HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

A herpes simplex virus-derived replicative vector expressing LIF limits experimental demyelinating disease and modulates autoimmunity.

Abstract
Herpes simplex virus type 1 (HSV-1) has properties that can be exploited for the development of gene therapy vectors. The neurotropism of HSV enables delivery of therapeutic genes to the nervous system. Using a bacterial artificial chromosome (BAC), we constructed an HSV-1(17(+))-based replicative vector deleted of the neurovirulence gene γ134.5, and expressing leukemia inhibitory factor (LIF) as a transgene for treatment of experimental autoimmune encephalomyelitis (EAE). EAE is an inducible T-cell mediated autoimmune disease of the central nervous system (CNS) and is used as an animal model for multiple sclerosis. Demyelination and inflammation are hallmarks of both diseases. LIF is a cytokine that has the potential to limit demyelination and oligodendrocyte loss in CNS autoimmune diseases and to affect the T-cell mediated autoimmune response. In this study SJL/J mice, induced for EAE, were treated with a HSV-LIF vector intracranially and the subsequent changes in disease parameters and immune responses during the acute disease were investigated. Replicating HSV-LIF and its DNA were detected in the CNS during the acute infection, and the vector spread to the spinal cord but was non-virulent. The HSV-LIF significantly ameliorated the EAE and contributed to a higher number of oligodendrocytes in the brains when compared to untreated mice. The HSV-LIF therapy also induced favorable changes in the expression of immunoregulatory cytokines and T-cell population markers in the CNS during the acute disease. These data suggest that BAC-derived HSV vectors are suitable for gene therapy of CNS disease and can be used to test the therapeutic potential of immunomodulatory factors for treatment of EAE.
AuthorsMichaela Nygårdas, Henrik Paavilainen, Nadine Müther, Claus-Henning Nagel, Matias Röyttä, Beate Sodeik, Veijo Hukkanen
JournalPloS one (PLoS One) Vol. 8 Issue 5 Pg. e64200 ( 2013) ISSN: 1932-6203 [Electronic] United States
PMID23700462 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Cytokines
  • Immunologic Factors
  • Leukemia Inhibitory Factor
  • RNA, Messenger
Topics
  • Animals
  • Autoimmunity
  • Brain (immunology, metabolism, virology)
  • Chlorocebus aethiops
  • Cytokines (genetics, metabolism)
  • Encephalomyelitis, Autoimmune, Experimental (immunology, therapy)
  • Female
  • Genetic Therapy
  • Genetic Vectors
  • Immunologic Factors (biosynthesis, genetics)
  • Immunomodulation
  • Leukemia Inhibitory Factor (biosynthesis, genetics)
  • Mice
  • Myelin Sheath (pathology)
  • Oligodendroglia (immunology)
  • RNA, Messenger (genetics, metabolism)
  • Simplexvirus (genetics)
  • Spinal Cord (immunology, metabolism, virology)
  • Vero Cells
  • Virus Replication

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: