708.
Pubmed Abstract Link: 27310677

Ireland, P.J., Tavis, J.E., D’Erasmo, M.P., Hirsch, D.R., Murelli, R.P., Cadiz, M.M., Patel, B.S., Gupta, A.K., Edwards, T.C., Korom, M., Moran, E.A., and Morrison, L.A. (2016). Synthetic a-hydroxytropolones inhibit replication of wild-type and acyclovir-resistant herpes simplex viruses. Antimicrob. Agents and Chemother. 60:2140-2149. PMCID: PMC4808205.
Pubmed Abstract Link: 26787704

Counts, C.J., Ho, P.S., Donlin, M.J., Tavis, J.E., and Chen, C. (2015) A Functional Interplay between Human Immunodeficiency Virus Type 1 Protease Residues 77 and 93 Involved in Differential Regulation of Precursor Autoprocessing and Mature Protease Activity. PLoS One. 2015 Apr 20;10(4):e0123561. PMCID: PMC4404164.
Pubmed Abstract Link: 25893662

Tavis, J.E., and Lomonosova, E. (2015). The hepatitis B virus ribonuclease H as a drug target. Antiviral Res. 2015 Jun;118:132-8. PMCID: PMC4424167.
Pubmed Abstract Link: 25862291

Lu G., Lomonosova E., Cheng X., Moran E.A., Meyers M.J., Le Grice S.F., Thomas C.J., Jiang J.K., Meck C., Hirsch D.R., D'Erasmo M.P., Suyabatmaz D.M., Murelli R.P., Tavis J.E.(2015).
Hydroxylated Tropolones Inhibit Hepatitis B Virus Replication by Blocking the Viral Ribonuclease H Activity.
Antimicrob. Agents and Chemother. 2015 59:1070-7079.
Pubmed Abstract link: 25451058

Tavis, J.E., Wang, H. Tollefson, A.E., Ying, B., Korom, M., Cheng, X. Cao, F., Davis, K.L., Wold, W.S.M, and Morrison, L.A.
Inhibitors of nucleotidyl transferase superfamily enzymes suppress herpes simplex virus replication.
Antimicrobial Agents and Chemotherapy 2014 58:7451-7461.
Pubmed Abstract link: 25267681

Donlin, M.J., Lomonosova, E., Kiss, A., Cheng, X., Cao, F., Curto, T.M., Di Bisceglie, A., and Tavis, J.E.
HCV genome-wide genetic analyses in context of disease progression and hepatocellular carcinoma.
PLoS One 2014 9:e103748.
Pubmed Abstract link: 25079603

Gehring A., Bertoletti, A., and Tavis, J.E. (2014). Host factor-targeted hepatitis B virus therapies. Intervirology. 2014;57(3-4):158-62.
Pubmed Abstract link: 25034483

Chowdhury, A.Y., Tavis J.E., and George, S.L.
Human pegivirus (GB virus C) NS3 protease activity inhibits induction of the type I interferon response and is not inhibited by HCV NS3 protease inhibitors.
Virology 2014 456-457:300-309.
Pubmed Abstract link: 24889249

Cai, C.W., Lomonosova, E., Moran, E.A., Cheng, X. Patel, K.B., Bailly, F., Cotelle, P., Meyers, M.J., and Tavis, J.E.
Hepatitis B virus replication is blocked by a 2-hydroxyisoquinoline-1,3(2H,4H)-dione (HID) inhibitor of the viral ribonuclease H activity.
Antiviral Research 2014 108:48-55.
Pubmed Abstract link: 24858512

Cao, F., Jones, S.A., Li, W., Cheng, X., Hu, Y., Hu, J., and Tavis, J.E.
Sequences in the terminal protein and reverse transcriptase domains of the hepatitis B virus polymerase contribute to RNA binding and encapsidation.
Journal of Viral Hepatitis 2014 21:882-893.
Pubmed Abstract link: 24401091

Jones, S.A., Clark, D.N., Cao, F., Tavis, J.E., and Hu, J.
Comparative analyses of Hepatitis B Virus polymerase sequences required for viral RNA binding, packaging and protein priming.
Journal of Virology 2014 88:1564-1572.
Pubmed Abstract link: 24227865

