Virologie


Arbeitsgruppe PD Dr. rer. nat. Hanna-Mari Baldauf

Das VIIRAL Labor fokussiert sich auf die Untersuchung spezies-spezifischer Antworten der angeborenen Immunität im Kontext von retroviralen Infektionen als auch therapeutischen Möglichkeiten für die Akute Leukämie. Im ersten Schwerpunkt verwenden wir verschiedene Modellsysteme von einfachen Retroviren bis hin zu komplexen Lentiviren, wie HIV, um mehr Einblick in die spezies-spezifischen Unterschiede der angeborenen Immunität zu gewinnen. Basierend auf unseren Vorarbeiten hinsichtlich antiviraler Proteine als auch unserer Erkenntnis, dass Kaninchen weniger Barrieren gegenüber einer HIV Replikation aufweisen als Mäuse und Ratten, arbeiten wir daran ein voll permissives transgenes Kaninchen-Modell zu entwickeln, um neue Ansatzpunkte für die Prävention oder Therapie von HIV/AIDS generieren zu können. Im zweiten Schwerpunkt untersuchen wir, basierend auf unseren Vorarbeiten an antiviralen Proteinen, die auch in der Krebsforschung relevant sind, verschiedene therapeutische Ansätze für die Akute Leukämie.

zur Arbeitsgruppe

Leitung

PD Dr. rer. nat. Hanna-Mari Baldauf

Hanna-Mari Baldauf, PhD, is a principal investigator at the Max von Pettenkofer Institute & Gene Center, Virology, of the LMU Munich. She obtained a Bachelor of Science (BSc (Hons)) degree in Biotechnology at the University of Applied Sciences in Mannheim and a Master of Science (MSc) degree in Biomedicine at the Johannes-Gutenberg University in Mainz. She was trained as a PhD in virology at the Ruprecht-Karls-University in Heidelberg. After a short-term DAAD postdoctoral period at the Haartman Institute in Helsinki, Finland, and postdoctoral period at the Ruprecht-Karls-University in Heidelberg, she was appointed staff scientist at the Institute for Medical Virology at the University Hospital of the Goethe-University in Frankfurt a. M. (2012 to 2015). In 2016 she started her own research group at the Max von Pettenkofer Institute in Munich and completed her habilitation in Experimental Virology in 2019. Since summer 2021 she is spokesperson of the young Society for virology (jGfV) and since fall 2022 also official board member of the Society for virology (GfV).

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AG-Mitglieder

Aktuelle Gruppenmitglieder

Hanna-Mari Baldauf, PhD, principal investigator
E-Mail: baldauf@mvp.lmu.de
Phone: +49 89 2180-78022

Selin Aidin, MD student
E-Mail: aidin@mvp.lmu.de
Phone: +49 89 2180 78068

Alexandra Koch, PhD student
E-Mail: Koch@mvp.lmu.de
Phone: +49 89 2180 78068

Yanis Pignot, Master student
E-Mail: pignot@mvp.lmu.de
Phone: +49 89 2180 78068

Alejandro Salinas Illarena, PhD student
E-Mail: salinas@mvp.lmu.de
Phone: +49 89 2180 78068

Luca Schelle, PhD student
E-Mail: schelle@mvp.lmu.de
Phone: +49 89 2180 78068

João Vasco Côrte-Real, PhD student
E-Mail: cortereal@mvp.lmu.de
Phone +49 89 2180 78068

Ehemalige Labormitglieder

  • Valentin Bärreiter (MSc internship student)
  • Ning Ding (MSc internship student)
  • Deniz Eser (MSc internship student)
  • Adrian Fröhlich (MSc student)
  • Madeleine Gapp (MSc student)
  • Sagarika Gosh (MSc internship student)
  • LiYing Huang (MSc internship student)
  • Pauliina Junttila (MSc student)
  • Caroline Kliem (MSc student)
  • Lea Knez (MSc internship student)
  • Tobias Komar (MSc internship student)
  • Fabian Kriesel (MSc student)
  • Philipp Leopoldseder (MSc internship student)
  • Srujita Mahankali (MSc student)
  • Bhavna Menon (MSc internship student)
  • Ramya Nair (PhD student)
  • Margarita Shnipova (MSc internship student)
  • Putri Soedarsono (BSc student)
  • Patrícia de Sousa Pereira (PhD student)
  • Lu Zhang (MSc student)
  • Anthony Ao, MSc internship student
  • Mihai-Alin Baur, MSc internship student
  • Augusto del Pozo Ben, technician
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Forschung

Species-specific innate immunity and animal model development

The human immunodeficiency virus type 1 (HIV-1) has become one of the most devastating pandemics in recorded history. Currently, 38 million people are living with HIV-1 and about 680.000 died of AIDS in 2020 alone (unaids.org). Until now, no protective vaccine against HIV is in sight and currently available pharmacotherapies can only partly control, but not cure infection. The thus imperative development of alternative strategies against HIV has been hampered by the lack of small animal models that are highly permissive to infection.

