SARS Coronavirus Fusion Peptide-Derived Sequence Suppresses Collagen-Induced Arthritis in DBA/1J Mice

Shen, Zu T.; Sigalov, Alexander B.

In summary, histopathology examination showed greatly reduced joint inflammation and damage in MG11-treated mice compared with the vehicle-treated mice or mice treated with MG11-2G suggesting a specific protective effect of the MG11 peptide. No significant difference was observed in the histopathological analysis of the joint limbs in mice treated with free MG11 (25 mg/kg/day) or sHDL-bound MG11 (2.5 mg/kg/day). As mentioned above, the prolonged half-life of the peptide incorporated into the HDL particle is probably one of the reasons why sHDL-bound MG11 at a dose of 2.5 mg/kg/day is similarly effective to free MG11 at a dose of 25 mg/kg/day. The SARS-CoV FP sequence MG11 reduces cytokine serum levels in mice with CIA. To investigate potential mechanisms underlying the effect of MG11, we examined the serum levels of different cytokines on day 38 using a quantitative Multiplex ELISA array. In mice treated with free MG11 at 25 mg/kg/day or sHDL-bound MG11 at 2.5 mg/kg/day, the cytokine levels were significantly lower than in the vehicle-treated mice or those treated with MG11-2 G at 25 mg/kg/day (Fig. 5) . Interestingly, treatment with MG11 reduced the serum level of macrophage colony-stimulating factor (M-CSF) that plays an important proinflammatory role in CIA 37 and is known to be produced by a variety of cells 38 including activated T cells 39, 40 . To further elucidate the molecular mechanisms underlying the observed immunomodulatory effect of MG11 in vivo, we used confocal fluorescence microscopy and demonstrated that MG11 inserts into the T cell membrane and colocalizes with TCR in T cells in vitro (Supplemental Fig. 1) .