The Bukreyev Lab

lab

Our Lab focuses on investigation of the mechanisms of the high pathogenicity of filoviruses Ebola and Marburg and development of vaccines, antibody treatments and small molecule treatments against these viruses. Our research includes the following specific topics:

  • Investigation of mechanisms of "immune paralysis" caused by filoviruses.
  • Characterization of antibody responses to filovirus infections in humans.
  • Development of therapeutic human monoclonal antibody treatments for filoviruses.
  • Development of mucosal respiratory tract vaccines against filoviruses based on human and non-human paramyxovirus vectors.
  • Development of therapeutics targeting filoviral replication and interferon-antagonist functions.
  • Comparative immunology of bats as a reservoir of filoviruses.
  • Experimental evolution of filoviruses in bats.

To get insight into these scientific topics, we are using molecular tools, including reverse genetics (i.e. development of genetically modified filoviruses from the DNA-copies of their genomes and use of mini-genomes), immunological tools such as multi-parameter flow cytometry, and human immune cells and animal models. Our research includes experiments in a BSL-2 labs and in BSL-4 labs of the Galveston National Laboratory. Our research is supported by grants from NIH and DoD.

Our collaborators include Dr. James Crowe, Jr. (Vanderbilt University), Dr. Chris Basler (Mount Sinai), Dr. Sergei Nekhai (Howard University), Dr. Thomas Geisbert (UTMB), Dr. Siba Samal (University of Maryland) and Dr. Raul Andino (UCSF).

Lab members

Dr. Alex Bukreyev

alexander.bukreyev@utmb.edu

Dr. Kai Huang

kahuang@UTMB.EDU

Dr. Mathieu Iampietro

maiampie@UTMB.EDU

Dr. Philipp Ilinykh

pailinyk@UTMB.EDU

Dr. Brian Kimble

jbkimble@UTMB.EDU

Dr. Michelle Meyer

mnmeyer@utmb.edu

Ms. Colette Peitzsch (lab manager)

capietzs@utmb.edu

Dr. Palaniappan Ramanathan

paramana@UTMB.EDU

Dr. Abhi Prasad

abnprasa@UTMB.EDU

Mr. Adam Ronk

ajronk@UTMB.EDU

Dr. Rodrigo Santos

roimarqu@UTMB.EDU

Dr. Bersabeh Tigabu

betigabu@UTMB.EDU

Dr. Patrick Younan

payounan@UTMB.EDU

Administrative assistant

Ms. Dora Salinas

dasalina@UTMB.EDU

Ebola VP35

Ebola interferon-inhibiting domain (IID)

Selected publications from the lab:

N. M. Lubaki, P. Ilinykh, C. Pietzsch, B. Tigabu, A. N. Freiberg, R. A. Koup, and A. Bukreyev (2013). The lack of maturation of Ebola virus-infected dendritic cells results from the cooperative effect of at least two viral domains. J. Virol. 87(13):7471-7485. The article was chosen for UTMB press release on 05/02/13.

A. A. Bukreyev, K. Chandran, O. Dolnik, J. M. Dye, H. Ebihara, E. M. Leroy, E. Muhlberger, S. V. Netesov, J. L. Patterson, J. T. Paweska, E. O. Saphire, S. J. Smither, A. Takada, J. S. Towner, V. E. Volchkov, T. K. Warren, and J. H. Kuhn (2014). Discussions and decisions of the 2012-2014 International Committee on taxonomy of viruses (ICTV) Filoviridae Study Group, January 2012-June 2013. Arch. Virol. 159(4):821-30.

J. H. Kuhn, Y. Bao, S. Bavari, S. Becker, S. Bradfute, K. Brauburger, J. R. Brister, and A. A. Bukreyev et al. (2014). Virus nomenclature below the species level: A standardized nomenclature for filovirus strains and variants rescued from cDNA. Arch. Virol. 159(5):1229-37.

B. Tigabu, L. Rasmussen, E. L. White, N. Tower, M. Saeed, A. Bukreyev, B. Rockx, J. LeDuc, and J. W. Noah. (2014) A BSL-4 high throughput screen identifies sulfonamide inhibitors of Nipah virus. Assay Drug Dev. Technol. 12(3):155-61

P. A. Ilinykh, B. Tigabu, A. Ivanov, T. Ammosova, Y. Obukhov, T. Garron, N. Kumari, D. Kovalskyy, M. O. Platonov, V. S. Naumchik, A. N. Freiberg, S. Nekhai, and A. Bukreyev (2014). Role of protein phosphatase 1 in dephosphorylation of Ebola virus VP30 and its targeting for the inhibition of viral transcription. J Biol. Chem. 289(33): 22723-38.

