Nuclear Factor I interacting partners in cells permissive and non-permissive to JC Virus replication

Wednesday, October 26, 2011 — Poster Session IV
2:00 p.m. – 4:00 p.m.	Natcher Conference Center	NINDS	VIROL/MICRO-6

Authors

• MW Ferenczy
• AJ Makusky
• EO Major

Abstract

Nuclear Factor I (NFI) transcription factors play a crucial role in neuronal development and are important for the life cycle of viruses including JC virus (JCV). JCV is the etiological agent of the deadly demyelinating disease Progressive Multifocal Leukoencephalopathy (PML). Four different NFI genes, NFI-A, -B, -C, and –X, and various splice variants of each NFI have been identified. The NFI genes are differentially expressed in the cells present in the human brain, which can be derived in vitro through differentiation of human fetal brain progenitors. Progenitor derived-astrocytes are permissive to JCV replication and express high levels of NFI-X, while progenitor derived-neurons are non-permissive and express high levels of NFI-A. Co-immunoprecipitation in combination with mass spectrometry was used to identify proteins that interact with NFI proteins in cell types that are permissive or non-permissive to JCV replication in order to determine mechanisms of viral transcriptional control. Among the proteins found to interact with NFI family members are multiple variants of histones H1 and H2A, proteins involved in chromatin remodeling and DNA repair including members of the TIP60 complex, and components of ribosomes. Further investigation of NFI proteins and their interacting partners may offer targets for future PML therapies.

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