#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Shedding Light on the Elusive Role of Endothelial Cells in Cytomegalovirus Dissemination


Cytomegalovirus (CMV) is frequently transmitted by solid organ transplantation and is associated with graft failure. By forming the boundary between circulation and organ parenchyma, endothelial cells (EC) are suited for bidirectional virus spread from and to the transplant. We applied Cre/loxP-mediated green-fluorescence-tagging of EC-derived murine CMV (MCMV) to quantify the role of infected EC in transplantation-associated CMV dissemination in the mouse model. Both EC- and non-EC-derived virus originating from infected Tie2-cre+ heart and kidney transplants were readily transmitted to MCMV-naïve recipients by primary viremia. In contrast, when a Tie2-cre+ transplant was infected by primary viremia in an infected recipient, the recombined EC-derived virus poorly spread to recipient tissues. Similarly, in reverse direction, EC-derived virus from infected Tie2-cre+ recipient tissues poorly spread to the transplant. These data contradict any privileged role of EC in CMV dissemination and challenge an indiscriminate applicability of the primary and secondary viremia concept of virus dissemination.


Vyšlo v časopise: Shedding Light on the Elusive Role of Endothelial Cells in Cytomegalovirus Dissemination. PLoS Pathog 7(11): e32767. doi:10.1371/journal.ppat.1002366
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1002366

Souhrn

Cytomegalovirus (CMV) is frequently transmitted by solid organ transplantation and is associated with graft failure. By forming the boundary between circulation and organ parenchyma, endothelial cells (EC) are suited for bidirectional virus spread from and to the transplant. We applied Cre/loxP-mediated green-fluorescence-tagging of EC-derived murine CMV (MCMV) to quantify the role of infected EC in transplantation-associated CMV dissemination in the mouse model. Both EC- and non-EC-derived virus originating from infected Tie2-cre+ heart and kidney transplants were readily transmitted to MCMV-naïve recipients by primary viremia. In contrast, when a Tie2-cre+ transplant was infected by primary viremia in an infected recipient, the recombined EC-derived virus poorly spread to recipient tissues. Similarly, in reverse direction, EC-derived virus from infected Tie2-cre+ recipient tissues poorly spread to the transplant. These data contradict any privileged role of EC in CMV dissemination and challenge an indiscriminate applicability of the primary and secondary viremia concept of virus dissemination.


Zdroje

1. FishmanJARubinRH 1998 Infection in organ-transplant recipients. N Engl J Med 338 1741 1751

2. Pouteil-NobleCEcochardRLandrivonGDonia-MagedATardyJC 1993 Cytomegalovirus infection—an etiological factor for rejection? A prospective study in 242 renal transplant patients. Transplantation 55 851 857

3. PlachterBSinzgerCJahnG 1996 Cell types involved in replication and distribution of human cytomegalovirus. Adv Virus Res 46 195 261

4. SinzgerCDigelMJahnG 2008 Cytomegalovirus cell tropism. Curr Top Microbiol Immunol 325 63 83

5. ManezRKusneSRinaldoCAguadoJMSt GeorgeK 1996 Time to detection of cytomegalovirus (CMV) DNA in blood leukocytes is a predictor for the development of CMV disease in CMV-seronegative recipients of allografts from CMV-seropositive donors following liver transplantation. J Infect Dis 173 1072 1076

6. CollinsTMQuirkMRJordanMC 1994 Biphasic viremia and viral gene expression in leukocytes during acute cytomegalovirus infection of mice. J Virol 68 6305 6311

7. GriffithBPChenMIsomHC 1990 Role of primary and secondary maternal viremia in transplacental guinea pig cytomegalovirus transfer. J Virol 64 1991 1997

8. EisenfeldLSilverHMcLaughlinJKlevjer-AndersonPMayoD 1992 Prevention of transfusion-associated cytomegalovirus infection in neonatal patients by the removal of white cells from blood. Transfusion 32 205 209

