The progressive multifocal leukoencephalopathy (PML) onset after biological drugs treatment has raised concerns about the safety profile of these agents, but it has also provided a window into the pathogenesis of PML, a fatal demyelinating disease caused by the human Polyomavirus JC (JCV). Although the hypothesis that immune-deficiency is a predisposing factor for PML, there are many unsolved issues including the pathogenetic mechanisms related to the interaction of JCV infection/reactivation with the host. Probably these mechanisms are based on a reduced immune-surveillance of the central nervous system and on a latent JCV infection in lymphoid cells of peripheral circulation. In fact, despite its lytic capability in oligodendrocytes, JCV can persist in a variety of cell types, including CD34+ and B cells. Therefore, it is probable that lymphoid specific transcription factors, such as Spi-B, regulate JCV gene expression. Spi-B is involved in B cells differentiation and it is expressed in mature B cells. Moreover Spi-B binds adjacent to TATA box in the regulatory region of the PML-associated JCV Mad-1 and Mad-4 but not the non-pathogenic archetype CY. Importantly, in our research we found mutations in active Spi-B-binding sites adjacent to the TATA box of archetype-like viruses in several samples collected from different autoimmune diseases patients treated with monoclonal antibodies, suggesting that these mutations are supported during dissemination in the host. Finally, the correlations of JCV genomic analysis and Spi-B gene expression with the patients’ immunological profiles might be used in the future as useful genomic and immunological biomarkers in clinical practice.

Role of the biological drugs on JCV reactivation and PML pathogenesis / Pietropaolo, Valeria Antonietta. - In: JOURNAL OF NEUROVIROLOGY. - ISSN 1355-0284. - ELETTRONICO. - 19:(2013), pp. 302-302. (Intervento presentato al convegno 5th International Conference on Polyomaviruses and Human Diseases - Basic and Clinical Perspectives tenutosi a Stresa, ITALY nel MAY 09-11, 2013) [10.1007/s13365-013-0171-0].

Role of the biological drugs on JCV reactivation and PML pathogenesis

PIETROPAOLO, Valeria Antonietta
2013

Abstract

The progressive multifocal leukoencephalopathy (PML) onset after biological drugs treatment has raised concerns about the safety profile of these agents, but it has also provided a window into the pathogenesis of PML, a fatal demyelinating disease caused by the human Polyomavirus JC (JCV). Although the hypothesis that immune-deficiency is a predisposing factor for PML, there are many unsolved issues including the pathogenetic mechanisms related to the interaction of JCV infection/reactivation with the host. Probably these mechanisms are based on a reduced immune-surveillance of the central nervous system and on a latent JCV infection in lymphoid cells of peripheral circulation. In fact, despite its lytic capability in oligodendrocytes, JCV can persist in a variety of cell types, including CD34+ and B cells. Therefore, it is probable that lymphoid specific transcription factors, such as Spi-B, regulate JCV gene expression. Spi-B is involved in B cells differentiation and it is expressed in mature B cells. Moreover Spi-B binds adjacent to TATA box in the regulatory region of the PML-associated JCV Mad-1 and Mad-4 but not the non-pathogenic archetype CY. Importantly, in our research we found mutations in active Spi-B-binding sites adjacent to the TATA box of archetype-like viruses in several samples collected from different autoimmune diseases patients treated with monoclonal antibodies, suggesting that these mutations are supported during dissemination in the host. Finally, the correlations of JCV genomic analysis and Spi-B gene expression with the patients’ immunological profiles might be used in the future as useful genomic and immunological biomarkers in clinical practice.
2013
5th International Conference on Polyomaviruses and Human Diseases - Basic and Clinical Perspectives
04 Pubblicazione in atti di convegno::04c Atto di convegno in rivista
Role of the biological drugs on JCV reactivation and PML pathogenesis / Pietropaolo, Valeria Antonietta. - In: JOURNAL OF NEUROVIROLOGY. - ISSN 1355-0284. - ELETTRONICO. - 19:(2013), pp. 302-302. (Intervento presentato al convegno 5th International Conference on Polyomaviruses and Human Diseases - Basic and Clinical Perspectives tenutosi a Stresa, ITALY nel MAY 09-11, 2013) [10.1007/s13365-013-0171-0].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/517709
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