?(Fig.7C).7C). accumulation of computer virus DNA replicative intermediates and the yield of infectious computer virus. Viral productive contamination was limited to a small subset of primitive cells expressing 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 twofold absolute increase in erythroid cells (TER-119+). Rabbit Polyclonal to SLC9A3R2 A stimulated definitive erythropoiesis in the infected mice was further evidenced by a 12-fold increase per femur of recognizable proerythroblasts, a quantitative apoptosis confined to uninfected TER-119+ cells, as well as by a 4-fold elevation in the number of circulating reticulocytes. Therefore, MVMi targets and suppresses primitive hemopoietic progenitors leading to a very severe leukopenia, but compensatory mechanisms are mounted specifically by the erythroid lineage Kaempferol that maintain an effective erythropoiesis. The results show that contamination of SCID mice with the parvovirus MVMi causes a novel dysregulation of murine hemopoiesis in vivo. The hemopoietic system displays a wide repertoire of proliferating cells at diverse differentiation and commitment stages generated from a small group of pluripotent stem cells (50). The tight control of this development is usually exerted by a network of signaling pathways onset by cellular interactions and growth factors binding to their cognate receptors (reviewed in recommendations 21, 39, and 55). Many viral infections are accompanied by the perturbation of hemopoiesis homeostasis (72, 70). The complexity of mechanisms underlying these alterations extends from the direct action of virus-coded effectors to the concourse of host regulatory factors. The infection of viruses belonging to the family is commonly associated with hematological diseases. This family includes a large group of small viruses made up of a linear single-stranded (ss) DNA genome with a nonenveloped 25-nm-diameter icosahedral capsid (57). The genome encodes nonstructural (NS1 and NS2) and structural proteins (VP1 and VP2) that form parvovirus particles. The major nonstructural protein NS1 is essential for replication and packaging of the viral genome (4, 17, 52) and transcriptional activity (22, 23) and is toxic to the host cell (15, 37, 42); therefore, its expression is usually a major indication of permissive parvoviral contamination. A general feature of parvoviruses multiplication is the requirement for functions expressed during the S phase of the cell cycle (5, 61, 63). This explains why a common characteristic in the pathogenesis of these viruses is the contamination of mitotically active cells and why clinical courses are more severe in developing hosts with many tissues undergoing proliferation (56, 59). Parvovirus tropism is also constrained by factors expressed at certain differentiation stages (40, 58, 62). In fact, the target cell specificity differs among the parvoviruses, and therefore their infections are accompanied by characteristic alterations of the lymphohemopoietic system. Aleutian mink disease parvovirus (ADV) causes a persistent contamination with severe disorders of the immune system of this animal (43, 48). Experimental and natural infections with the feline panleukopenia computer virus develops neutropenia in cats (34C36). The parvovirus B19 is the only known member of the Kaempferol that is pathogenic to humans (65, 71). The computer Kaempferol virus shows a selective tropism for hemopoietic precursors of the erythroid lineage (28, 44), interacting for the infection with the glycolipid globoside of the blood group P antigens that acts as a receptor of the computer virus (13, 16). The B19 is the etiological agent of a childhood measles-like rash called erythema infectiosum or fifth disease (1), and its intranasal inoculation into volunteers caused transient changes in the reticulocyte and hemoglobin (2) counts and a reduction in peripheral and marrow erythroid.