AEGiS-11IAC: Neonatal inoculation of pigtailed macaques (M. nemestrina) with HIV-1.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

Neonatal inoculation of pigtailed macaques (M. nemestrina) with HIV-1.

Int Conf AIDS 1996 Jul 7-12; 11:5 (abstract no. We.A.144)
Bosch ML, Schmidt A, Agy M, Florey MJ, Anderson D, Numankadic S, Herz A, Robertson M, Morton W; Wash. Reg. Primate Res. Center, University of Washington, Seattle, WA, USA. Fax: +1 (206) 685 0305. E-mail: ASCHMIDT@bart.rprc.washington.edu.

OBJECTIVE: To establish infection with HIV-1 in neonatal macaques, with the purpose to create a monkey model in which HIV-1 viral pathogenesis can be studied directly.

METHODS: We have infected pigtailed macaques with HIV-1 at birth. Four animals were infected orally (2 ml of tissue culture supernatant containing HIV-1LAI and HIV-1NL4-3), two were infected i.v. and two were inoculated orally with heat inactivated virus. At present we have data on the orally infected monkeys only.

RESULTS: All four monkeys inoculated orally with infectious HIV-1 showed a dramatic drop in white blood cells, including lymphocytes, in the first week of life (67% loss), compared to on average 8% loss in historical controls. These animals were retarded in growth, losing on average 20 grams over the first four weeks of life, compared to an average of 100 grams weight gain in controls. Three of these four animals recovered to normal blood cell counts and low normal weight increase. HIV-1 could be isolated from the PBMC of one of these animals at day 50. The same sample was positive for HIV-1 viral DNA by PCR. The fourth animal did not recover, suffered from an episode of bacterial scepticemia, and was killed at 67 days of age. Pathology of this animal showed an abnormally small thymus, and small lymph nodes, as well as lymphocytic infiltrates in most tissues examined (liver, heart, kidney, etc.). No evidence for HIV-1 DNA could be detected in the tissue of this animal by solution-based PCR or in situ PCR. None of the animals generated detectable amounts of anti-HIV-1 antibodies or cytotoxic T lymphocytes.

CONCLUSIONS: M. nemestrina inoculated orally with HIV-1 at birth suffered dramatic loss of white blood cells during the first week of life, and failed to gain weight during the first four weeks of life. Limited evidence for viral infection was found by virus culture at one time point in one animal only. Further study into a role for HIV-1 in the pathogenesis specifically in the first week of life is needed.

Keywords: AEGIS, HIV-1, Macaca, Macaca nemestrina, Vaccination, T-Lymphocytes, Cytotoxic, Polymerase Chain Reaction, Animal, ICA11

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WeA144