Tavis, J.E., Gehring, A.J., and Hu, Y. (2013). How further suppression of virus replication could improve current HBV treatment. Expert Rev Anti Infect Ther. 2013 Aug;11(8):755-7. PMCID: PMC4436969.
Pubmed Abstract Link: 23977931

Hu, Y., Cheng, X., Cao, F., Huang, A. and Tavis, J.E.
β-Thujaplicinol Inhibits Hepatitis B Virus Replication by Blocking the Viral Ribonuclease H Activity.
Antiviral Research 2013 99:221-229.
Pubmed Abstract link: 23796982

Tavis, J.E., Cheng, X., Hu, Y., Totten, M., Cao, F., Michailidis, E., Aurora, R., Meyers, M.J., Jacobsen, J., Parniak, M.A., and Sarafianos, S.G.
The hepatitis B virus ribonuclease H is sensitive to inhibitors of the human immunodeficiency virus ribonuclease H and integrase enzymes.
PLos Pathogens; 2013. 9:e1003125.
Pubmed Abstract link:23349632

Schvoerer, E., Moenne-Loccoz, R., Murray, J.M., Velay, A., Turek, M., Fofana, I., Fafi-Kremer, S., Erba, A.C., Habersetzer, F., Foffoel, M., Gut, J.P., Donlin, M.D., Tavis, J.E., Zeisel, M.D., Stoll-Keller, F., and Baumert, T.F.
Hepatitis C virus envelope glycoprotein signatures are associated with treatment failure and modulation of viral entry and neutralization.
J. Infect. Dis.; 2013. 9:e1003125.
Pubmed Abstract link:23335805

Lara, J., Tavis, J.E.,Donlin, M.J., Lee, W., Yuan, H.J., Pearlman, B., Vaughan, G., Forbi, J., Xia, G.L., and Khudyakov, Y.
Coordinated evolution among hepatitis C virus genomic sites is coupled to host factors and resistance to interferon.
In Silico Biology; 2012. 11:213-224.
Pubmed Abstract link:23202423

Terrault, N.A., Dodge, J.L., Murphy, E.L., Tavis, J.E., Kiss, A., Levin, T.R., Gish, R., Busch, M., Reingold, A.L., and Alter, M.J.
Sexual transmission of HCV among monogamous heterosexual couples: The HCV Partners Study.
Hepatology; 2013. 9:e1003125.
Pubmed Abstract link:23175457

George, S.L., Varmaz, D.,Tavis, J.E., and Chowdhury, A..
The GB virus C (GBV-C) NS3 serine protease inhibits HIV-1 replication in a CD4+ T lymphocyte cell line without decreasing HIV receptor expression..
PLoS One; 2011. Jan; 7:e30653.
Pubmed Abstract link:22292009.

Donlin, M.J., Szeto, B., Gohara, D.W., Aurora, R., and Tavis, J.E.
Genome-wide networks of amino acid covariances are common among viruses .
J. Virol.; 2012. Mar; 86:3050-3063.
Pubmed Abstract link:22238298.

Cao, F., and Tavis, J.E.
RNA elements needed for translation of the duck Hepatitis B virus polymerase via ribosomal shunting.
J. Virol.; 2011. May; 85:6463-6352.
Pubmed Abstract link:21507974.

Tavis, J.E., Donlin, M.J., Aurora, R., Fan, X., and Di Bisceglie, A.M. (2011). Prospects for personalizing antiviral therapy for hepatitis C virus with pharmacogenetics. Genome Med. 2011 Feb 8;3(2):8. PMCID: PMC3092093.
Pubmed Abstract Link: 21345258

Wagoner, J., Morishima, C., Graf, T.N., Oberlies, N.H., Teissier, E., Pecheur, E.I., Tavis, J.E., and Polyak S.J.
Differential in vitro effects of intravenous versus oral formulations of silibinin on the HCV life cycle and inflammation.
PLoS One; 2011. Jan; 6:e16464.
Pubmed Abstract link:21297922.