9. GilbertGLHayesKHudsonILJamesJ 1989 Prevention of transfusion-acquired cytomegalovirus infection in infants by blood filtration to remove leucocytes. Neonatal Cytomegalovirus Infection Study Group. Lancet 1 1228 1231

10. GrefteAHarmsenMCvan der GiessenMKnollemaSvan SonWJ 1994 Presence of human cytomegalovirus (HCMV) immediate early mRNA but not ppUL83 (lower matrix protein pp65) mRNA in polymorphonuclear and mononuclear leukocytes during active HCMV infection. J Gen Virol 75 Pt 8 1989 1998

11. IbanezCESchrierRGhazalPWileyCNelsonJA 1991 Human cytomegalovirus productively infects primary differentiated macrophages. J Virol 65 6581 6588

12. van der StrateBWHillebrandsJLLycklama a NijeholtSSBeljaarsLBruggemanCA 2003 Dissemination of rat cytomegalovirus through infected granulocytes and monocytes in vitro and in vivo. J Virol 77 11274 11278

13. AdlerBSinzgerC 2009 Endothelial cells in human cytomegalovirus infection: one host cell out of many or a crucial target for virus spread? Thromb Haemost 102 1057 1063

14. GrefteABlomNvan der GiessenMvan SonWTheTH 1993 Ultrastructural analysis of circulating cytomegalic cells in patients with active cytomegalovirus infection: evidence for virus production and endothelial origin. J Infect Dis 168 1110 1118

15. GrefteAvan der GiessenMvan SonWTheTH 1993 Circulating cytomegalovirus (CMV)-infected endothelial cells in patients with an active CMV infection. J Infect Dis 167 270 277

16. PercivalleERevelloMGVagoLMoriniFGernaG 1993 Circulating endothelial giant cells permissive for human cytomegalovirus (HCMV) are detected in disseminated HCMV infections with organ involvement. J Clin Invest 92 663 670

17. SinzgerCGrefteAPlachterBGouwASTheTH 1995 Fibroblasts, epithelial cells, endothelial cells and smooth muscle cells are major targets of human cytomegalovirus infection in lung and gastrointestinal tissues. J Gen Virol 76 Pt 4 741 750

18. KoffronAJHummelMPattersonBKYanSKaufmanDB 1998 Cellular localization of latent murine cytomegalovirus. J Virol 72 95 103

19. SeckertCKRenzahoATervoHMKrauseCDeegenP 2009 Liver sinusoidal endothelial cells are a site of murine cytomegalovirus latency and reactivation. J Virol 83 8869 8884

20. ZhouYFLeonMBWaclawiwMAPopmaJJYuZX 1996 Association between prior cytomegalovirus infection and the risk of restenosis after coronary atherectomy. N Engl J Med 335 624 630

21. KoskinenPKNieminenMSKrogerusLALemstromKBMattilaSP 1993 Cytomegalovirus infection and accelerated cardiac allograft vasculopathy in human cardiac allografts. J Heart Lung Transplant 12 724 729

22. SalzbergerBMyersonDBoeckhM 1997 Circulating cytomegalovirus (CMV)-infected endothelial cells in marrow transplant patients with CMV disease and CMV infection. J Infect Dis 176 778 781

23. SacherTJordanSMohrCAVidyAWeynAM 2008 Conditional gene expression systems to study herpesvirus biology in vivo. Med Microbiol Immunol 197 269 276

24. SacherTPodlechJMohrCAJordanSRuzsicsZ 2008 The major virus-producing cell type during murine cytomegalovirus infection, the hepatocyte, is not the source of virus dissemination in the host. Cell Host Microbe 3 263 272

25. ChouSWNormanDJ 1988 The influence of donor factors other than serologic status on transmission of cytomegalovirus to transplant recipients. Transplantation 46 89 93

26. RubinRHWilsonEJBarrettLVMedearisDN 1984 Primary cytomegalovirus infection following cardiac transplantation in a murine model. Transplantation 37 306 310

