AN IMMUNOVIROLOGICAL STUDY OF CENTRAL-NERVOUS-SYSTEM INVOLVEMENT DURING HIV-1 INFECTION OF CHIMPANZEES

Chimpanzees infected with human immunodeficiency virus type 1 (HIV-1) are used to model acquired immunodeficiency syndrome (AIDS), Since the central nervous system (CNS) is involved in AIDS, we performed an imm unovirological study in 18 chimpanzees inoculated up to 87 months prio r to the study (mean, 45 months) with HIV-1 and 8 uninfected controls. Serum and cerebrospinal fluid (CSF) IgG and albumin levels of infecte d chimpanzees never exceeded those of controls. The CSF/serum albumin ratio was elevated in 1 of 18 infected chimpanzees compared to control s; however, all animals had an elevated ratio indicating a more open b lood-brain barrier relative to humans. The intrathecal IgG production index was elevated in only 1 of 18 infected chimpanzees compared to co ntrols. Identical serum and CSF IgG bands were found by isoelectric fo cusing in 2 of 8 controls and in 1 of 18 infected chimpanzees. None of these bands reacted with recombinant HIV-1 p24gag or gp120env. HIV-1 was isolated from the peripheral blood of 4 of 18 infected chimpanzees but never from the paired CSF samples. Anti-HIV-1 antibody was detect ed by a enzyme-linked immunosorbent assay in 18 of 18 paired serum and CSF samples and by Western blot in 18 of 18 serum and 13 of 18 CSF sa mples from infected chimpanzees without a difference in pattern. Polym erase chain reaction analysis on brain tissue of one animal was negati ve for HIV-1 sequences. Our results demonstrate that, unlike human inf ection, chimpanzees inoculated with HIV-1 show no evidence of isolatab le virus in the CSF and no evidence of intrathecal anti-HIV-1 antibody synthesis up to several years after experimental infection. The Lack of CNS involvement may contribute to the delay or suppression of clini cal disease in infected chimpanzees.