Virus Immunity Pathology (VIP)

The Hirsch lab aims at investigating viral and immunological mechanisms that underlie acute and chronic virus diseases. Viruses cause direct cell damage when taking over the host cell metabolism in order to replicate. Virus replication is faced with innate and adaptive immune responses aiming at limiting the spread of viral damage, but may aggravate acute and chronic pathology and organ failure. The research currently focuses on BK polyomavirus (BKPyV) and JC polyomavirus (JCPyV). BKPyV and JCPyV infect 50% to 95% of the global population, typically without known symptoms or signs, and establish persistent infection in the reno-urinary tract. In immunocompromised people, BKPyV and JCPyV can cause significant pathologies such as nephropathy, hemorrhagic cystitis, cancer, or brain disease. Cell culture-based and immunologic research are used to identify mechanisms that can serve as clinical biomarkers and guide prophylactic or therapeutic interventions.

Publications

Hirsch, H. H. (2023). Polyomaviruses. In L. Goldman & K. A. Cooney (Eds.), Goldman-Cecil Medicine (27th ed., Vol. 2, pp. 2227-2233). Elsevier. https://www.asia.elsevierhealth.com/9780323930383.html

DeCaprio, J. A., Imperiale, M. J., & Hirsch, H. H. (2021). Polyomaviridae. In P. M. Howley & D. M. Knipe (Eds.), Fields Virology (7 ed., Vol. 2: DNA Viruses, pp. 1-44). Lippincott Williams & Wilkins. https://shop.lww.com/Fields-Virology--DNA-Viruses/p/9781975112578

Leuzinger, K., & Hirsch, H. H. (2023). Human polyomaviruses. In K. C. Carroll & M. A. Pfaller (Eds.), Manual of Clinical Microbiology (13th ed., pp. 2093-2130). ASM Press. https://www.clinmicronow.org/doi/10.1128/9781683670438.MCM.ch109

Kotton, C. N., Kamar, N., Wojciechowski, D., Eder, M., Hopfer, H., Randhawa, P., Sester, M., Comoli, P., Tedesco Silva, H., Knoll, G., Brennan, D. C., Trofe-Clark, J., Pape, L., Axelrod, D., Kiberd, B., Wong, G., Hirsch, H. H., & Transplantation Society International BK Polyomavirus Consensus Group. (2024). The Second International Consensus Guidelines on the Management of BK Polyomavirus in Kidney Transplantation. Transplantation, 108(9), 1834-1866. https://doi.org/10.1097/TP.0000000000004976

Kaur, A., Wilhelm, M., Wilk, S., & Hirsch, H. H. (2019). BK polyomavirus-specific antibody and T-cell responses in kidney transplantation: update. Curr Opin Infect Dis, 32(6), 575-583. https://doi.org/10.1097/qco.0000000000000602

Cesaro, S., Dalianis, T., Hanssen Rinaldo, C., Koskenvuo, M., Pegoraro, A., Einsele, H., Cordonnier, C., Hirsch, H. H., & ECIL-6 Group. (2018). ECIL guidelines for the prevention, diagnosis and treatment of BK polyomavirus-associated haemorrhagic cystitis in haematopoietic stem cell transplant recipients. J Antimicrob Chemother, 73(1), 12-21. https://doi.org/10.1093/jac/dkx324

Hirsch, H. H., Kaufmann, G., Sendi, P., & Battegay, M. (2004). Immune reconstitution in HIV infected patients. Clin Infect Dis, 38(8), 1159-1166. https://doi.org/10.1086/383034

Durairaj, J., Follonier, O. M., Leuzinger, K., Alexander, L. T., Wilhelm, M., Pereira, J., Hillenbrand, C. A., Weissbach, F. H., Schwede, T., & Hirsch, H. H. (2024). Structural implications of BK polyomavirus sequence variations in the major viral capsid protein Vp1 and large T-antigen: a computational study. mSphere, 9(4), e0079923. https://doi.org/10.1128/msphere.00799-23

Leuzinger, K., Kaur, A., Wilhelm, M., Frank, K., Hillenbrand, C. A., Weissbach, F. H., & Hirsch, H. H. (2023). Molecular Characterization of BK Polyomavirus Replication in Allogeneic Hematopoietic Cell Transplantation. J Infect Dis, 227(7), 888-900. https://doi.org/10.1093/infdis/jiac450

Weissbach, F. H., Follonier, O. M., Schmid, S., Leuzinger, K., Schmid, M., & Hirsch, H. H. (2024). Single-cell RNA-sequencing of BK polyomavirus replication in primary human renal proximal tubular epithelial cells identifies specific transcriptome signatures and a novel mitochondrial stress pattern. J Virol, 98(12), e0138224. https://doi.org/10.1128/jvi.01382-24

Wilhelm, M., Kaur, A., Geng, A., Wernli, M., & Hirsch, H. H. (2025). Donor Variability and PD-1 Expression Limit BK Polyomavirus-specific T-cell Function and Therapy. Transplantation, 109(9), 1526-1539. https://doi.org/10.1097/TP.0000000000005399

Hillenbrand, C. A., Akbari Bani, D., Follonier, O., Kaur, A., Weissbach, F. H., Wernli, M., Wilhelm, M., Leuzinger, K., Binet, I., Bochud, P. Y., Golshayan, D., Hirzel, C., Manuel, O., Mueller, N. J., Schaub, S., Schachtner, T., Van Delden, C., Hirsch, H. H., & Swiss Transplant Cohort Study. (2025). BK polyomavirus serotype-specific antibody responses in blood donors and kidney transplant recipients with and without new-onset BK polyomavirus-DNAemia: A Swiss Transplant Cohort Study. Am J Transplant, 25(5), 985-1001. https://doi.org/10.1016/j.ajt.2024.11.019

Manzetti, J., Weissbach, F. H., Graf, F. E., Unterstab, G., Wernli, M., Hopfer, H., Drachenberg, C. B., Rinaldo, C. H., & Hirsch, H. H. (2020). BK Polyomavirus Evades Innate Immune Sensing by Disrupting the Mitochondrial Network and Promotes Mitophagy. iScience, 23(7), 101257. https://doi.org/10.1016/j.isci.2020.101257

Meier, R. P. H., Muller, Y. D., Dietrich, P. Y., Tille, J. C., Nikolaev, S., Sartori, A., Labidi-Galy, I., Ernandez, T., Kaur, A., Hirsch, H. H., McKee, T. A., Toso, C., Villard, J., & Berney, T. (2021). Immunologic Clearance of a BK Virus-associated Metastatic Renal Allograft Carcinoma. Transplantation, 105(2), 423-429. https://doi.org/10.1097/tp.0000000000003193

Müller, D. C., Rämö, M., Naegele, K., Ribi, S., Wetterauer, C., Perrina, V., Quagliata, L., Vlajnic, T., Ruiz, C., Balitzki, B., Grobholz, R., Gosert, R., Ajuh, E. T., Hirsch, H. H., Bubendorf, L., & Rentsch, C. A. (2018). Donor-derived, metastatic urothelial cancer after kidney transplantation associated with a potentially oncogenic BK polyomavirus. J Pathol, 244(3), 265-270. https://doi.org/10.1002/path.5012