27. ShanleyJDBillingsleyAMShelbyJCorryRJ 1983 Transfer of murine cytomegalovirus infection by heart transplantation. Transplantation 36 584 586

28. HoMSuwansirikulSDowlingJNYoungbloodLAArmstrongJA 1975 The transplanted kidney as a source of cytomegalovirus infection. N Engl J Med 293 1109 1112

29. SagedalSNordalKPHartmannADegreMHolterE 2000 A prospective study of the natural course of cytomegalovirus infection and disease in renal allograft recipients. Transplantation 70 1166 1174

30. ToupanceOBouedjoro-CamusMCCarquinJNovellaJLLavaudS 2000 Cytomegalovirus-related disease and risk of acute rejection in renal transplant recipients: a cohort study with case-control analyses. Transpl Int 13 413 419

31. FennerF 1949 Mouse-pox; infectious ectromelia of mice; a review. J Immunol 63 341 373

32. SaederupNAguirreSASparerTEBouleyDMMocarskiES 2001 Murine cytomegalovirus CC chemokine homolog MCK-2 (m131-129) is a determinant of dissemination that increases inflammation at initial sites of infection. J Virol 75 9966 9976

33. GrundyJELawsonKMMacCormacLPFletcherJMYongKL 1998 Cytomegalovirus-infected endothelial cells recruit neutrophils by the secretion of C-X-C chemokines and transmit virus by direct neutrophil-endothelial cell contact and during neutrophil transendothelial migration. J Infect Dis 177 1465 1474

34. WaldmanWJKnightDAHuangEHSedmakDD 1995 Bidirectional transmission of infectious cytomegalovirus between monocytes and vascular endothelial cells: an in vitro model. J Infect Dis 171 263 272

35. StoddartCACardinRDBonameJMManningWCAbenesGB 1994 Peripheral blood mononuclear phagocytes mediate dissemination of murine cytomegalovirus. J Virol 68 6243 6253

36. HsuKMPrattJRAkersWJAchilefuSIYokoyamaWM 2009 Murine cytomegalovirus displays selective infection of cells within hours after systemic administration. J Gen Virol 90 33 43

37. BöhmVSimonCOPodlechJSeckertCKGendigD 2008 The immune evasion paradox: immunoevasins of murine cytomegalovirus enhance priming of CD8 T cells by preventing negative feedback regulation. J Virol 82 11637 11650

38. Cicin-SainLPodlechJMesserleMReddehaseMJKoszinowskiUH 2005 Frequent coinfection of cells explains functional in vivo complementation between cytomegalovirus variants in the multiply infected host. J Virol 79 9492 9502

39. ConstienRFordeALiliensiekBGroneHJNawrothP 2001 Characterization of a novel EGFP reporter mouse to monitor Cre recombination as demonstrated by a Tie2 Cre mouse line. Genesis 30 36 44

40. WagnerMJonjicSKoszinowskiUHMesserleM 1999 Systematic excision of vector sequences from the BAC-cloned herpesvirus genome during virus reconstitution. J Virol 73 7056 7060

41. MenardCWagnerMRuzsicsZHolakKBruneW 2003 Role of murine cytomegalovirus US22 gene family members in replication in macrophages. J Virol 77 5557 5570

42. CorryRJWinnHJRussellPS 1973 Primarily vascularized allografts of hearts in mice. The role of H-2D, H-2K, and non-H-2 antigens in rejection. Transplantation 16 343 350

43. RussellPSChaseCMColvinRBPlateJM 1978 Kidney transplants in mice. An analysis of the immune status of mice bearing long-term, H-2 incompatible transplants. J Exp Med 147 1449 1468

Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

Článok vyšiel v časopise

PLOS Pathogens


2011 Číslo 11
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Získaná hemofilie - Povědomí o nemoci a její diagnostika
nový kurz

Eozinofilní granulomatóza s polyangiitidou
Autori: doc. MUDr. Martina Doubková, Ph.D.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#