812 Talk: Contributions of Promyelocytic Leukemia Nuclear Bodies to Lytic BK Polyomavirus Infection

Seminar Details
Friday, February 19, 2021 - 12:00pm to 1:00pm


Megan Procario
Ph.D. Candidate, Microbiology and Immunology, University of Michigan


Polyomaviruses (PyV) are small non-enveloped viruses containing a circular double-stranded DNA genome. This group of viruses can infect a wide range of hosts, including humans. To date, 14 human polyomaviruses (HPyV) have been identified, only five of which are known to cause disease. HPyV disease is usually restricted to individuals with compromised immune systems either due to illness or treatment. In the Imperiale laboratory we study BK polyomavirus (BKPyV), which is known to cause disease in patients following transplants. Following hematopoietic stem cell transplant or bone marrow transplant, patients can develop BK-induced hemorrhagic cystitis (HC), while renal transplant patients are at risk for Polyomavirus-associated Nephropathy (PVAN). Both HC and PVAN are causes of significant morbidity for these patients, with the latter potentially leading to loss of the transplanted kidney.

BKPyV infection persists for the life of the host, with the majority of individuals being infected in early childhood. Following initial infection, BK persists asymptomatically in the urinary tract and can be shed periodically in the urine of the infected individual. We know that the host immune response plays a role in controlling BKPyV disease, but the interplay between this response and BK viral pe

rsistence is unclear. In an effort to improve our understanding, we are focusing on intrinsic host responses to BKPyV infection in our established in vitro model of acute infection. As BKPyV infection is known to disrupt the structure and function of Promyelocytic Leukemia (PML) nuclear bodies, we began there. PML nuclear bodies (PML-NBs) are small, dynamic, subnuclear structures. PML-NBs are involved in a wide range of cellular processes ranging from metabolism to tumor suppression to antiviral responses. PML-NBs exert their antiviral effects directly by sequestering or degrading viral proteins or indirectly by enhancing gene transcription, including interferon stimulated genes. Many viruses have developed mechanisms to evade the effects of PML. These mechanisms include targeting PML for degradation by proteasomes and disruption of PML-NB architecture among others. 

We sought to further explore the role of PML-NBs in BKPyV infection, with the hypothesis that BKPyV infection would be enhanced by the absence of PML-NBs. To test this hypothesis, we generated a PML knock-out cell line and examined lytic BKPyV infection in the absence of PML. Unexpectedly, we discovered that BKPyV virus replication was attenuated in the absence of PML. This finding suggests a positive role for PML in BKPyV replication. Such a role has been previously suggested for other DNA viruses, so understanding the contributions of PML and PML-NBs in BKPyV infection may have broader implications.