7th International AIDS Conference Florence, Italy — June 16-21, 1991

Int Conf AIDS 1991 Jun 16-21; 7:27 (abstract no. M.A.22)
Nicol I, Boussin F, Vogt G, LeGrand R, Montagnier L, Dormont D; CEA, CRSSA, DSV/DPTE/SSA, Fontenay aux Roses, France

OBJECTIVES: AIDS-like clinical manifestations were observed in an HIV2-ROD infected macaque (33215). This isolate was reinoculated into macaques to obtain an animal model for AIDS disease. Here, we report the in vivo HIV2-ROD genomic variations in the monkey 33215 and the results of the second inoculation.

METHODS: Inoculation: In May 1987, we inoculated 10 macaques with HIV2 ROD. Of these 10 monkeys, 2 presented clinical signs of AIDS: 1 died and 1 was sacrificed (33215). Then, in february 1989, the 8 resting animals were IV reinoculated with supernatant of human cord blood lymphocytes coculture with PBL of the 33215 infected monkey. In addition, one naive monkey was IV inoculated with this supernatant, as a positive control of infection. Serological, Virological and Clinical Follow-up: Western blot, ELISA, neutralizing antibodies, CD4/CD8 ratio, cocultures with human cord blood lymphocytes, and PCR using primers in env and LTR were performed. Partial restriction map of the 33215 isolate and sequencing: DNA was extracted from 33215 infected MOLT4 clone 8 cells, then amplified by PCR using primers in U3 region from 8412 to 9579 and digested by restriction endonucleases. The sequence was obtained by the didcoxy chain termination procedure.

RESULTS: 1) PCR-analysis of HIV2/33215 LTR resulted in a fragment of 870 bp, in contrast to HIV2 ROD which showed a fragment of 1167 bp. Numerous endonucleases digestions demonstrated a U3 deletion in HIV2/33215 which was confirmed by sequencing. This deletion includes partly NEF, "NRE-like", Enhancer sequences, but not the Sp1 sites. 2) After the 2nd inoculation, 8/9 animals were seropositive. Virus isolation could be performed in 6/9 animals. In addition, all the nine animals are found positive using PCR and their CD4+ cells count decreased since the 2nd inoculation. The presence of lymphadenopathy is often observed and skin rash affects chronically one animal. Moreover, another monkey died presenting lymph-nodes abnormalities, massive pulmonary infection and atrophic spleen. The infection control monkey shows a severe cachexia.

CONCLUSIONS: The obtention of a more "virulent form" of the HIV2 ROD after the in vivo passage in a rhesus macaque may provide a clinical immunodeficiency animal model induced by a human retrovirus. This might be an alternative to the HIV1/chimpanzee model for vaccine trials. The appearance of a deletion in U3 might be of importance in regard of the pathogenic power of HIV2, and of the close relationships between the viral negative regulation genes and the pathogenesis.

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