Study On The Latent Infection Of Mononuclear Cells With MCMV In The Bone Marrow Of Mouse

Human cytomegalovirus(HCMV)is a ubiquitous opportunisticβ-herpes virus,the infection rate of which ranges between 50 % to 80 % in the healthy population. Generally,there is no or unclear clinical symptoms,however, HCMV can reside in the peripheral blood and bone marrow in the form of latency in the host, with whom accompanying all the life,and can disseminate through blood products or solid organ transplantation.Reactivation of HCMV from latency can result in severe diseases when someone is immunodepressed. In the suffers exposed to bone marrow transplantation,the death rate resulted from the infection of HCMV is secend higher than that resulted from Graft-Versus-Host disease.As to the severe harm of latent infection of HCMV to the population inmmunocompromised, many researchers have udertook deeply studies on latent infection of HCMV.Infection of mouse with MCMV is an important animal model, mainly because the genome of MCMV is linear correlation with that of HCMV,and the 200 open reading frames have 45.2 % similarity to HCMV, 78 proteins coded by the two CMVs are homologous.Both HCMV and MCMV can cause serious infection in the their specific hosts accompanying with similar clinical symptoms,especially the effect on the hematopoietic system.Many researches have found that,after infection of mouse with MCMV,many changes happened in the murine hematopietic cells,including reduction of the number of peripheral blood leucocytes,blood platelets,monocyte-macrophage colony-forming units and their precursors,burst erythrocyte colony-forming units,which are very similar to the infection of human hematopietic cells with HCMV.Study of the effect on the infect- ion of human hemotopietic cells with murine model and analysis of the pathogenesis of primary infection,latent infection and reactivation will be of great significance to further study the pathog- enesis of the latent infection and reactivation of HCMV. Researches have proved that HCMV can be latent in human marrow,but there is no a confirmed conclusion about what kind of cells does the virus reside in.To confirm the exact position of HCMV in the marrow,we use a murine model to carry out our research on the infection of murine hametop~- oietic system with MCMV,especially the latent infection of marrow mononuclear cells and their subpopulations.1 Study on the latent infection of marrow mononuclear cells with MCMV.In vitro results reveal that ,after infecion of mononuclear cells, MCMV DNA,mRNA and protein of immediate early gene can be detected except for early genes;the infection can inhibit the formation of mononuclear cells.These results hint that MCMV can infect mononuclear cells in vitro.In vivo results reveal that after inoculation of MCMV directly through belly cavity to the mouse, MCMV DNA can be detected in the peripheral blood and marrow cells during different times post-infection,and the number of marrow mononuclear cells ranges from decline to lift when time prolongs.All the in vivo studies suggest that infection in the mouse can inhibit the hemotopoiesis of marrow in short time .2 Latent infection of different subpopulations of marrow mononuclear cells. MCMV attack the four kinds of cells after mononuclear cells being separated into four subpopulations,including lin~+ cells,lin~- cells,lin~-cd117~+ cells,lin~-cd117~- cells.Results reveal that MCMV DNA,IE transcrip (but no E transcrip)and protein can be deteced in the lin~+ cells;however,no IE and E transcrips are detected in the lin~- cells,lin~-cd117~+ cells and lin~-cd117~- cells,and no protein is found with indirect immunofluorescence.But,the number of colony forming units derived from lin~-cd117~+ cells infected apparently lower than normal lin~-cd117~+ cells,that is to say infection with MCMV can inhibit the function of colony forming units of murine marrow hamotopoietic stem and progenitor ells;and ,the expression of the CD117 antigen which is be a maker of stem and progenitor cells is more downre~- gulated than normal cells did.When adding the cytokines(such as GM-CSFor rhEPO),or indcer(for example of phorbol ester),to the lin~- cells infected with MCMV, IE and E proteins can be detected,th~- at is to say cytokines and inducers maybe contribute to the infection of MCMV in the course of inducing cell to differentiation.The study results have proved that MCMV can latently infect murine marrow mononuclear cells and their lin~+ subpopulation,and can produce some transcripts and proteins in some extra conditions.lin~- subpopulation cells including hamotopoietic stem and progenitor cells are possiblely not susceptible to the MCMV,but , adding the cytokines or inducer to the cells can promote the infection.Besides,attack of lin~-cd117~+ cells with MCMV can affect the function and phenotype of these cells. All the above results lay the foundation for further study on the latency and reactivation of MCMV in the marrow,but the pathogenic mechanism should be studied deeply.