AEGiS-14IAC: Impact of bone marrow hematopoiesis failure in T-cell production during SIV/SHIV infection of macaques.

14th International AIDS Conference

Barcelona, Spain - July 7-12, 2002

Impact of bone marrow hematopoiesis failure in T-cell production during SIV/SHIV infection of macaques.

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. WeOrA1349)

Thiebot H, Vaslin B, de Revel T, Derdouch S, Gras G, Bertho JM, Louache F, Vainchenker W, Dormont D, Grand RL
Service de Neurovirologie, France, France

BACKGROUND: To evaluate, in macaque models of AIDS, the impact of infection on bone marrow hematopoiesis.

METHODS: Cynomolgus macaques have been inoculated with 50 MID50 of a SIVmac251 primary isolate or the SHIV89.P chimera which expresses the env gene of the primary HIV-1 89.6 isolate in a SIVmac239 background. During primary infection, animals infected with SHIV 89.6P were treated twice a day with either placebo or with the association of AZT, 3TC and Indinavir (HAART). Virological and immunological parameters were followed during one year. Purified CD34+ bone marrow cells (over 99% pure) were used for the detection of long term culture-initiating cells (LTC-IC), colony forming cells (CFC) or generation of T cells in coculture with thymic stromal cells. A gag PCR was used for the detection the virus DNA in bone marrow cells.

RESULTS: All the macaques exhibited decreased CFC, starting as early as primary infection regardless the virus strain used. One year pi., CFC was reduced of approximately 56% of pre-infection values and a dramatic reduction (over 77%) of primitive long-term culture initiating cells (LTC-IC) was noticed. Virus DNA could not be evidenced in purified bone marrow cells. Hematopoietic failure could not be prevented by early HAART, although antiviral treatment during primary infection results in a significant reduction of viral load and prevention from dramatic circulating CD4+ T cell loss. Generation of T cells in thymic stromal layers was significantly reduced in all SIV or SHIV infected macaques as early as primary infection. No correlation could be established between impaired progenitor growth and CD4+ lymphopenia or plasma viremia.

CONCLUSIONS: lentiviral infection have a strong impact on myelopoiesis and de novo generation of T-cells, independently of direct virus infection of hematopoietic cells.

Keywords: AEGIS, SIV, Macaca, Simian Acquired Immunodeficiency Syndrome, Hematopoiesis, T-Lymphocytes, Antiretroviral Therapy, Highly Active, HIV-1, Pancytopenia, CD4-Positive T-Lymphocytes, Viral Load, Genes, env, Bone Marrow, Viremia, Acquired Immunodeficiency Syndrome, Bone Marrow Cells, Animal, genetics

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