In vitro and in vivo susceptibility of mouse megakaryocytic progenitors tostrain i of parvovirus minute virus of mice

Objective. Intranasal inoculation of the i strain of the parvovirus minute virus of mice (MVMi) into immunodeficient SCID mice induces suppression of myeloid and erythroid progenitors in the bone marrow (BM) and lethal leukop enia. In the present study, we investigated whether the mouse megakaryocyti c lineage was susceptible to MVMi. Materials and Methods. In vitro and in vivo infections with purified MVMi w ere conducted and their effects on the megakaryocytic lineage studied. Results. In vitro infection of BM cells showed a multiplicity of infection- dependent inhibition in the colony-forming ability of megakaryocytic progen itors (colony-forming unit megakaryocyte [CFU-MK]). Neutralization or heat inactivation of the virus abrogated this inhibition. Expression of the MVMi nonstructural-1 protein was detected in the in vitro infected and cultured megakaryocytic cells. In vivo, intranasal inoculation of a lethal dose of virus was incapable of producing significant thrombocytopenia, although an increase in mean platelet volume was observed. Significantly, in the BM of these animals, a progressive decrease in CFU-MK was noted from day 14 posti nfection, with survival rates less than 1% by day 35 postinfection. At day 35 postinfection, intermediate megakaryocytic differentiation stages showed maintenance of the proportion and ploidy of cells and a moderate decrease in the total number of these cells per femoral BM. Conclusions. The results demonstrate that MVMi is capable of inhibiting the proliferative capacity of megakaryocytic committed progenitors both in vit ro and in vivo. Moreover, the in vivo data show that depletion of BM CFU-MK is compensated by the system, and platelet counts in the peripheral blood are maintained close to normal values. (C) 2001 International Society for E xperimental Hematology. Published by Elsevier Science Inc.