Neonatal Disease Induced by SIV Infection of the Rhesus Monkey (Macaca mulatta)

Abstract

Seven 72-hr-old Indian origin rhesus monkeys (Macaca mulatto) were inoculated with 10 animal ID₅₀ of SIV/Delta_B670. Nine age-matched animals were used as uninoculated controls. All seven inoculated animals became infected as verified by viral isolation and SIV p26 antigenemia. Five of seven infected animals died within a mean of 31 days (range, 26-41 days), with high levels of antigenemia beginning 1-2 weeks postinoculation (PI) that persisted until death. Absolute lymphocyte numbers were within normal limits in all animals in both groups throughout the study. Inoculated animals that died within a mean of 31 days (short-term survivors) had significantly lower numbers of CD4⁺CD29⁺ (helper/inducer) lymphocytes than did long-term surviving inoculated animals through 3 weeks PI. Numbers of CD4⁺ lymphocytes were no different when controls were compared to all inoculated animals through 4-5 weeks PI. The two inoculated animals surviving 216 and 423 days PI (long-term survivors) did demonstrate declining CD4⁺ cells, but only late in disease. CD8⁺ lymphocytes were significantly lower in short-term survivors when compared to long-term survivors through 5 weeks PI. Antibody production against SIV viral proteins was detected only in the long-term survivors and was similar to results from past studies in juveniles. Clinical signs in the inoculated group were consistent with those seen in past studies on older animals. Persistent bacterial infections, primarily of the GI and respiratory tracts, were seen in the infected group. Aside from the lack of some opportunistic infections such as cytomegalovirus (CMV) and Pneumocystis carinii, necropsy findings were not different when compared to past studies on juvenile animals. We concluded from the experimental results that mean survival time after inoculation in 3-day-old infants is considerably shorter than in animals inoculated as juveniles and that a greater percentage of infected animals demonstrated persistent antigenemia and progressive disease. A decline in the CD4⁺CD29⁺ lymphocyte subset may be a more reliable early indicator of progressive disease and early death than declining CD4⁺ percentages in the SIV-infected neonate.