MARROW ACCESSORY CELL INFECTION AND ALTERATIONS IN HEMATOPOIESIS ACCOMPANY SEVERE NEUTROPENIA DURING EXPERIMENTAL ACUTE INFECTION WITH FELINE IMMUNODEFICIENCY VIRUS

Severe neutropenia and bone marrow (BM) morphologic abnormalities occu r during experimentally induced primary infection with feline immunode ficiency virus (FIV), a lentivirus biologically similar to human immun odeficiency virus (HIV). To further characterize the mechanisms involv ed in this acute infection model of lentivirus-induced BM suppression, peripheral blood counts, histologic BM studies, and BM culture assays were performed on 12 cats that underwent necropsy at regular interval s postinoculation (PI) with FIV Petaluma. Plasma viremia developed at week 3 PI and neutropenia was initially detected at week 6 PI. Low neu trophil counts, but normal hematocrits and platelet counts, persisted through week 12 PI. Infected BM mononuclear cells and megakaryocytes w ere identified by in situ hybridization assays for FIV nucleic acids i n BM sections of cats that underwent necropsy at weeks 4 to 12 PI, cor relating with detection of soluble FIV p24 antigen and identification of infected mononuclear and macrophage cells in BM buffy-coat cell cul tures from these cats. At weeks 1.5 to 4 PI, the mean frequencies (num ber per 10(5) BM mononuclear cells) of erythroid progenitors (erythroi d colony-forming units [CFU-E] and erythroid burst-forming units [BFU- E]) and granulocyte/macrophage progenitors (CFU-granulocyte/macrophage [CFU-GM]) were increased to 508 +/- 74, 143 +/- 24, and 110 +/- 17, r espectively (n = 5 cats) as compared with controls (172 +/- 24, 86 +/- 26, and 44 +/- 10; n = 3 cats; P < .02), and the percentages of proge nitors in the DNA-synthetic phase of the cell cycle were equivalent to controls. In contrast, the progenitor frequencies at weeks 6 to 12 PI were significantly decreased (72 +/- 16, 43 +/- 6, and 19 +/- 4, resp ectively; n = 7 cats; P < .01), and these progenitors were more freque ntly in S-phase. Autologous serum significantly inhibited (P < .05) th e growth of CFU-GM in 6 of 9 cats and failed to support the maximal gr owth of BFU-E in 4 of 9 cats studied at weeks 4 to 12 PI, whereas no s uch abnormalities were observed in colony assays containing autologous sera from control cats (n = 3) or cats studied at weeks 1.5 or 3 PI ( n = 3). In comparison, sera from FIV-infected cats did not inhibit the growth of normal, allogeneic progenitors. However, FIV serum frequent ly failed to support maximal in vitro growth of normal CFU-GM as compa red with uninfected allogeneic sera, further suggesting a lack of prog enitor growth-promoting substances in infected cat sera. Together, the se studies show that neutropenia induced by experimental acute FIV inf ection is associated with plasma viremia, with the appearance of viral -infected BM accessory cells, and with alterations in progenitor frequ encies, cell cycle kinetics, and in vitro growth in autologous sera. B ecause these virologic, hematologic, and hematopoietic abnormalities r esemble those associated with late-stage HIV infection, acute FIV infe ction may provide an excellent model to characterize the lentiviral an d host cell factors relevant to mechanisms of BM suppression in the ac quired immunodeficiency syndrome. (C) 1995 by The American Society of Hematology.