Strain Specific Effects of Cytomegalovirus on Endothelial Cells: Implications for Investigating the Relationship Between CMV and Cardiac Allograft Vasculopathy1

Srivastava, Rohit; Curtis, Michelle; Hendrickson, Sara M; Burns, William H.; Hosenpud, Jeffrey D.

doi:10.1097/00007890-199911270-00022

Cited by 27 publications

(14 citation statements)

References 20 publications

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“…HCMV decreases the expression of MHC class I molecules on fibroblasts 12 and on endothelial cells 25 and partially downregulates surface expression of MHC class I molecules on human macrophages 26 by multiple mechanisms. The finding of down-regulation of MHC class I molecules on DCs is in agreement with these studies.…”

Section: Discussionmentioning

confidence: 99%

Human cytomegalovirus inhibits maturation and impairs function of monocyte-derived dendritic cells

Moutaftsi

Mehl

Borysiewicz

et al. 2002

Blood

205

208

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Whereas virus infections in general stimulate DC maturation and lead to the generation of efficient antiviral T-cell responses, some viruses have developed mechanisms to interfere with the normal functions of DCs. Human immunodeficiency virus (HIV), measles virus, herpes simplex virus-1 (HSV-1), and vaccinia virus, for example, are all known to cause defects in DC maturation and function which consequently lead to impaired antiviral T-cell responses. [1][2][3][4] The major risk factor for HCMV infection in bone marrow transplant patients is their pre-existing seropositive status. 5 Delayed reconstitution of the antiviral cellular immune response in these patients is often associated with HCMV infection and progressive disease with poor prognosis. CD8 ϩ T cells are the main cell type controlling HCMV infection as proven by their successful adoptive transfer preventing viraemia and HCMV disease in bone marrow transplant recipients. 6 HCMV infection is also associated with serious secondary bacterial or fungal infections in immunosuppressed patients, 7,8 although during the early phase of acute HCMV infection, transiently suppressed cellular immune responses 9,10 and immunologic abnormalities of healthy individuals 11 were also reported. HCMV has been shown to interfere with antigen presentation in fibroblasts and endothelial cells 12 by (1) expressing viral proteins which interfere with the MHC class I antigenpresenting pathways (US3, US2, US11); (2) modulating antigen procession of the HCMV immediate early 1 (IE1) protein (pp65); and (3) preventing peptide transport through TAP proteins (US6). However, little is known about whether the induction phase of HCMV-specific T-cell responses is also affected. From the few studies that looked at HCMV infection of monocytes, macrophages, and DCs, [13][14][15] only one seemed to establish a link between HCMV infection of macrophages and impaired proliferation of CD4 ϩ T cells upon stimulation with these macrophages. 15 We hypothesized that similar to its effects in fibroblasts and endothelial cells, HCMV also inhibits the expression of MHC class I molecules in DCs. Although this inhibitory effect alone would probably be sufficient to prevent or impair the generation of virus-specific primary T-cell responses, other important features such as the expression of costimulatory molecules, the production of proinflammatory cytokines, and the antigen-presenting function of monocyte-derived DCs were also studied following HCMV infection. We show that HCMV impairs all these properties of DCs. The viral inhibition may contribute not only to the successful establishment of latency by HCMV but also to the immunosuppression observed in association with the infection. Patients, materials, and methods DonorsHCMV seropositive and seronegative healthy laboratory volunteers were included in this study. Ethical approval was obtained and informed consent Cell lines and tissue culture reagentsHuman foreskin fibroblasts (HFFs) were cultured in minimum essential medium (MEM; Sigma, St Louis, MO...

