1 / 15

Antje Ksienzyk Department of Gene Regulation and Differentiation aks08@helmholtz-hzi.de

Antje Ksienzyk Department of Gene Regulation and Differentiation aks08@helmholtz-hzi.de. model of systemic virus infection. Infection. Replication in first organ Primary viremia. Secondary viremia. other organs. dissemination. Replication. MCMV. Herpesviridae  herpesvirus

chana
Download Presentation

Antje Ksienzyk Department of Gene Regulation and Differentiation aks08@helmholtz-hzi.de

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Antje Ksienzyk Department of Gene Regulation and Differentiation aks08@helmholtz-hzi.de

  2. model of systemic virus infection Infection Replication in first organ Primary viremia Secondary viremia other organs dissemination Replication

  3. MCMV • Herpesviridae •  herpesvirus • Cytomegalovirus • MCMV: mouse cytomegalovirus HCMV :major risk factor for immunoincompetent and immunocompromised patients (AIDS patients and organ transplant recipients) MCMV: represents the rodent model MCMV replicates in a broad spectrum of cell types: vascular endothelial cells and hepatocytes

  4. The Cre-Loxp system

  5. The used Cre-Loxp system

  6. MCMV- flox and –rec replicate in the same manner

  7. Experimental set-up

  8. EC and HC are important cell types for MCMV replication 106 PFU of MCMV flox Analyses of MCMV-rec and MCMV-flox plaque forming units Tie2-cre: Cre under control of Tie2 (endothelial tyrosinkinase receptors: only in EC) promoter in vascular EC Alb-cre: Cre under control of albumin promoter in hepatocytes

  9. Hepatocytes are the main producer cell type Hepatocytes derived MCMV-rec do not disseminate from the liver to other organs (alb-cre)

  10. Influence of route and dose Alb-cre Amount of cre expression, the route and dose of infection have no influence on the results

  11. Hc-derived MCMV has potential to replicate in spleen and lung Virus isolation out of liver Alb-cre i.v. injection C57BL/6

  12. Bidirectional spread of MCMV between EC and Hc Tie2-cre: MCMV from EC to Hc Alb-cre: MCMV from Hc to EC EC and Hc produce virus which can infect neighboring cells No explanation that Hc derived virus can’t disseminate

  13. MCMV infection is controlled by CD3+ cells Elimination of MCMV is correlated with liver infiltrating T-cells Reason for dissemination stop?

  14. Immunosuppression has no influence on Hc- derived virus dissemination • untreated • + immunodepleted 1 untreated 2, 3 -irradiation 4 immune suppression by cyclophosphamide 5 proinflammatory stimuli. Con A No increase of dissemination after immune suppression and proinflammatory stimuli

  15. summary • Hepatocytes and EC are target cells of MCMV in vivo (replication) • HC are important target cells but are not involved in virus dissemination • Infected EC contribute to viremic dissemination by serving as transport vehicle and by uptake and release of virus • Hc derived MCMV never leads to a second viremia (unlike to former publications) • But what is the reason for that? • Independent on immune cells or irradiation • Independent on ability to infect other cells • IFN???

More Related