Cao, F., Donlin, M.J., Turner, K., Cheng, X., and Tavis, J.E.
Genetic and biochemical diversity in the HCV NS5B RNA polymerase in the context of interferon α plus ribavirin therapy.
J. Viral Hepat; 2011. May; 18:349-357.
Pubmed Abstract link:20529202

Wagoner, J., Negash, A., Kane, O.J., Martinez, L.E., Nahmias, Y., Bourne, N., Owen, D.M., Grove, J., Brimacombe, C., McKeating, J.A., Pecheur, E.-I., Graf, T.N,., Oberlies, N.H., Lohmann, V., Cao, F., Tavis, J.E., and Polyak, S.J.
Multiple effects of silymarin on the Hepatitis C virus lifecycle.
Hepatology; 2010. Jun; 51:1912-1921.
Pubmed Abstract link:20512985.

Donlin, M.J., Cannon, N.A., Aurora, R., Li, J., Wahed, A.S., Di Bisceglie, A., and Tavis, J.E.
Contribution of genome-wide HCV genetic differences to outcome of interferon-based therapy in Caucasian American and African American patients.
PLoS One; 2010. Feb; 5:e9032.
Pubmed Abstract link:20140258.

Cano-Monreal, G.L., Wylie, K.M., Cao, F., Tavis, J.E., and Morrison, L.M.
Herpes simplex virus 2 UL13 protein kinase disrupts nuclear lamins.
Virology, 2009. Sep; 392:137-147.
Pubmed Abstract link:19640559.

Badtke, M.P., Khan, I., Cao, F., Hu, J., and Tavis, J.E.
An inter-domain RNA binding site on the hepadnaviral polymerase that is essential for reverse transcription.
Virology 2009 Jul 30; 390:130-138.
Pubmed Abstract link:19467554.

Cannon, N.A., Donlin, M.J., Mayes, L.M., Castro, A.L., Di Bisceglie, A.M., and Tavis, J.E.
Evidence for action of ribavirin through the hepatitis C virus RNA polymerase.
J. Viral Hepat. 2009 Aug; 16:595-604.
Pubmed Abstract link:19243495.

Dazert, E., Neumann-Haefelin, C., Bressanelli, S., Fitzmaurice, K., Kort, J., Timm, J., McKiernan, S., Kelleher, D., Gruener N., Tavis, J.E., Rosen, H., Shaw, J., Bowness, P., Blum, H.E., Klenerman P., Bartenschlager, R., and Thimme, R.
Loss of viral fitness and cross-recognition by CD8+ T cells limit HCV escape from a protective HLA-B27-restricted human immune response.
J. Clin. Invest. 2009 Feb; 119:376-386.
Pubmed Abstract link: 19139562.

Aurora, R., Donlin, M.J., Cannon, N.A., and Tavis, J.E. for the Virahep-C Study Group. Genome-wide hepatitis C virus amino acid covariance networks can predict response to antiviral therapy in humans.
J. Clin. Invest. 2009 Jan; 119:225-236.
Pubmed Abstract link: 19104147.

Cao, F., Scougall, C.A., Jilbert, A.R., and Tavis, J.E.
Pre-P is a secreted glycoprotein encoded as an N-terminal extension of the duck hepatitis B virus polymerase gene.
J. Virol. 2009 Jul 20; 83:1368-1378.
Pubmed Abstract link: 19004940.

Tavis, J.E., and Badtke, M.P. (2009). Hepadnaviral Genomic Replication. Chapter 7 in Viral Genomic Replication, M. Gotte, K. Raney, and C.E. Cameron, eds. Springer, New York, New York. In Press. PMCID: In Process.


Oh, T.S. and Rice, C.M.
Predicting response to hepatitis C therapy.
J. Clin Invest. 2009 Jan; 119:5-7.
Pubmed Abstract link: 19104144.



R01 AI122669 (Tavis, P.I.)
12/01/15 – 11/30/20
“Optimization of alpha-hydroxytropolones as novel inhibitors of the HBV RNaseH”
The goal of this project is to produce the first αHT inhibitors designed specifically against the HBV RNaseH and to define their potential to contribute to effective anti-HBV therapy. It may also produce lead compounds for future drug development.