​An immunocompetent, permissive small animal model would be valuable for the study of HIV-1 pathogenesis and for the testing of drug and vaccine candidates. One approach are the widely used HIV xenotransplant models. Another alternative is the identification and surmounting of species-specific barriers that HIV encounters along its replication cycle in cells from small animals. These species-specific barriers are either due to missing/non-functional cellular co-factors, which HIV-1 hijacks at different steps of its life cycle for efficient replication, or due to the presence of restriction factors, which block HIV-1 replication at distinct steps and cannot be counteracted by accessory HIV proteins.

 

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​Therefore, we, the VIIRAL lab, want to understand how innate immunity factors work in a species-specific context – identifying thereby specific signaling pathways and motifs, which are involved to elucidate the mode of action of the immunity factors, and how the virus antagonizes them. Building on our previous work on innate immunity factors (Tervo et al., 2008; Tervo et al., 2011; Baldauf et al., 2012; Baldauf et al., 2017) as well as our observation that rabbits as a species display fewer blocks to HIV-1 replication than mice or rats (Tervo and Keppler, 2010), we want to develop a fully permissive transgenic rabbit model to find novel strategies for the prevention or treatment of HIV/AIDS.

Next to our efforts to advance a rabbit model for HIV infection, we want to study restriction factors and their relevance in different animal models. We use Murine Leukemia Virus (MLV), a simple retrovirus, to study retroviral infection and its restriction in a more physiological setting. One of the factors our group has been interested in for the last years is Serine Incorporator 5 (SERINC5). This mammalian membrane protein has been shown to negatively affect HIV infectivity in the absence of the HIV accessory protein Nef (Pereira et al., 2019; Kriesel et al., 2020). Currently, we are investigating the effect of SERINC5 orthologs on MLV, both in the presence and absence of MLV GlycoGag that has already been shown to overcome SERINC5-imposed restriction in Nef deficient HIV (Pereira et al., 2019).

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Acute leukemia

Acute myeloid leukemia (AML) is an aggressive cancer of the blood, where malignant myeloid blasts accumulate in the bone marrow. One of the challenges of effective AML treatment is resistance to cytarabine (or ara-C), a standard AML chemotherapeutic drug used in front-line treatment today (Nair et al., 2021).

 

In 2017, Schneider et al. reported the dNTPase sterile alpha motif and HD-domain-containing protein 1 (SAMHD1) to be a targetable biomarker for ara-C treatment response (Schneider, Oellerich, Baldauf et al., 2017). The intracellular triphosphorylated active form of ara-C, ara-CTP, is recognized as a substrate by SAMHD1, which leads to a decrease in the amount of ara-CTP within the cells and consequently reduced cytotoxicity (Schneider, Oellerich, Baldauf et al. 2017).​

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SAMHD1 can be targeted by the lentiviral accessory protein Vpx for proteasomal degradation by interacting with the proteasomal degradation complex and SAMHD1. We in the VIIRAL lab aim to use Vpx to target SAMHD1 in AML cells to improve ara-C sensitivity.