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Section: Discussionmentioning

confidence: 99%

Human cytomegalovirus inhibits maturation and impairs function of monocyte-derived dendritic cells

Moutaftsi

Mehl

Borysiewicz

et al. 2002

Blood

205

208

View full text Add to dashboard Cite

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“…Another mechanism of cellular accumulation occurs through SMC proliferation at the site of vascular injury. CMV infection of endothelial cells induces the release of growth factors and cytokines, including fibroblast growth factor and platelet-derived growth factor BB, which are potent stimuli of SMC proliferation (30). Furthermore, HCMV infection up-regulates expression of the CC chemokine RANTES in SMCs and fibroblasts (23,32).…”

Section: Discussionmentioning

confidence: 99%

Mouse Cytomegalovirus M33 Is Necessary and Sufficient in Virus-Induced Vascular Smooth Muscle Cell Migration

Melnychuk¹,

Smith²,

Kreklywich

et al. 2005

J Virol

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Mouse cytomegalovirus (MCMV) encodes two potential seven-transmembrane-spanning proteins with homologies to cellular chemokine receptors, M33 and M78. While these virus-encoded chemokine receptors are necessary for the in vivo pathogenesis of MCMV, the function of these proteins is unknown. Since vascular smooth muscle cell (SMC) migration is of critical importance for the development of atherosclerosis and other vascular diseases, the ability of M33 to promote SMC motility was assessed. Similar to human CMV, MCMV induced the migration of mouse aortic SMCs but not mouse fibroblasts. To demonstrate whether M33 was required for MCMV-induced SMC migration, we employed interfering-RNA technology to specifically knock down M33 expression in the context of viral infection. The knockdown of M33 resulted in the specific reduction of M33 protein expression and ablation of MCMV-mediated SMC migration but failed to reduce viral growth in cultured cells. Adenovirus vector expression of M33 was sufficient to promote SMC migration, which was enhanced in the presence of recombinant mouse RANTES (mRANTES). In addition, M33 promoted the activation of Rac1 and extracellular signal-related kinase 1/2 upon stimulation with mRANTES. These findings demonstrate that mRANTES is a ligand for this chemokine receptor and that the activation of M33 occurs in a ligand-dependent manner. Thus, M33 is a functional homologue of US28 that is required for MCMV-induced vascular SMC migration.

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“…[25][26][27][28] Toyoda et al 29 reported that elevated AECA levels were seen in 80% of transplant recipients with evidence of CMV infection, suggesting that CMV infection may trigger AECA synthesis. In the present study, nine recipients had CMV infections, and in these patients, the serum levels of AECA against HUVEC and MvE were enhanced a few weeks after CMV infection.…”

Section: Discussionmentioning

confidence: 99%

Serum antibody activity to glomerular endothelial cells is a prospective indicator of renal allograft rejection

Nakagawa

Saito

Morioka

et al. 2002

Clinical and Experimental Nephrology

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Background. Vascular endothelial ells (ECs) are considered to be a primary target for injury in allograft rejection. However, the relationship between serum antibody activity to ECs and rejection episodes has not been extensively examined in renal transplantation. Methods. Twenty-two renal transplant recipients were included in this study. Serum levels of anti-endothelial cell antibody (AECA) were measured using a cellular enzymelinked immunosorbent assay (ELISA) in which human umbilical vein endothelial cells (HUVEC), human glomerular endothelial cells (HGEC), and human dermal microvascular endothelial cells (MvE) were used as target cells. Serum samples were obtained just before transplantation and once a week during the immediate 1-to 3-month posttransplantation period. Results. There was a significant correlation between the the presence of AECA against HGEC and rejection episodes (P Ͻ 0.05). Patients with multiple episodes of rejection showed significantly higher frequencies of AECA than patients with a single episode of rejection (P Ͻ 0.001). It should be noted that patients suffering from multiple episodes of rejection had higher AECA titers than those without a rejection episode before transplantation. Conclusions. These findings imply that the HGEC-ELISA could be used as a prospective, informative test to identify patients at a high risk of acute rejection in renal transplantation.

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Strain Specific Effects of Cytomegalovirus on Endothelial Cells: Implications for Investigating the Relationship Between CMV and Cardiac Allograft Vasculopathy1

Cited by 27 publications

References 20 publications

Human cytomegalovirus inhibits maturation and impairs function of monocyte-derived dendritic cells

Human cytomegalovirus inhibits maturation and impairs function of monocyte-derived dendritic cells

Mouse Cytomegalovirus M33 Is Necessary and Sufficient in Virus-Induced Vascular Smooth Muscle Cell Migration

Serum antibody activity to glomerular endothelial cells is a prospective indicator of renal allograft rejection

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