Marrow accessory cell infection and alterations in hematopoiesis accompany
severe neutropenia during experimental acute infection with feline
immunodeficiency virus
ML Linenberger, AM Beebe, NC Pedersen, JL Abkowitz and S Dandekar
Department of Medicine, University of Washington Seattle 98195.
Severe neutropenia and bone marrow (BM) morphologic abnormalities occur
during experimentally induced primary infection with feline
immunodeficiency virus (FIV), a lentivirus biologically similar to human
immunodeficiency virus (HIV). To further characterize the mechanisms
involved 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
intervals postinoculation (PI) with FIV Petaluma. Plasma viremia developed
at week 3 PI and neutropenia was initially detected at week 6 PI. Low
neutrophil counts, but normal hematocrits and platelet counts, persisted
through week 12 PI. Infected BM mononuclear cells and megakaryocytes were
identified by in situ hybridization assays for FIV nucleic acids in BM
sections of cats that underwent necropsy at weeks 4 to 12 PI, correlating
with detection of soluble FIV p24 antigen and identification of infected
mononuclear and macrophage cells in BM buffy-coat cell cultures from these
cats. At weeks 1.5 to 4 PI, the mean frequencies (number per 10(5) BM
mononuclear cells) of erythroid progenitors (erythroid 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, respectively (n =
5 cats) as compared with controls (172 +/- 24, 86 +/- 26, and 44 +/- 10; n
= 3 cats; P < .02), and the percentages of progenitors 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, respectively; n = 7 cats; P
< .01), and these progenitors were more frequently in S-phase.
Autologous serum significantly inhibited (P < .05) the growth of CFU-GM
in 6 of 9 cats and failed to support the maximal growth of BFU-E in 4 of 9
cats studied at weeks 4 to 12 PI, whereas no such 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 frequently failed to support maximal in
vitro growth of normal CFU-GM as compared with uninfected allogeneic sera,
further suggesting a lack of progenitor growth- promoting substances in
infected cat sera.(ABSTRACT TRUNCATED AT 400 WORDS)
Volume 85,
Issue 4,
pp. 941-951,
02/15/1995
Copyright © 1995 by The American Society of Hematology
