Table 1.
Animal Groups | ID | Primate Center | Start of Natalizumab (dpi) | BrdU Administration (dpi) | Survival (dpi) | Cardiac Pathology | ||
---|---|---|---|---|---|---|---|---|
Inflammation | Fibrosis | Cardiomyocyte Degeneration | ||||||
Early untreated n=3 | A1 | TNPRC | — | 6, 20 | 22 | NSF | NSF | NSF |
A2 | TNPRC | — | 6, 20 | 22 | NSF | NSF | NSF | |
A3 | TNRPC | — | 22 | 22 | Mild | Mild | NSF | |
Early natalizumab n=6 | A4 | NERPC | 0 | 6, 20 | 21 | NSF | NSF | NSF |
A5 | NERPC | 0 | 6, 20 | 21 | NSF | NSF | NSF | |
A6 | BIOQUAL | 0 | 6, 20 | 21 | NSF | NSF | NSF | |
A7 | BIOQUAL | 0 | 6, 20 | 21 | NSF | NSF | NSF | |
A8 | BIOQUAL | 0 | 6, 20 | 21 | Mild | Mild | Mild | |
A9 | BIOQUAL | 0 | 6, 20 | 21 | Mild | Mild | NSF | |
Late untreated without cardiac pathology n=3 | A10 | NERPC | — | 49 | 56 | NSF | NSF | NSF |
A11 | NERPC | — | pre, 7, 20, 41, 54 | 56 | NSF | NSF | NSF | |
A12 | NERPC | — | pre, 7, 20, 41, 54 | 55 | Mild | Mild | NSF | |
Late untreated with cardiac pathology n=3 | A13 | TNPRC | — | pre, 7, 26, 55 | 56 | Moderate | Moderate | Mild |
A14 | TNPRC | — | pre, 7, 26, 55 | 65 | Moderate | Moderate | Mild | |
A15 | NERPC | — | 6, 20 | 60 | Severe | Moderate | Moderate | |
Late natalizumab n=4 | A16 | NERPC | 28 | pre, 26, 47 | 49 | Mild | NSF | NSF |
A17 | NERPC | 28 | pre, 26, 47 | 49 | Mild | NSF | NSF | |
A18 | NERPC | 28 | 33, 47 | 49 | Mild | Mild | NSF | |
A19 | NERPC | 28 | 33, 47 | 49 | Moderate | Mild | Mild |
Nineteen animals were used in this study, housed at either the New England Regional Primate Center (NERPC), Tulane National Primate Research Center (TNPRC), or BIOQUAL, as indicated. Six animals began natalizumab treatment at the time of infection at 0 days postinfection (dpi) and were sacrificed at 21 dpi. Three early untreated controls were sacrificed at 22 dpi. Four late natalizumab-treated animals began treatment at 28 dpi and were sacrificed at 49 dpi. Three animals each for late untreated controls without cardiac pathology and with cardiac pathology were sacrificed at 56 to 65 dpi. Pathology was assessed based on the degree of inflammation, fibrosis, and cardiomyocyte degeneration. To investigate whether blocking monocyte/macrophage traffic to the heart decreased SIV-associated cardiac pathology, 10 randomly chosen, ×200 fields of view were chosen and analyzed blindly by a veterinary pathologist. Sections of cardiac tissue were scored based on the degree of change as having no significant findings (NSF), mild, moderate, or severe inflammation, fibrosis, and cardiomyocyte degeneration. BrdU indicates bromodeoxyuridine.