R03 AI123689 (Tavis, P.I.)
03/17/16 – 02/28/19
“Structural studies of the HBV ribonuclease H”
The goal of this project is to identify crystallization conditions for the HBV RNaseH that are suitable for X-ray crystallographic structural studies.

R21 AI124672 (Tavis, P.I.)
01/01/17 – 12/31/18
“Defining approaches for improving HID and HPD compounds as HBV RNaseH antagonists”
The goal of this project is to conduct very early hit-to-lead optimization of HID and HPD inhibitors of the HBV RNaseH in order to define the best strategies for a subsequent large-scale medicinal chemistry campaign.

R44 GM088948 (Zhang, P.I.)
07/01/14 – 06/30/18
“Direct RT-PCR detection of RNA pathogens in crude samples”
The goal of this Phase II SBIR grant is to develop PCR conditions that work well with whole-blood samples.  Dr. Tavis will provide approved BSLII facilities for Dr. Zhang’s studies.  It is an extension of a successful Phase I SBIR project conducted by DNA Polymerase Technology, Inc. in collaboration with Dr. Tavis.

R01 GM105414 (Blackard, P.I.)
05/02/13 – 04/30/18
“Genotypic & phenotypic characterization of the HCV polymerase (NS5B) in HIV”
The major goal of this grant is to determine how HIV-induced sequence changes in HCV affect function of the HCV NS5B RNA polymerase. Dr. Tavis will conduct Aim 3 of this grant, which involves purifying and biochemically evaluating a collection of variant HCV RNA polymerases.


SLU eRS 2-92309 (Tavis, P.I.)
07/01/16 – 06/30/17
Friends of the Saint Louis University Liver Center
“The HBV e RNA stem loop as a novel anti-HBV drug target”
The goal of this seed grant is to measure anti-HBV efficacy of compounds that bind to the HBV e RNA stem loop.

R01 AI104494 (Tavis, P.I.)
12/01/13 – 11/30/16
“A screen for antiviral compounds targeting the Hepatitis B Virus ribonuclease H”
The goal of this project is to adapt our low-throughput assay for HBV ribonuclease H activity to a high-throughput format and to conduct a proof-of-principle screen for inhibitors.

R03 AI109460 (Tavis, P.I.)
03/15/14 – 03/14/16
“Hepatitis B Virus diversity and ribonuclease H inhibitor efficacy”
The goal of this project is to determine the degree to which HBV’s natural genetic variation will affect its sensitivity to newly-discovered inhibitors of the viral ribonuclease H activity.

U01 DK082871 (Di Bisceglie, P.I.; Tavis, project P.I.)
09/01/14 – 08/31/15
“Prospects for HBV ribonuclease H inhibitors as practical antiviral drugs”
The goals of this ancillary study within the Hepatitis B Virus Research Network are to determine if our existing anti-RNaseH compounds and nuclos(t)ide analog inhibitors act synergistically against HBV replication and if RNaseH genes from viral isolates that are relatively resistant to nucleos(t)ide analogs retain full sensitivity to RNaseH inhibitors.  Note: the only αHT covered by this grant is #46, which is not proposed to be studied in the current R01 application.

3-20264 (Tavis, P.I.)
06/01/13 – 05/31/14
Washington University Institute of Clinical and Translational Sciences
“Repurposing HIV integrase drugs as HBV RNAseH inhibitors”
The goal of this grant is to determine whether analogs of the HIV integrase drugs Raltegravir and Elvitegravir can inhibit the HBV RNAseH.

R01 DK080711 (Fan, P.I.)
03/01/08 – 02/28/14
“Hepatitis C Virus Quasispecies in the Resistance to Antiviral Therapy”
The major goal of this project is to evaluate patterns of genetic variation in the full-length HCV quasispecies during antiviral therapy.

