Severe leukopenia and dysregulated erythropoiesis in SCID mice persistently infected with the parvovirus minute virus of mice

Parvovirus minute virus of mice strain i (MVMi) infects committed granulocy te-macrophage CFU and erythroid burst-forming unit (CFU-GM and BFU-E, respe ctively) and pluripotent (CFU-S) mouse hematopoietic progenitors in vitro. To study the effects of MVMi infection on mouse hemopoiesis in the absence of a specific immune response, adult SCID mice were inoculated by the natur al intranasal route of infection and monitored for hematopoietic and viral multiplication parameters. Infected animals developed a very severe viral-d ose-dependent leukopenia by 30 days postinfection (d.p.i.) that led to deat h within 100 days, even though the number of circulating platelets and eryt hrocytes remained unaltered throughout the disease. In the bone marrow of e very lethally inoculated mouse, a deep suppression of CFU-GM and BFU-E clon ogenic progenitors occurring during the 20- to 35-d.p.i. interval correspon ded with the maximal MVMi production, as determined by the accumulation of virus DNA replicative intermediates and the yield of infectious virus. Vira l productive infection was limited to a small subset of primitive cells exp ressing the major replicative viral antigen (NS-1 protein), the numbers of which declined with the disease. However, the infection induced a sharp and lasting unbalance of the marrow hemopoiesis, denoted by a marked depletion of granulomacrophagic cells (GR-1(+) and MAC-1(+)) concomitant with a twof old absolute increase in erythroid cells (TER-119(+)). A stimulated definit ive erythropoiesis in the infected mice was further evidenced by a 12-fold increase per femur of recognizable proerythroblasts, a quantitative apoptos is confined to uninfected TER-119(+) cells, as well as by a 4-fold elevatio n in the number of circulating reticulocytes. Therefore, MVMi targets and s uppresses primitive hemopoietic progenitors leading to a very severe leukop enia, but compensatory mechanisms are mounted specifically by the erythroid lineage that maintain an effective erythropoiesis. The results show that i nfection of SCID mice with the parvovirus MVMi causes a novel dysregulation of murine hemopoiesis in vivo.