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Interferon‐alpha and –beta restrict Polyomavirus JC (JCV) replication in primary human fetal glial cells (PHFG): Implications for progressive multifocal leukoencephalopathy (PML) therapy
Author(s) -
Verma Saguna,
Co Juliene K.,
Sumibcay Laarni,
Gurjav Ulziijargal,
Nerurkar Vivek R.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a65-d
Subject(s) - progressive multifocal leukoencephalopathy , demyelinating disease , jc virus , virology , viral replication , interferon , immunology , biology , immune system , virus , antigen , medicine , multiple sclerosis
PML, a fatal demyelinating disease of the central nervous system is caused by the ubiquitous JCV. Currently immune reconstitution by HAART is the most effective therapy for AIDS‐PML patients. Although HAART controls HIV replication, it does not inhibit JCV replication, and 50% of patients do not respond to HAART. We previously demonstrated induction of interferon (IFN) antiviral response by JCV in PHFG cells. The objective of this study was to analyze viral events critical to induce ISG, and to assess the effects of IFN‐α and –β on JCV replication. Quantitative analysis of ISG and JCV T antigen RNA by real‐time RT‐PCR, and qualitative analysis of JCV T antigen protein expression were used to measure antiviral effect of IFN in JCV‐infected PHFG cells. Treatment with both, IFN‐ α and –β resulted in significant induction of key ISG, and productive virus replication was essential for the induction of ISG. Moreover, JCV replication was significantly inhibited in presence of IFN‐ α and –β. Effect of IFN on JCV replication was reversed in the presence of neutralizing anti‐IFN antibody. Our in vitro data demonstrating direct antiviral effect of IFN on JCV, suggests that IFN‐ α and –β can be used as an adjunct therapy to manage PML patients. Since IFN cannot cross the blood‐brain barrier to achieve its direct antiviral effect, intrathecal administration of IFN is warranted.