Alexander Hahn, Dr. rer. nat.; Anna Großkopf, Dr. rer. nat.; Bojan Hörnich, M. Sc (graduated as Dr. rer. nat., current position at DLR).; Sarah Schlagowski, TA; Dr. Thomas Fricke (PhD); Stefano Scribano, M. Sc.
KSHV and RRV
We are studying the human pathogen Kaposi’s sarcoma-associated herpesvirus (KSHV), a gamma2-herpesvirus or rhadinovirus, and the related rhesus monkey rhadinovirus (RRV), a similar virus of rhesus macaques. KSHV is a tumor virus. It is associated with Kaposi’s sarcoma and two B cell malignancies, primary effusion lymphoma and multicentric Castleman’s disease. KSHV causes significant morbidity and mortality in Sub-Saharan Africa and in the context of HIV infection.
A major focus of our research is on the interaction of viral glycoproteins with cellular receptors. These receptor interactions are critical for entry of the virus into host cells and constitute a major determinant of viral tropism, governing which cell types and which tissues are targeted by the virus. We are using our knowledge about specific virus-receptor interactions to generate modified viruses that are defective in the use of certain receptors or that exhibit altered cell and tissue tropism. In the long run we want to apply these modified viruses as experimental vaccines and vaccine vectors.
A second focus is on the function of the cellular receptors themselves. The cellular receptor for the KSHV gH/gL glycoprotein complex, EphA2, and related Eph family receptors are used by several viral and by at least one bacterial pathogen. Recently, it was discovered that even malaria parasites bind this receptor. In our opinion, this kind of convergent evolution warrants a closer examination of EphA2 and of similar receptors to clarify why such a diverse set of pathogens interacts with the same type of protein.
Transmission, epidemiology, and disease
Finally, our group is interested in the biology of the gamma2-herpesviruses in a more general way. The DPZ colony is a unique resource for the collection of virus isolates, not only from rhesus macaques. Sequencing of virus isolates will allow us to analyze the diversity of these viruses and to identify the routes of transmission within the colony. Collaborative studies with the veterinary pathology unit may allow us to discover associations with disease.
Liu S, Großkopf AK, Schlagowski S, Ensser A, Hahn AS; Kaposi's sarcoma-associated herpesvirus glycoprotein K8.1 is critical for infection in a cell-specific manner and functions at the attachment step on keratinocytes.
bioRxiv preprint doi: https://doi.org/10.1101/2023.03.19.533316
Fricke T, Schlagowski S, Liu S, Yang X, Fiebig U, Kaul A, Ensser A, Hahn AS. Comparison of a Genotype 1 and a Genotype 2 Macaque Foamy Virus env Gene Indicates Distinct Infectivity and Cell-Cell Fusion but Similar Tropism and Restriction of Cell Entry by Interferon-Induced Transmembrane Proteins.
Viruses. 2023 Jan 17;15(2):262. doi: 10.3390/v15020262.
Fricke T, Großkopf AK, Ensser A, Backovic M, Hahn AS; Antibodies Targeting KSHV gH/gL Reveal Distinct Neutralization Mechanisms. Viruses, 2022, 14 (3), 541
Hörnich BF, Großkopf AK, Dcosta CJ, Schlagowski S, Hahn AS; Interferon-Induced Transmembrane Proteins Inhibit Infection by the Kaposi’s Sarcoma-Associated Herpesvirus and the Related Rhesus Monkey Rhadinovirus in a Cell-Specific Manner. mBio. 2021 Dec 21;12(6):e0211321. doi: 10.1128/mBio.02113-21.
Großkopf AK, Schlagowski SC, Ensser A, Desrosiers RC, Hahn AS; Plxdc family members are novel receptors for the rhesus monkey rhadinovirus (RRV). PLoS Pathogens. 2021 Mar 03; 17(3): e1008979. doi: 10.1371/journal.ppat.1008979.
Hörnich BF, Großkopf AK, Schlagowski S, Tenbusch M, Kleine-Weber H, Neipel F, Stahl-Hennig C, Hahn AS; SARS-CoV-2 and SARS-CoV spike-mediated cell-cell fusion differ in the requirements for receptor expression and proteolytic activation. Journal of Virology. 2021 Feb 19;JVI.00002-21. doi: 10.1128/JVI.00002-21.
