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Session 65 Poster Abstracts
Emerging Issues in Monkey Pathogenesis Models
Thursday, 1:30 - 3:30 pm
Hall D


325
New Model for the Study of SIV Pathogenesis in Natural Host Species: Infection of Carribean African Green Monkeys with SIVagm.sab
I Pandrea1, C Apetrei1, J Dufour1, N Dillon1, B Poonia1, O Diop2, M Muller-Trutwin3, R Bohm1, P Marx1, A Lackner1, and Ronald Veazey*1
1Tulane Natl Primate Res Ctr, Tulane Univ, Covington, LA, USA; 2Inst Pasteur, Dakar, Senegal; and 3Inst Pasteur, Paris, France

Background:  SIVagm infection is non-pathogenic in African green monkeys. The reasons for the lack of disease following SIV infection in African non-human primates are not known. Extensive studies are hampered by the fact that available models are endangered (sooty mangabeys, mandrills, and chimpanzees) or difficult to import from Africa (African green monkeys). Therefore, we have tested the SIVagm infection in Caribbean African green monkeys to develop a more accessible model for the study of non-pathogenic infection.

Methods:  Plasma from an African green monkey infected with SIVagm.sab92018 strain was used to infect 7 Caribbean African green monkeys and 3 rhesus macaques. Viral loads and immunophenotypic markers were followed during primary infection and during steady-state phase (until day 240 post-infection). Results were compared with available data from African sabaeus and vervets infected with the same virus strain.

Results:  SIVagm.sab92018 replicated to high levels during primary infection of Carribean African green monkeys, and reached 108 to 109 copies/mL at day 10 post-infection. This high peak of plasma viral load was followed by a decrease, with set-points established by day 32 post-infection at 2 x 105 copies/mL. These virological profiles were identical to those previously reported in African sabaeus and vervets using the same viral strain. Comparable high peaks of viral loads were observed in rhesus macaques infected with SIVagm.sab, then the infection was rapidly cleared by day 30 to 42 post-infection CD4 T-cell counts in the blood showed a depletion at the peak of viral load, but this was transitory, reaching normal levels by day 132 post-infection. No significant CD4 depletion was observed in lymph nodes. We also studied the dynamics of CD4 T cells in the intestine. In contrast to the transitory depletion of CD4 T cells in the blood, a significant CD4 T-cell decrease was observed in the intestine of African green monkeys and this was maintained up to day 132 post-infection.

Conclusions:  Due to similarities of virological and immunological parameters of the SIVagm infection in African and Caribbean African green monkeys, the latter seem to be a useful alternative to African monkeys. Caribbean African green monkeys are available in large numbers and at relatively low cost; therefore they represent a valuable tool for the study of SIV infection in their natural host. Moreover, this study demonstrates that, as in macaques, CD4 T-cell depletion occurs preferentially in the gastrointestinal tract. This calls for further investigation of the mechanisms controlling the deleterious effects of SIV in their natural hosts.

Keywords: African green monkeys; SIVagm; animal models