AEGiS-13IAC: Lentiviral infection impact on macaque hematopoiesis.

13th International AIDS Conference

Durban, South Africa - July 9-July 14, 2000

Lentiviral infection impact on macaque hematopoiesis.

Int Conf AIDS 2000 Jul 9-14; 13:(abstract no. MoOrA173)

Thiebot H, Vaslin B, Louache F, De Revel T, Neiloez O, Larghero J, Dormont D, Le Grand R
H. Thiebot, 6068 Avenue De La Division Leclerc, Fontenay Alux Roses 92265 BP6, France, Tel.: +33 1 014 654 9463, Fax: +33 1 014 654 7726, E-mail: bossuet@dsvidf.cen.fr

OBJECTIVES: The aim of this study is to determine, in the model of macaques infected with a pathogenic simian/human chimeric virus (SHIV), the clonogenic capacity of bone marrow primitives (long term cultures-initiating cells or LTC-IC)) and slightly differentiated hematopoietics progenitor cells (cells forming colony or CFC). Materials and

METHODS: Three groups of macaques are inoculated with 50 MID50 of a pathogenic SHIV89.P stock. This chimera expressed the env gene of the primary HIV-1 89.6 isolate in a SIV mac 239 backgroup. During primary infection, animals were treated with a placebo or with the combination of AZT (4.5 mg/kg), 3TC (2.5 mg/kg) and indinavir (20 mg/kg) twice a day until day 28 p.i. Treatement was initiated at 4 h and 72 h p.i. Hematological, virological and immunological parameters were followed during one year. The virus impact on hematopoietic progenitors was estimated, using two tests of clonogenicity, for detect of long term cultures-initiating cells (LTC-IC) assays and slightly differentiates colony forming cells (CFC). CD34+ Bone Marrow cells were isolated using MiniMACS system (Miltenyi, Paris, France).

RESULTS: A progressive decrease of CFC was noticed in placebo treated animals starting one month post-infection. One year after infection, all the animals (placebo and HAART treated) have decreased CFC of approximatively 56.5% of the pre-infection values. During primary infection, HAART treatement accelerates the decrease of CFC. One year after infection, a dramatic decrease (over 76.6%) of LTC-IC was notted in all the animals. No difference was observed between placebo or HAART treated monkeys. No correlation could be established with lymphopenia, circulating CD4+ cell numbers or plasma and cellular viremia.

CONCLUSION: The impact of the SHIV89.6P infection in macaque hematopoiesis is higher at the level of most primitives bone marrow CD34+ hematopoietics progenitors (LTC-IC) than more differenciated cells (CFC), with no evident relation to virological and immunological parameters of infection.

Keywords: AEGIS, Hematopoiesis, Macaca, Antigens, CD34, Bone Marrow, Antiretroviral Therapy, Highly Active, Bone Marrow Cells, SIV, Viremia, HIV-1, Cells, Cultured, CD4-Positive T-Lymphocytes, France, Paris, Animal, Human, immunology
000709
MoOrA173