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Publikationen

Top 10 Publikationen

Schelle L, Côrte-Real JV, Fayyaz S, Del Pozo Ben A, Shnipova M, Petersen M, Lotke R, Menon B, Matzek D, Pfaff L, Pinheiro A, Marques JP, Melo-Ferreira J, Popper B, Esteves PJ, Sauter D, Abrantes J, Baldauf HM. Evolutionary and functional characterization of lagomorph guanylate-binding proteins: a story of gain and loss and shedding light on expression, localization and innate immunity-related functions. Front Immunol. 15:1303089 (2024) https://doi: 10.3389/fimmu.2024.1303089.
Schelle L, Côrte-Real JV, Esteves PJ, Abrantes J, Baldauf HM. Functional cross-species conservation of guanylate-binding proteins in innate immunity. Medical Microbiology and Immunology. 13:1-12 (2022) https://doi: 10.1007/s00430-022-00736-7.
Côrte-Real JV, Baldauf HM, Melo-Ferreira J, Abrantes J, Esteves PJ. Evolution of Guanylate Binding Protein (GBP) Genes in Muroid Rodents (Muridae and Cricetidae) Reveals an Outstanding Pattern of Gain and Loss. Frontiers in Immunology. 13:752186 (2022) https://doi: 10.3389/fimmu.2022.752186.
Rothenburger T, Thomas D, Schreiber Y, Wratil PR, Pflantz T, Knecht K, Digianantonio K, Temple J, Schneider C, Baldauf HM, McLaughlin KM, Rothweiler F, Bilen B, Farmand S, Bojkova D, Costa R, Ferreirós N, Geisslinger G, Oellerich T, Xiong Y, Keppler OT, Wass MN, Michaelis M, Cinatl J Jr. Journal of Experimental and Clinical Cancer Research. 40(1):317 (2021) https://doi: 10.1186/s13046-021-02093-4.
Nair R, Salinas-Illarena A, Baldauf HM. New strategies to treat AML: novel insights into AML survival pathways and combination therapies. Leukemia. 35(2):299-311 (2021) https://doi: 10.1038/s41375-020-01069-1.
de Sousa-Pereira P, Abrantes J, Bauernfried S, Pierini V, Esteves PJ, Keppler OT, Pizzato M, Hornung V, Fackler OT, Baldauf HM. The antiviral activity of rodent and lagomorph SERINC3 and SERINC5 is counteracted by known viral antagonists. Journal of General Virology. 100(2):278-88 (2019) https://doi: 10.1099/jgv.0.001201.
Baldauf HM, Stegmann L, Schwarz SM, Ambiel I, Trotard M, Martin M, et al. Vpx overcomes a SAMHD1-independent block to HIV reverse transcription that is specific to resting CD4 T cells. Proceedings of the National Academy of Sciences. 114(10):2729-34 (2017) https://doi: 10.1073/pnas.1613635114.
Schneider C, Oellerich T, Baldauf HM, Schwarz SM, Thomas D, Flick R, Bohnenberger H, Kaderali L, Stegmann L, Cremer A, Martin M, Lohmeyer J, Michaelis M, Hornung V, Schliemann C, Berdel WE, Hartmann W, Wardelmann E, Comoglio F, Hansmann ML, Yakunin AF, Geisslinger G, Ströbel P, Ferreirós N, Serve H, Keppler OT, Cinatl J Jr. SAMHD1 is a biomarker for cytarabine response and a therapeutic target in acute myeloid leukemia. Nature Medicine. 23(2):250-5 (2017) https://doi: 10.1038/nm.4255.
Baldauf HM, Pan X, Erikson E, Schmidt S, Daddacha W, Burggraf M, Schenkova K, Ambiel I, Wabnitz G, Gramberg T, Panitz S, Flory E, Landau NR, Sertel S, Rutsch F, Lasitschka F, Kim B, König R, Fackler OT, Keppler OT. SAMHD1 restricts HIV-1 infection in resting CD4(+) T cells. Nature Medicine. 18(11):1682-7 (2012) https://doi: 10.1038/nm.2964.
Tervo HM, Keppler OT. High natural permissivity of primary rabbit cells for HIV-1, with a virion infectivity defect in macrophages as the final replication barrier. Journal of Virology. 84(23):12300-14 (2010) https://doi: 10.1128/jvi.01607-10.

Auszeichnungen

Auszeichnungen für Gruppenmitglieder

  • ACHIEVE ROUND scholarship (2024): João Vasco Côrte-Real
  • Best jGfV Fall paper award (2023): Luca Schelle
    Joachim Herz Add-on fellowship (2022): Alejandro Salinas
  • jGfV lab rotation scholarship (2022): Luca Schelle
  • 3rd place, 3-Minute Thesis competition; Laboratory of Molecular Biology, Cambridge
    UK & Max Planck Institute of Biochemistry, Martinsried (2022): Ramya Nair
  • PhD Fellowship of the Studienstiftung des dt. Volkes (2021): Alejandro Salinas
  • PhD Fellowship of the Fundacao para Ciencia e Tecnologia (FCT) Portugal (2020): João Vasco Côrte-Real
  • Mentee of the “Momente“-mentoring program of the LMU (2021-2022): Hanna-Mari Baldauf
  • 2nd poster prize at Interact Munich (2020): Ramya Nair
  • PhD Fellowship of the Fundação para a Ciência e Tecnologia (FCT), Portugal (2014-2018): Patrícia Pereira
  • Postdoctoral award in Virology of the Robert Koch-Foundation (2013): Hanna-Mari Baldauf