The murine gammaherpesvirus-68 chemokine-binding protein M3 inhibits experimental autoimmune encephalomyelitis.
Chemokines are critical mediators of immune cell entry into the central nervous system (CNS), as occurs in neuroinflammatory disease such as multiple sclerosis. Chemokines are also implicated in the immune response to viral infections. Many viruses encode proteins that mimic or block chemokine actions, in order to evade host immune responses. The murine gammaherpesvirus-68 encodes a chemokine-binding protein called M3, which has unique biochemical features that enable it to bind to and inhibit an unusually broad range of chemokines. We applied a replication-defective adenoviral vector encoding M3 (AdM3) directly to the CNS to evaluate the capacity of this protein to inhibit neuroinflammation using the experimental autoimmune encephalomyelitis (EAE) model. Treatment with the AdM3 vector significantly reduced the clinical severity of EAE, attenuated CNS histopathology, and reduced numbers of immune cells infiltrating the CNS. These results suggest that M3 may represent a novel therapeutic approach to neuroinflammatory disease.
Millward
Jason M
JM
Neuroimmunology Unit, Montreal Neurological Institute, 3801 University Street, Room 111, McGill University, Montreal, Quebec, Canada. jason.millward@charite.de
Holst
Peter J
PJ
Høgh-Petersen
Mette
M
Thomsen
Allan R
AR
Christensen
Jan P
JP
Owens
Trevor
T
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002460:Cell Line; D002464:Cell Migration Inhibition / Q000235:genetics / Q000276:immunology; D018925:Chemokines / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology* / Q000628:therapy* / Q000821:virology; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics / Q000627:therapeutic use; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D011485:Protein Binding / Q000276:immunology; D018144:Rhadinovirus / Q000235:genetics / Q000276:immunology*; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014764:Viral Proteins / Q000235:genetics / Q000627:therapeutic use*
D018925:Chemokines; C118862:M3 protein, Murine gammaherpesvirus; D014764:Viral Proteins