Human iPS cell-derived astrocytes support efficient replication of progressive multifocal leukoencephalopathy-type JC polyomavirus

Abstract

JC polyomavirus (JCPyV) causes progressive multifocal leukoencephalopathy (PML), a demyelinating disease of the central nervous system, in immunocompromised patients. Although PML used to be rare, recently the incidence of PML has risen due to an increase in immunosuppressive therapy. An in vitro JCPyV infection system could be used for anti-drug screening and investigation of tropism changes, but study of JCPyV in vitro has been limited due to the difficulty of efficiently propagating the virus in cultured cells. PML-type JCPyV efficiently propagates in primary human fetal and progenitor cell-derived astrocytes, but the preparation of cells from human fetuses is associated with severe ethical problems. In this study, human iPS cell-derived astrocytes were exposed to PML-type JCPyV. Infection, replication, and VP1 and T antigens of JCPyV were detected and confirmed in this culture. The non-coding control region (NCCR) of M1-IMRb was conserved in infected cells without point mutations. In addition, PML-type JCPyV genomic DNA in infected cells was detected as a single band of approximately 5.1 kbp, with no deletions. This is the first demonstration that human iPS cell-derived astrocytes efficiently support replication of PML-type JCPyV without production of defective interfering particles. These findings indicated that a culture system using human iPS cell-derived astrocyte would be useful for studies of PML, especially for screening anti-JCPyV drugs.

Keywords: Astrocyte; JC polyomavirus; M1-IMRb; PML; iPS cell.