The Bukreyev Lab

The Bukreyev 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) and Dr. Raul Andino (UCSF).

Lab Members

Dr. Alex Bukreyev alexander.bukreyev@utmb.edu
Dr. Kai Huang kahuang@utmb.edu
Dr. Philipp Ilinykhpailinyk@utmb.edu
Dr. Michelle Meyermnmeyer@utmb.edu
Ms. Colette Peitzsch (Lab Manager) capietzs@utmb.edu
Dr. Palaniappan Ramanathanparamana@utmb.edu
Dr. Abhi Prasadabnprasa@utmb.edu
Mr. Adam Ronk ajronk@utmb.edu
Dr. Khaled Sabryksmohame@utmb.edu
Dr. Rodrigo Santosroimarqu@utmb.edu
Ms. Dora Salinas (Administrative Assistant)dasalina@utmb.edu

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. Mühlberger, 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. Bào, 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. Bào, 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. Bào, 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.

P. Younan, M. Iampietro, A. Nishida, P. Ramanathan, R. I. Santos, M. Dutta, N. M. Lubaki, R. A. Koup, M. G. Katze, and A. Bukreyev. (2017). Ebola binding to Tim-1 on T-Lymphocytes induces a cytokine storm. mBio 8(5) e00845-17. The article was chosen for American Society of Microbiology and UTMB press releases on 09/26/2017.

L. B. King, M. L. Fusco, A. I. Flyak, P. A. Ilinykh, K. Huang, B. Gunn, R. N. Kirchdoerfer., K. M. Hastie, A. Sangha, J. Meiler, G. Alter, A. Bukreyev, J. E. Crowe, Jr., and E. Ollmann Saphire. (2018) Therapeutic human monoclonal antibody MR191against Marburg virus targets a conserved site to block receptor binding. Cell Host & Microbe 23(1):101-109.

M. Meyer, E. Huang, O. Yuzhakov, P. Ramanathan, G. Ciaramella, and A. Bukreyev. (2019) Modified mRNA-based vaccines elicit robust immune responses and protect guinea pigs from Ebola virus disease. J. Infect. Dis. 217(2):451-455.

M. Meyer, E. Huang, O. Yuzhakov, P. Ramanathan, G. Ciaramella, and A. Bukreyev (2018) Modified mRNA-based vaccines elicit robust immune responses and protect guinea pigs from Ebola virus disease. J. Infect. Dis. 217(2):451-455.

P. Luthra, J. Liang, C. A. Pietzsch, S Khadka, M. R. Edwards, S. Wei, S. De, B. Posner, A. Bukreyev, J. M. Ready and C. F. Basler (2018). A high throughput screen identifies benzoquinoline compounds as inhibitors of Ebola virus replication. Antiviral Research 150:193-201. 

P. Younan, M. Iampietro and A. Bukreyev (2018). Disabling of lymphocyte immune response by Ebola Virus. PLOS Pathogens 14(4):e1006932.

G. K. Amarasinghe, N. A. Ceballos, A. C. Banyard, C. F. Basler, S. Bavari, A. J. Bennett, K. R. Blasdell, T. Briese, A. Bukreyev, Y. Cai, et al. (2018). Taxonomy of the order Mononegavirales: update 2018. Archives of Virology 163(8):2283-2294.

E. O. Saphire, S. L. Schendel, M. L. Fusco, K. Gangavarapu, B. M. Gunn, A. Z. Wec, P. J. Halfmann, J. M. Brannan, A. S. Herbert, X. Qio et al. (2018). Systematic analysis of monoclonal antibodies against Ebola virus GP defines features that contribute to protection. Cell 174(4):938-952.

A. I. Flyak, N. Kuzmina, C. D. Murin, C. Bryan, E. Davidson, P. Gilchuk, C. P. Gulka, P. A. Ilinykh, X. Shen, P. Ramanathan, K. Huang, H. Turner, M. L. Fusco, R. Lampley, N. Kose, H. King, G. Sapparapu, B. J. Doranz, T. G. Ksiazek, D. W. Wright, E. Ollmann Saphire, A. B. Ward, A. Bukreyev*, and J. E. Crowe*, Jr. (2018). Neutralizing antibodies from human survivors target a conserved site in the ebolavirus glycoprotein HR2/MPER regions. *Co-corresponding author. Nature Microbiology 3(6):670-677.

P. Gilchuk, N. Kuzmina, P. A. Ilinykh, K. Huang, B. M. Gunn, A. Bryan, E. Davidson, B. J. Doranz, H. L. Turner, M. L. Fusco, M. S. Bramble, N. A. Hoff, E. Binshtein, N. Kose, A. I. Flyak,, R. Flinko, C. Orlandi, R. Carnahan, E. H. Parrish, A. M. Sevy, R. G. Bombardi, P. K. Singh, P. Mukadi, J. J. Muyembe-Tamfum, M. D. Ohi, E. Ollmann Saphire , G. K. Lewis, G. Alter, A. B. Ward, A. W. Rimoin, A. Bukreyev*, and J. E. Crowe, Jr*. (2018). Multifunctional pan-ebolavirus antibodies recognize a site of broad vulnerability on the ebolavirus glycoprotein. Immunity 49(2):363-374. *Co-corresponding author. The article was chosen for NIAID press releases on 07/17/2018.

