Clinical features and predictive markers of disease progression in cynomolgus monkeys experimentally infected with simian immunodeficiency virus.

OBJECTIVE

To study the pathogenicity of simian immunodeficiency virus (SIVsm) in cynomolgus monkeys in order to establish an animal model for human AIDS.

METHODS

Thirty-three cynomolgus monkeys were monitored for more than 2 years following experimental infection with SIVsm.

RESULTS

All the macaques became SIV-infected, as demonstrated by virus recovery from peripheral blood lymphocytes and by the appearance of viral antibodies. SIVsm was found to be pathogenic, killing 29 out of the 33 monkeys (88%) within 26 months. Clinically, infected monkeys developed lymphadenopathy, splenomegaly, diarrhoea, weight loss, neurological symptoms and a remarkably high incidence (39%) of malignant lymphomas. All lymphomas were high-grade malignant and of B-cell origin. Disease progression was associated with low CD4+ lymphocyte count, involution of initially hyperplastic follicular B-cell areas in lymph nodes, reappearance of viral antigen in serum, loss of anti-Gag antibodies and development of systemic giant cell disease in 55% of the monkeys.

CONCLUSIONS

There are many similarities between SIVsm-induced AIDS in cynomolgus monkeys and human AIDS with regard to clinical, virological, immunological and pathological manifestations.