J. H. Kuhn, K. Andersen, Y. Bao, S. Bavari, S. Becker, R. S. Bennett, N. G. Bergman, O. Blinkova, S. Bradfute, J. R. Brister, A. Bukreyev, et al. (2014) Filovirus RefSeq entries: decision on filovirus type variants, type sequences, and names. Viruses 6(9):3663-82.

A. I. Flyak, P. A. Ilinykh, C. D. Murin, T. Garron, X. Shen, M. L. Fusco, T. Hashiguchi, Z. A. Bornholdt, J. C. Slaughter, G. Sapparapu, T. G. Ksiazek, A. B. Ward, E. O. Saphire, A. Bukreyev*, and J. E. Crowe, Jr.* (2015) Mechanism of human antibody-mediated neutralization of Marburg virus. Cell 160(5): 893-903. The article was chosen for UTMB and the Vanderbilt University press releases on 5/26/2015. *Co-senior authors.

L. Rasmussen, B. Tigabu, E. L. White, R. Bostwick, N. Tower, A. Bukreyev, B. Rockx, and J. W. Noah. (2015) Adapting High-Throughput Screening Methods and Assays for Biocontainment Laboratories. Assay and Drug Development Technologies. 13(1) 44-54.

P. Ilinykh, M. Lubaki, S. Widen, L. A. Renn, T. C. Theisen, N. R. Rabin, T. Wood, and A. Bukreyev (2015) Different temporal effects of Ebola virus VP35 and VP24 on global gene expression in human dendritic cells. J. Virol. 90(15):7567-83.

M. Meyer, T. Garron, N. M. Lubaki, C. E. Mire, K. A. Fenton, C. Klages, G. G. Olinger, T. W. Geisbert, P. L. Collins, and A. Bukreyev (2015) Aerosolized Ebola vaccine protects primates and elicits lung-resident T-cell responses. J. Clin. Invest. 125(8): 3241-55. The article was chosen for UTMB press release and NIH press release on 7/13/2015.

M. Edwards, C. Pietzsch, T. Thibaut; M. Shaw, A. Bukreyev, and C. Basler. (2015) High-throughput minigenome system for identifying small molecule inhibitors of Ebola virus replication. ACS Infectious Diseases 1(8): 380-387.

A. I. Flyak, X. Shen, C. D. Murin, H. L. Turner, M. L. Fusco, R. Lampley, N. Kose, P. A. Ilinykh, N. Kuzmina, A. Branchizio, H. King, L. Brown, C. Bryan, E. Davidson, B. J. Doranz, J. C. Slaughter, G. Sapparapu, C. Klages, T. G. Ksiazek, E. O. Saphire, A. B. Ward, A. Bukreyev,* and J. E. Crowe, Jr.* (2016) Cross-reactive and potent neutralizing antibody responses in human survivors of natural Ebolavirus infection. Cell 164(3): 392-405. The article was chosen for UTMB and the Vanderbilt University press releases on 1/21/2016, and was highlighted in Nature 529, 440. *Co-corresponding authors.

P. A. Ilinykh, X. Shen, A. I. Flyak, N. Kuzmina, T. G. Ksiazek, J. E. Crowe, Jr., and A. Bukreyev (2016) Chimeric filoviruses for identification and characterization of monoclonal antibodies. J. Virol. 90(8): 3890-901.

C. L. Afonso, G. K. Amarasinghe, K. Banyai, Y. Bao, C. F. Basler, S. Bavari, N. Bejerman, K. R. Blasdell, F. X. Briand, T. Briese, A. Bukreyev, et al. (2016). Taxonomy of the order Mononegavirales: update 2016. Arch. Virol. 161(8):2351-60.

A. Rialdi, L. Campisi, N. Zhao, A. C. Lagda, C. Pietzsch, J. S. Ho, L. Martinez-Gil, R. Fenouil, X. Chen, M. Edwards, G. Metreveli, S. Jordan, Z. Peralta, C. Muniz-Fontela, N. Bouvier, M. Merad, J. Jin, M. Weirauch, S. Heinz, C. Benner, H. van Bakel, C. Basler, A. Garcia-Sastre, A. Bukreyev, and I. Marazzi. (2016) Topoisomerase 1 inhibition suppresses inflammatory genes and protects from death by inflammation. Science. 352 (6289): aad7993. The article was chosen for Icahn School of Medicine at Mount Sinai press releases on 4/28/2016.

N. M. Lubaki*, P. Younan*, R. I. Santos, M. Meyer, M. Iampietro, R. A. Koup, and A. Bukreyev. (2016). The Ebola interferon inhibiting domains attenuate and dysregulate cell-mediated immune responses. PLOS Pathogens 21(12):e1006031. The article was chosen for UTMB press releases on 12/01/2016. *Co-lead authors.

I. V. Kuzmin, T. M. Schwarz, P. A. Ilinykh, I. Jordan, T. G. Ksiazek, R. Sachidanandam, C. F. Basler, and A. Bukreyev (2017). Innate immune response of bat and human cells to filoviruses: commonalities and distinctions. J. Virol. 91(8):e02471-16.

