Evaluation of Murine Leukemia Virus Infection as a Model for Thrombocytopenia of HIV/AIDS: Mechanism of Thrombocytopenia and Modulation of Thrombocytopenia by Thrombopoietin

Abstract

Infection of mice with the murine leukemia virus (LP-BM5) was evaluated as a model for the thrombocytopenia of HIV/AIDS. Percent 35S incorporation into platelets, platelet size, platelet count, platelet-associated immunoglobulins (PAIgG), and megakaryocyte size and number were evaluated over a period of 3-9 weeks postinfection (PI). Thrombopoietin from human embryonic kidney cells was administered to mice 9 weeks PI, and similar indices of platelet production were measured 2, 3, and 4 days after treatment with a biological preparation of thrombopoietin (thrombocytopoiesis-stimulating factor, or TSF). Platelet counts decreased in a time-dependent fashion (p = 0.0006) following infection, reaching a nadir at 8 weeks PI (82% of control values). Percent 35S incorporation into platelets also decreased over the 9-week period (p = 0.0001), falling to 63% of control values by week 9. Additionally, platelet volume increased in a linear fashion (p = 0.01), rising to 105% of control values by week 9. No changes in PAIgG were noted over the 9-week period. Megakaryocyte numbers in the femoral marrow were decreased at 8 weeks PI (p = 0.02, 78% of control values), while increased mean megakaryocyte size (p = 0.007, 116% of controls) was noted in the same animals. Increased numbers of naked megakaryocyte nuclei were observed at 3 weeks PI (p < 0.05, 208% of control values). Administration of 2 U/mouse of a highly purified preparation of TSF to virus-infected, thrombocytopenic mice resulted in increased thrombocytopoiesis, as compared to human serum albumin-treated, virus-infected controls.(ABSTRACT TRUNCATED AT 250 WORDS)