R01 CA126807 (Tavis, P.I.)
01/14/08 – 12/31/13
“HCV genetic variation and hepatocellular carcinoma”
The major goal of this project is to determine how natural sequence variation in the full-length HCV genome affects its oncogenic potential through a combination of genetic and functional analyses.

2-30076 (Tavis, P.I.)
09/01/11 – 02/28/13
Saint Louis University President’s Research Fund
“Biochemical characterization of the HBV RNAseH as a novel drug target”
The major goal of this institutional seed grant is to perform a basic biochemical characterization of recombinant Hepatitis B virus RNAseH proteins from divergent HBV genotypes in preparation for drug screening.

R01 DK074515 (Tavis, P.I.)
07/15/07 – 06/30/12
“Role of HCV sequence variation in pathology”
The major goal of this project was to determine how natural sequence variation in the full-length HCV genome affect its virulence in collaboration with the HALT-C clinical study.

R44 GM088948 (Zhang, P.I.; Tavis, co-investigator)
08/01/10 – 01/31/12
“Direct RT-PCR detection of RNA pathogens and mRNA expression in crude samples”
The major goal of this project is to determine whether PCR additives and specialized Taq polymerases produced by DNA Polymerase Technology, Inc. permit robust direct RT-PCR amplification RNAs from serum or plasma.  Dr. Tavis is P.I. of a subcontract from DNA Polymerase Technology to perform the testing of patient samples under approved biosafety conditions.

3-07813 (Tavis, P.I.)
01/01/10 – 02/28/11
Saint Louis University President’s Research Fund
“HCV covariance networks as biomarkers of non-response to therapy”
The goal of this seed grant was to provide preliminary validation in an external patient cohort of the ability of HCV amino acid covariance networks to predict non-response to interferon α- based therapy.

R43 AI84232 (Cao, P.I.)
04/09/09 – 02/28/11
“An HBV polymerase RNA binding assay suitable for inhibitor screening”
The major goal of this project was to identify the form of recombinant HBV reverse transcriptase best suited for use in a screen for therapeutic inhibitors of RNA binding by the enzyme. Dr. Tavis relinquished the role of P.I. on this project to Dr. Cao when the NIAID converted the application from an R41 STTR to an R43 SBIR grant.

R01 AI057573 (Morrison, P.I.)
05/01/04 – 01/30/10
“Functional analysis of HSV2 tegument proteins in mice”
The major goal of this project was to examine the function and contribution to pathogenesis of the HSV2 tegument proteins UL13 and VP22 in cultured cells and in mice.

R21 CA125321 (Tavis, P.I.)
06/07/07 – 05/31/09
“Variation in NTP use by the HCV polymerase and response to therapy”
The major goal of this project was to determine how natural variation in the HCV RNA polymerase affects its use of ribavirin triphosphate.

R01 AI38447 (Tavis, P.I.)
07/01/96 – 04/30/08
“Analysis of the hepadnaviral reverse transcriptase”
The major goal of this project was to obtain a molecular understanding of the hepatitis B virus reverse transcriptase, using the duck hepatitis B virus enzyme as a model. We studied the activity of the enzyme, its structure, and its interaction with cells.

R03 AI059050 (Morrison, P.I.)
03/01/05 – 02/28/08
“Substrate recognition motif of the HSV-2 UL13 kinase”
The major goal of this project was to identify the substrate recognition motif of the HSV-2 UL13 protein kinase to guide subsequent efforts to determine the role of UL13 in viral replication and pathology.

No Project Number (Tavis, P.I.)
09/01/05 – 08/31/07
Friends of the St. Louis University Liver Center
“Mechanism of ribavirin action through the HCV NS5B RNA polymerase”
The goal of this project was to determine if natural variation in the HCV NS5B RNA-dependent RNA polymerase modulates incorporation of the antiviral nucleoside analog ribavirin, hence modulating its effectiveness.

U01 DK60345 (Tavis, P.I.)
07/01/01 – 04/30/07
“Response of HCV to therapy in African Americans”
The major goal of this project was to analyze genetic variation in HCV associated with success or failure of antiviral therapy with pegylated interferon alpha plus ribavirin in African Americans and Caucasian Americans.