Ensser A, Yasuda K, Lauer W, Desrosiers RC, Hahn AS; Rhesus Monkey Rhadinovirus Isolated from Hemangioma Tissue. Microbiol Resour Announc. 2020 Mar 19;9(12). pii: e01347-19. doi: 10.1128/MRA.01347-19.
Hahn AS, Bischof GF, Großkopf AK, Shin YC, Domingues A, Gonzalez-Nieto L, Rakasz EG, Watkins DI, Ensser A, Martins MA, Desrosiers RC; A Recombinant Rhesus Monkey Deleted of Glycoprotein L Establishes Persistent Infection of Rhesus Macaques and Elicits Conventional T Cell Responses. J Virol. 2020 Jan 6;94(2). pii: e01093-19. doi: 10.1128/JVI.01093-19. Print 2020 Jan 6.
Großkopf AK, Schlagowski S, Hörnich BF, Fricke T, Desrosiers RC, Hahn AS; EphA7 functions as receptor on BJAB cells for cell-to-cell transmission of the Kaposi's sarcoma-associated herpesvirus (KSHV) and for cell-free infection by the related rhesus monkey rhadinovirus (RRV). J Virol. 2019 May 22. pii: JVI.00064-19. doi: 10.1128/JVI.00064-19.
Ensser A, Großkopf AK, Mätz-Rensing K, Roos C, Hahn AS; Isolation and sequence analysis of a novel rhesus macaque foamy virus isolate with a serotype-1-like env. Arch Virol. 2018 Sep;163(9):2507-2512. doi: 10.1007/s00705-018-3892-9.
Großkopf AK, Ensser A, Neipel F, Jungnickl D, Schlagowski S, Desrosiers RC, Hahn AS; A Conserved Eph Family Receptor-Binding Motif on the gH/gL Complex of Kaposi’s Sarcoma-Associated Herpesvirus and Rhesus Monkey Rhadinovirus. PLoS Pathogens, 2018, 2018 Feb 12;14(2):e1006912. doi: 10.1371
Hahn AS, Großkopf AK, Jungnickl D, Scholz B, Ensser A; Viral Fgarat Homolog ORF75 Of Rhesus Monkey Rhadinovirus Effects Proteasomal Degradation Of The ND10 Components SP100 And PML. Journal of Virology, 2016 Aug 12;90(17):8013-28.
Hahn AS, Desrosiers RC; Binding of the Kaposi's Sarcoma-Associated Herpesvirus to the Ephrin Binding Surface of the EphA2 Receptor and its Inhibition by a Small Molecule. Journal of Virology, 2014, 88(16):8724.
Hahn AS, Desrosiers RC; Rhesus monkey rhadinovirus uses Eph family receptors for entry into B cells and endothelial cells but not fibroblasts. PLoS Pathogens, 2013 May 16;9(5):e1003360.
Hahn AS, Kaufmann JK, Wies E, Naschberger E, Panteleev-Ivlev J, Schmidt K, Holzer A, Schmidt M, Chen J, König S, Ensser A, Myoung J, Brockmeyer NH, Stürzl M, Fleckenstein B, Neipel F; The ephrin receptor tyrosine kinase A2 is a cellular receptor for Kaposi’s sarcoma–associated herpesvirus. Nature Medicine, 2012 Jun;18(6):961-6.
Wies E*, Hahn AS*, Schmidt K, Viebahn C, Rohland N, Lux A, Schellhorn T, Holzer A, Jung JU, Neipel F; The Kaposi’s sarcoma-associated herpesvirus encoded vIRF-3 inhibits cellular IRF-5. Journal of Biological Chemistry, 2009 Mar 27;284(13):8525-38. * shared first authors
Hahn A, Birkmann A, Wies E, Dorer D, Mahr K, Stürzl M, Titgemeier F, Neipel F; Kaposi’s Sarcoma Associated Herpesvirus gH/gL: Glycoprotein Export and Interaction with Cellular Receptors. Journal of Virology, 2009 Jan 1;83(1):396-407.