Adam Hume

Research Assistant Professor, Virology, Immunology & Microbiology

New viruses are being discovered at a rapidly increasing rate by virtue of next generation sequencing of wildlife samples, including many viruses closely related to some of the deadliest emerging and reemerging viruses. In just the last dozen years, 9 new filoviruses have been discovered, all with unknown pathogenic potential. One of my main research interests involves characterizing differential host responses to pathogenic viruses and closely related non-pathogenic viruses to both be able to assess the possible pathogenicity of novel viruses as well as to try to target host response pathways involved in these divergent responses as potential points of therapeutic intervention.

My work focuses on some of the deadliest human pathogens, most notably filoviruses such as Ebola and Marburg viruses.  Owing to the devasting disease and high mortality rates they cause, study of these viruses requires a Biosafety Level 4 (BSL4) laboratory such as the BSL4 facility we have at the NEIDL.

One roadblock to the study of these new viruses related to highly pathogenic emerging and reemerging viruses is that most of these viruses have not yet been cultured.  While creating recombinant viruses through reverse genetics approaches would seem to be a solution to this issue, a second barricade to these studies often prevents this: most viral genomes identified by next generation sequences lack terminal genomic sequences.  These portions of the genome typically include sequences necessary for viral genomic replication and transcription, making rescue impossible in the absence of these sequences.

Lloviu virus, a filovirus first discovered in 2011 by sequencing of bat carcasses found in caves in Spain in 2002, represents such a virus.  While Lloviu virus was recently isolated from Schreibers bats in Hungary (Kemenesi et al., 2022), it had not been cultured previously and sequence was missing from both ends of the genome.  Using reverse genetics tools, including a previously developed Lloviu virus minigenome system, we were able to complement missing genomic sequences and rescue recombinant Lloviu virus and begin to study this virus (Hume et al., 2022) prior to it being cultured.  As with all filovirus work, these studies were performed in our BSL4 facility.  Importantly, we are now comparing our recombinant Lloviu virus to see how well it mirrors wild-type Lloviu virus. If these viruses behave similarly, this could provide a new blueprint for rescuing and determining the pathogenic potential of many viruses which may pose a risk to human health should a spillover event occur.

While animal models have undoubtedly provided important information with regards to viral pathogenesis and transmission, the fact that there are many antiviral drugs and therapies that have been shown to be effective in animals but not in humans has made the need to develop and use human systems to study virus-induced host responses and correlates of pathogenicity self-evident. To this end, my research is focused on using these systems, including human primary cells, primary-based human organoids, and induced pluripotent stem cell (iPSC)-derived cells and organoids to study viral replication and pathogenesis. Collaborating with tissue engineers including researchers at Boston University’s Center for Regenerative Medicine (CReM), we have begun to explore how viruses manipulate these systems. Using transcriptional and phosphoproteomic approaches to study these systems, we are uncovering key pathways necessary for viral replication, allowing for targeted small molecular inhibition of host pathways to block viral replication. Using viruses of differing pathogenicity, we hope to also identify virulence markers in order to assess the potential pathogenicity of novel viruses which have not yet been known to spill over to the human population.

