[2][3] A component of mouse leukemia extract capable of causing tumors, particularly in the parotid gland, in newborn mice was reported by Ludwik Gross in 1953[4] and identified as a virus by Sarah Stewart and Bernice Eddy at the National Cancer Institute, after whom it was once called "SE polyoma".

[5][6][7] Stewart and Eddy would go on to study related polyomaviruses such as SV40 that infect primates, including humans.

[12] Like other members of the polyomavirus family, MPyV has an unenveloped icosahedral (T=7) viral capsid around 45 nanometers in diameter.

[1][19] The functions of VP2 and VP3 are less well understood, but at least VP2 has been reported to be exposed upon endocytosis of the viral particle and may be involved in releasing the virus from the endoplasmic reticulum.

[21][22] Unlike many viruses that enter the cell through endocytosis, polyomaviruses penetrate the cell membrane and enter the cytosol from the late endoplasmic reticulum rather than from endosomes, although conformational changes in response to low pH in endolysosomes have been hypothesized as critical steps in the process.

[24] It is not known whether entry into the cytosol is obligatory for MPyV infection or whether the particle could enter the cell nucleus directly from the ER.

Capsid proteins, produced in the cytoplasm of the host cell, enter the nucleus as assembled capsomers consisting of pentameric VP1 associated with VP2 or VP3.

Once inside the nucleus they assemble into mature capsids containing a copy of the viral genome, although the exact mechanism of encapsidation is not well understood.

[26] Filamentous or tubular structures representing polymerized VP1 have been observed in the nuclei of infected cells as intermediates in the assembly process from which mature virions are produced.