M. Meyer, A. Yoshida, P. Ramanathan, E. Ollmann Saphire, P. Collins, J. E. Crowe Jr., S. Samal and A. Bukreyev (2018). Antibody repertoires to the same Ebola vaccine antigen are differentially affected by vaccine vectors. Cell Reports 24: 1816-1829.

N. A. Kuzmina, P. Younan, P. Gilchuk, R. I. Santos, A. I. Flyak, P. A. Ilinykh, K. Huang,   N. M. Lubaki, P. Ramanathan, J. E. Crowe, Jr. and A. Bukreyev (2018). Antibody-Dependent Enhancement of Ebola Virus Infection by Human Antibodies Isolated from Survivors. Cell Reports 24: 1802-1815.

M. Iampietro, R. I. Santos, N. M. Lubaki and A. Bukreyev (2018). Ebola Virus Shed GP Triggers Differentiation, Infection and Death of Monocytes Through TLR4 Activation. Journal of Infectious Diseases 218(Suppl. 5): S327-S334.

T. Ammosova, C. A. Pietzsch, Y. Saygideğer, A. Ilatovsky, X. Lin, A. Ivanov, N. Kumari, M. Jerebtsova, A. Kulkarni, M. Petukhov, A. Üren, A. Bukreyev* and Sergei Nekhai* (2018). Protein phosphatase-1-targeting small molecule C31 inhibits Ebola virus replication. Journal of Infectious Diseases 218 (Suppl. 5): S627-S635. *Co-corresponding author.

P. A. Ilinykh, J. Graber, N. A. Kuzmina, K. Huang, T. G. Ksiazek, J. E. Crowe, Jr. and A. Bukreyev (2018). Ebolavirus chimerization for the development of a mouse model for screening of Bundibugyo-specific antibodies. Journal of Infectious Diseases 218 (Suppl. 5): S418-S422.

P. A. Ilinykh, R. I. Santos, B. M. Gunn, N. A. Kuzmina, X. Shen, K. Huang, P. Gilchuk, A. I. Flyak, P. Younan, G. Alter, J. E. Crowe, Jr., and A. Bukreyev (2018). Assymetric antiviral effects of ebolavirus antibodies targeting glycoprotein stem and glycan cap. PLOS Pathogens 14(8):e1007204.

P. Younan, M. Iampietro, R. I. Santos, P. Ramanathan, V. L. Popov and A. Bukreyev (2018). Role of TMEM16F in the incorporation phosphatidylserine into budding ebolavirus virions. Journal of Infectious Diseases 218 (Suppl. 5): S335-S345.

P. Younan, M. Iampietro, R. I. Santos, P. Ramanathan, V. L. Popov and A. Bukreyev (2018). Disruption of phosphatidylserine synthesis or trafficking reduces infectivity of Ebola virus. Journal of Infectious Diseases 218 (Suppl. 5): S475-S485.

B. Tigabu, P. Ramanathan, A. Ivanov, X. Lin, P. A. Ilinykh, C. S. Parry, A. N. Freiberg, S. Nekhai and A. Bukreyev (2018). Phosphorylated VP30 of Marburg Virus is a Repressor of Transcription. Journal of Virology JVI00426-18R2 in press.

M. Meyer, D. C. Malherbe and A. Bukreyev (2018). Can Ebola virus vaccines have universal correlates of protection? Trends in Microbiology TIMI-D-18-00114R1 in press.

P. Luthra, J. Naidoo, C. A. Pietzsch, M. R. Edwards, S. De, S. Khadka, M. Anantpadma, R. A. Davey, A. Bukreyev, J. M. Ready and C. F. Basler (2018). Inhibiting pyrimidine biosynthesis impairs Ebola virus replication through depletion of nucleoside pools and activation of innate immune responses. Antiviral Research 158:288-302.

J. Fang, C. Pietzsch, P. Ramanathan, R. I. Santos, P. A. Ilinykh, M. A. Garcia-Blanco, A. Bukreyev and S. S. Bradrick (2018). Staufen1 interacts with multiple components of the Ebola virus ribonucleoprotein and enhances viral RNA synthesis. mBio 9(5): e01771-18.

J. B. Kimble, D. C. Malherbe, M. Meyer, B. M. Gunn, M. M. Karim, P. A. Ilinykh, M. Iampietro, K. S. Mohamed, S. Negi, P. Gilchuk, K. Huang, Y I. Wolf, W. Braun, J. E. Crowe Jr., G. Alter, A. Bukreyev (2018). Antibody-mediated protective mechanisms induced by a trivalent parainfluenza-vectored ebolavirus vaccine. Journal of Virology JVI01845-18R1 in press.