P. Luthra, S. Aguirre, M. T. Sanchez, B. C. Yen, C. A. Pietzsch, B. Tigabu, L. Morlock, A. Garcia-Sastre, A. Sesma, N. Williams, A. Bukreyev, D. W. Leung, and C. Basler. (2017). Topoisomerase II inhibitors induce DNA Damage dependent interferon responses circumventing Ebola virus immune evasion. mBio. 8(2) e00368-17.

T. S. Postler, A. N. Clawson, G. K. Amarasinghe, C. F. Basler, S. Bavari, M. Benko, K. R. Blasdell, T. Briese, M. J. Buchmeier, A. Bukreyev et al. (2017). Possibility and challenges of conversion of current virus species names to Linnaean Binomials. Syst. Biol. 66(3): 463-473.

Y. Bao, G. K. Amarasinghe, C. F. Basler, S. Bavari, A. Bukreyev, K. Chandran, O. Dolnik, J. M. Dye, H. Ebihara, P. Formenty, R. Hewson, G. P. Kobinger, E. M. Leroy, E. Muhlberger, S. V. Netesov, J. L. Patterson, J. T. Paweska, S. J. Smither, A. Takada, J. S. Towner, V. E. Volchkov, V. Wahl-Jensen, and J. H. Kuhn. (2017). Implementation of objective PASC-derived taxon demarcation criteria for official classification of Filoviruses. Viruses 9(5): E106.

G. Liu, P. Nash, B. Johnson, C. Pietzsch, M. Ilagan, A. Bukreyev, C. Basler, T. Bowlin, D. Moir, D. Leung, and G. Amarasinghe. (2017). A sensitive in vitro high-throughput screen to identify pan-filoviral replication inhibitors targeting the VP35-NP interface ACS Infectious Diseases, 3(3):190-198.

G. K. Amarasinghe, Y. Bao, C. F. Basler, S. Bavari, M. Beer, N. Bejerman, K. R. Blasdell, A. Bochnowski, T. Briese, A. Bukreyev et al. (2017). Taxonomy of the order Mononegavirales: Update 2017. Arch. Virol. 162(8):2493-2504.

P. Younan, P. Ramanathan, J. Graber, F. Gusovsky, and A. Bukreyev. (2017). The TLR4 antagonist Eritoran protects mice from lethal filovirus challenge. mBio 8(2) e00226-17.

J. H. Kuhn, G. K. Amarasinghe, C. F. Basler, S. Bavari, A. Bukreyev, K. Chandran, O. Kolnik, J. M. Dye, H. Ebihara, P. Formenty, R. Hewson, G. P. Kobinger, E. M. Leroy, E. Muhlberger, S. V. Netesov, J. L. Patterson, J. T. Paweska, S. J. Smither, A. Takada, J. S. Towner, V. E. Volchkov, V. Wahl-Jensen, and ICTV Report Consortium. (2017). Family Filoviridae: Classification and features. ICTV, Viruses, in press.

M. Iampietro*, P. Younan*, A. Nishida, M. Dutta, N. M. Lubaki, R. I. Santos, R. A. Koup, M. G. Katze, and A. Bukreyev. (2017). Ebola virus glycoprotein directly triggers T lymphocyte death despite of the lack of infection. PLOS Pathogens PPATHOGENS-D-16-02653 published on 5/22/2017. The article was chosen for UTMB press releases on 05/24/2017. *Co-lead authors.

N. M. Lubaki, P. Younan, R. I. Santos, M. Meyer, M. Iampietro, R. A. Koup, and A. Bukreyev. (2016). The Ebola interferon inhibiting domains attenuate and dysregulate cell-mediated immune responses. PLOS Pathogens 21(12):e1006031. The article was chosen for UTMB press releases on 12/01/2016.

I. V. Kuzmin, T. M. Schwarz, P. A. Ilinykh, I. Jordan, T. G. Ksiazek, R. Sachidanandam, C. F. Basler, and A. Bukreyev (2017). Innate immune response of bat and human cells to filoviruses: commonalities and distinctions. J. Virol. 91(8):e02471-16.

P. Younan, P. Ramanathan, J. Graber, F. Gusovsky, and A. Bukreyev. (2017). The TLR4 antagonist Eritoran protects mice from lethal filovirus challenge. mBio 8(2) e00226-17.

M. Iampietro, P. Younan, A. Nishida, M. Dutta, N. M. Lubaki, R. I. Santos, R. A. Koup, M. G. Katze, and A. Bukreyev. (2017). Ebola virus glycoprotein directly triggers T lymphocyte death despite of the lack of infection. PLOS Pathogens PPATHOGENS-D-16-02653 published on 5/22/2017. The article was chosen for UTMB press releases on 05/24/2017.