Direct inoculation of simian immunodeficiency virus from sooty mangabeys in black mangabeys (Lophocebus aterrimus): first evidence of AIDS in a heterologous African species and different pathologic outcomes of experimental infection.

A unique opportunity for the study of the role of serial passage and cross-species transmission was offered by a series of experiments carried out at the Tulane National Primate Research Center in 1990. To develop an animal model for leprosy, three black mangabeys (BkMs) (Lophocebus aterrimus) were inoculated with lepromatous tissue that had been serially passaged in four sooty mangabeys (SMs) (Cercocebus atys). All three BkMs became infected with simian immunodeficiency virus from SMs (SIVsm) by day 30 postinoculation (p.i.) with lepromatous tissue. One (BkMG140) died 2 years p.i. from causes unrelated to SIV, one (BkMG139) survived for 10 years, whereas the third (BkMG138) was euthanized with AIDS after 5 years. Histopathology revealed a high number of giant cells in tissues from BkMG138, but no SIV-related lesions were found in the remaining two BkMs. Four-color immunofluorescence revealed high levels of SIVsm associated with both giant cells and T lymphocytes in BkMG138 and no detectable SIV in the remaining two. Serum viral load (VL) showed a significant increase (>1 log) during the late stage of the disease in BkMG138, as opposed to a continuous decline in VL in the remaining two BkMs. With the progression to AIDS, neopterin levels increased in BkMG138. This study took on new significance when phylogenetic analysis unexpectedly showed that all four serially inoculated SMs were infected with different SIVsm lineages prior to the beginning of the experiment. Furthermore, the strain infecting the BkMs originated from the last SM in the series. Therefore, the virus infecting BkMs has not been serially passaged. In conclusion, we present the first compelling evidence that direct cross-species transmission of SIV may induce AIDS in heterologous African nonhuman primate (NHP) species. The results showed that cross-species-transmitted SIVsm was well controlled in two of three BkMs for 2 and 10 years, respectively. Finally, this case of AIDS in an African monkey suggests that the dogma of SIV nonpathogenicity in African NHP hosts should be reconsidered.

Detection of IgA anti-PGL-I specific antigen to Mycobacterium leprae in mangabey monkeys inoculated with M. leprae.

Using sera from 4 pairs of mangabey monkeys inoculated with titrated doses of Mycobacterium leprae we demonstrated that IgA antibodies against M. leprae specific PGL-I antigen were present in 75% of inoculated monkey's sera. High IgA antibody was detected in 50% (3/6) of infected animals and all three developed lepromatous leprosy (LL). Antibody titers correlated with PGL-I antigen in serum. The highest IgA peak appeared late and corresponded to the beginning of treatment, and in two of them appeared shortly after or corresponded with neurological damage. Low IgA response was found in the other 3 monkeys (50%-3/6), two of which developed indeterminate leprosy (I) and the other one LL. Low IgA levels appeared late after IgG and IgM, and shortly after neurologic signs. Both I monkeys were negative for PGL-I in serum. The remaining 2 monkeys (25%-2/8) did not show an IgA response; one of them developed LL but the disease regressed to I. IgM seemed to correspond to the appearance of PGL-I in serum. The other animal did not develop clinical symptoms of leprosy, and PGL-I in serum was negative. Although there was no clear relation between the development of anti-PGL-I IgA and experimental leprosy, the finding of a high IgA response in some animals suggests that further studies are needed to evaluate the role of antigen-specific IgA in the disease process.

[Peripheral nerve lesions of experimental leprosy in monkeys. VII. Intrafascicular-edema and small blood vessels].

Histopathological findings of intrafascicular-edema found in n. ulnaris running at forearm, palmside of hand and fingers of rhesus monkey 8664 and african green monkey 8175 were studied by semithin section method. These two monkeys were inoculated with leprosy bacilli from lepromata of mangabey monkey A022. The mangabey monkey A022 had been experimental leprosy after inoculum of the leprosy bacilli from lepromata of the mangabey monkey A015-natural infection. Period between date of inoculum and sacrifice of the rhesus monkey 8664 was about 2 years, and the african green monkey 8175 was about 5 years. Results found were: 1. Intrafascicular-edema found in n. ulnaris running at forearm, palmside of hand and fingers was remarkable at some of peculiar anatomical areas where were put on mechanical pressure. 2. The intrafascicular-edema inside many fascicles was remarkable around the small blood vessels. 3. Obsruction of the small blood vessels and congestion of blood stream at surrounded of the intrafascicular-edema with fibrous elements and cellular elements were observed inside some of fascicles. 4. Bundles of peripheral nerve fibers inside some of fascicles were pressed by the intrafascicular-edema, and the fibrous elements, especially collagen fibers, were increased around the pressed bundles of nerve fibers and each nerve fiber inside the fascicles. 5. Vacuolar degeneration and swelling of axon were observed at some of myelinated nerve fibers. 6. Not only the intrafascicular-edema but also a large amount of intracytoplasmic foamy structures with solid leprosy bacilli were observed inside many fascicles.(ABSTRACT TRUNCATED AT 250 WORDS)