Recent representative publications

  1. Kemenesi G, Tóth G, Mayora-Neto M, Scott S, Temperton N, Wright E, Mühlberger E, Hume AJ, Zana B, Boldogh SA, Görföl T, Estók P, Lanszki Z, Somogyi BA, Nagy A, Pereszlényi CI, Dudás G, Földes F, Kurucz K, Madai M, Zeghbib S, Jakab F. Isolation of infectious Lloviu virus from Schreiber’s bats in Hungary. Nat Commun. 2022 Mar 31;13, 1706(2022). doi: 10.1038/s41467-022-29298-1.
  2. Hume AJǂ, Heiden B, Olejnik J, Suder EL, Ross S, Scoon WA, Bullitt E, Ericsson M, White MR, Turcinovic J, Thao TTN, Hekman RM, Kaserman JE, Huang J, Alysandratos KD, Toth GE, Jakab F, Kotton DN, Wilson AA, Emili A, Thiel V, Connor JH, Kemenesi G, Cifuentes D, Mühlberger Eǂ. Recombinant Lloviu virus as a tool to study viral replication and host responses. PLoS Pathog. 2022 Feb 4;18(2):e1010268. doi: 10.1371/journal.ppat.1010268. PMID: 35120176; PMCID: PMC8849519 ǂdenotes corresponding author
  3. Wang R*, Hume AJ*, Beermann ML, Simone-Roach C, Lindstrom-Vautrin J, Le Suer J, Huang J, Olejnik J, Villacorta-Martin C, Bullitt E, Hinds A, Ghaedi M, Rollins S, Werder RB, Abo KM, Wilson AA, Mühlberger E, Kotton DN, Hawkins FJ. Human airway lineages derived from pluripotent stem cells reveal the epithelial responses to SARS-CoV-2 infection. Am J Physiol Lung Cell Mol Physiol. 2022 Jan 12. doi: 10.1152/ajplung.00397.2021. Epub ahead of print. PMID: 35020534 *denotes shared first authorship
  4. Leon J, Michelson DA, Olejnik J, Chowdhary K, Oh HS, Hume AJ, Galván-Peña S, Zhu Y, Chen F, Vijaykumar B, Yang L, Crestani E, Yonker LM, Knipe DM, Mühlberger E, Benoist C. A virus-specific monocyte inflammatory phenotype is induced by SARS-CoV-2 at the immune-epithelial interface. Proc Natl Acad Sci USA. 2022 Jan 4;119(1):e2116853118. doi: 10.1073/pnas.2116853118. PMID: 34969849.
  5. Mithal A*, Hume AJ*, Lindstrom-Vautrin J, Villacorta-Martin C, Olejnik J, Bullitt E, Hinds A, Mühlberger E, Mostoslavsky G. Human Pluripotent Stem Cell-Derived Intestinal Organoids Model SARS-CoV-2 Infection Revealing a Common Epithelial Inflammatory Response. Stem Cell Reports. 2021 Apr 13;16(4):940-953. doi: 10.1016/j.stemcr.2021.02.019. PMID: 33852884 *denotes shared first authorship
  6. Hekman RM*, Hume AJ*, Goel RK*, Abo KM*, Huang J*, Blum BC*, Werder RB*, Suder EL*, Paul I*, Phanse S, Youssef A, Alysandratos KD, Padhorny D, Ojha S, Mora-Martin A, Kretov D, Ash P, Varma M, Zhao J, Patten JJ, Villacorta-Martin C, Bolzan D, Perea-Resa C, Bullitt E, Hinds A, Tilston-Lunel A, Varelas X, Farhangmehr S, Braunschweig U, Kwan JH, McComb M, Basu A, Saeed M, Perissi V, Burks EJ, Layne MD, Connor JH, Davey R, Cheng JX, Wolozin BL, Blencowe BJ, Wuchty S, Lyons SM, Kozakov D, Cifuentes D, Blower M, Kotton DN, Wilson AA, Mühlberger E, Emili A. Actionable Cytopathogenic Host Responses of Human Alveolar Type 2 Cells to SARS-CoV-2. Mol Cell. 2020 Nov 19: S1097-2765(20)30828-5. doi: 10.1016/j.molcel.2020.11.028. PMID: 33259812 *denotes shared first authorship
  7. Huang J*, Hume AJ*, Abo KM*, Werder RB*, Villacorta-Martin C, Alysandratos KD, Beermann ML, Simone-Roach C, Lindstrom-Vautrin J, Olejnik J, Suder EL, Bullitt E, Hinds A, Sharma A, Bosmann M, Wang R, Hawkins F, Burks EJ, Saeed M, Wilson AA, Mühlberger E, Kotton DN. SARS-CoV-2 Infection of Pluripotent Stem Cell-Derived Human Lung Alveolar Type 2 Cells Elicits a Rapid Epithelial-Intrinsic Inflammatory Response. Cell Stem Cell. 2020 Dec 3;27(6):962-973.e7. doi: 10.1016/j.stem.2020.09.013. Epub 2020 Sep 18. PMID: 32979316 *denotes shared first authorship
  8. Bruchez A, Sha K, Johnson J, Chen L, Stefani C, McConnell H, Gaucherand L, Prins R, Matreyek KA, Hume AJ, Mühlberger E, Schmidt EV, Olinger GG, Stuart LM, Lacy-Hulbert A. MHC class II transactivator CIITA induces cell resistance to Ebola virus and SARS-like coronaviruses. Science. 2020 Aug 27: eabb3753. doi: 10.1126/science.abb3753. PMID: 32855215.
  9. Hume AJ, Mühlberger E. Distinct Genome Replication and Transcription Strategies within the Growing Filovirus Family. J Mol Biol. 2019 Oct 4;431(21):4290-4320. doi: 10.1016/j.jmb.2019.06.029. Epub 2019 Jun 29. Review. PMID: 31260690
  10. Olejnik J, Mühlberger E, Hume AJǂ. Recent advances in Marburgvirus research. F1000Res. 2019 May 21; 8: F1000 Faculty Rev-704. PMID: 31131088 ǂdenotes corresponding author
  11. Deflubé LR*, Cressey TN*, Hume AJ*, Olejnik J, Haddock E, Feldmann F, Ebihara H, Fearns R, Mühlberger E. Ebolavirus polymerase uses an unconventional genome replication mechanism. Proc Natl Acad Sci USA. 2019 Apr 23;116(17):8535-8543. doi: 10.1073/pnas.1815745116. Epub 2019 Apr 8. PMID: 30962389 *denotes shared first authorship
  12. Manhart WA, Pacheco JR, Hume AJ, Cressey TN, Deflubé LR, Mühlberger E. A Chimeric Lloviu Virus Minigenome System Reveals that the Bat-Derived Filovirus Replicates More Similarly to Ebolaviruses than Marburgviruses. Cell Rep. 2018 Sep 4; 24(10): 2573-2580. PMID 30184492
  13. Hume A, Mühlberger E. Marburg Virus Viral Protein 35 Inhibits Protein Kinase R Activation in a Cell Type-Specific Manner. J Infect Dis. 2018 Nov 22; 218(suppl_5): S403-S408. PMID 30165526
  14. Nelson EV*, Pacheco JR*, Hume AJ*, Cressey TN, Deflubé LR, Ruedas JB, Connor JH, Ebihara H, Mühlberger E. An RNA polymerase II-driven Ebola virus minigenome system as an advanced tool for antiviral drug screening. Antiviral Res. 2017 Oct; 146: 21-27. PMID 28807685 *denotes shared first authorship

For a comprehensive list of my publications, click here.

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