In vivo treatment with anti-alpha4 integrin suppresses clinical and pathological evidence of Borna disease virus infection.
Borna disease virus (BDV) infection of the rat brain induces a severe T-lymphocyte mediated inflammatory response that parallels the course of clinical Borna disease. In other models of CNS inflammation, the recruitment of T-lymphocytes from the circulation to sites of inflammation is believed to be directed, in part, by the cellular adhesion molecules alpha4 beta1 integrin (expressed on T-lymphocytes) and its ligand VCAM-1 (expressed on blood brain barrier endothelium). Since BDV-specific T-lymphocytes are known to express the alpha4 beta1 integrin, we examined the effect of in vivo treatment with an anti-alpha4 integrin monoclonal antibody (GG5/3) on the development of BDV-specific encephalitis and Borna disease. Here, we report that the inhibition of alpha4 integrin provided significant clinical benefit in slowing the progression of Borna disease. Antibody treatment greatly reduced the immune cell infiltrates in the CNS of BDV-infected animals, but we found that this inhibition of the immune response did not result in enhanced viral levels.
Rubin
S A
SA
Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Yednock
T A
TA
Carbone
K M
KM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000914:Antibodies, Viral / Q000097:blood; D015703:Antigens, CD / Q000276:immunology*; D001890:Borna Disease / Q000276:immunology* / Q000517:prevention & control / Q000628:therapy; D018792:Encephalitis, Viral / Q000276:immunology / Q000628:therapy; D039441:Integrin alpha4; D008297:Male; D012328:RNA Viruses / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D016201:Receptors, Lymphocyte Homing / Q000276:immunology; D019562:Viral Load; D015430:Weight Gain
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D015703:Antigens, CD; D016201:Receptors, Lymphocyte Homing; D039441:Integrin alpha4