Investigating the nuclear entry mechanism of SV40

Polyomaviruses (PyVs) are DNA viruses that target to and translocate into the host nucleus to cause infection. However, how these steps are accomplished remain largely enigmatic. Included in the PyV family is the human BK PyV responsible for nephropathy and hemorrhagic cystitis, JC PyV that triggers a fatal demyelinating disease called progressive multifocal leukoencephalopathy, and Merkel cell PyV that causes an aggressive skin tumor known as Merkel cell carcinoma (MCC). Because entry of the prototype PyV – simian virus 40 (SV40) – is similar to human PyVs, a coherent understanding of SV40 cell entry will likely identify new strategies to combat PyV-induced human diseases. Accordingly, this proposal seeks to elucidate the nuclear entry mechanism of SV40, focusing on the roles of two distinct nuclear membrane protein complexes that likely participate in this event.