TY - JOUR
T1 - The murine gammaherpesvirus-68 chemokine-binding protein M3 inhibits experimental autoimmune encephalomyelitis
AU - Millward, Jason M
AU - Holst, Peter J
AU - Høgh-Petersen, Mette
AU - Thomsen, Allan R
AU - Christensen, Jan P
AU - Owens, Trevor
N1 - Keywords: Adenoviridae; Animals; Cell Line; Cell Migration Inhibition; Chemokines; Encephalomyelitis, Autoimmune, Experimental; Female; Gene Therapy; Gene Transfer Techniques; Genetic Vectors; Humans; Mice; Mice, Inbred C57BL; Protein Binding; Rhadinovirus; Severity of Illness Index; Treatment Outcome; Viral Proteins
PY - 2010/7
Y1 - 2010/7
N2 - 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.
AB - 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.
U2 - 10.1016/j.jneuroim.2010.05.005
DO - 10.1016/j.jneuroim.2010.05.005
M3 - Journal article
C2 - 20537410
SN - 0165-5728
VL - 224
SP - 45
EP - 50
JO - Journal of Neuroimmunology
JF - Journal of Neuroimmunology
IS - 1-2
ER -