Direct Induction of MHC Class I, but Not Class Ii, Expression on Endothelial Cells by Cytomegalovirus Infection

Wt, van Dorp; Jonges, E.; Bruggeman, C. A.; Mr, Daha; La, van Es; Fj, van der Woude

doi:10.1097/00007890-198909000-00024

Cited by 91 publications

(26 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The images clearly show that following CMV infection, the class I HLA heterodimer accumulates in the perinuclear area of the cytoplasm. uninfected cultures (van Dorp et al, 1989). However, in these studies only about 10 ~ of the endothelial cells were infected, and it could not be determined from the data presented whether the increased class I H L A expression was actually on the infected endothelial cells or on bystander uninfected cells in the same cultures.…”

Section: Discussionmentioning

confidence: 88%

Down-regulation of the class I HLA heterodimer and beta2-microglobulin on the surface of cells infected with cytomegalovirus

Barnes

Grundy

1992

Journal of General Virology

103

View full text Add to dashboard Cite

Cytotoxic T cell recognition of virus-infected cells requires the presentation of viral peptides by class I HLA molecules on the cell surface. We report here that cytomegalovirus (CMV) infection of human fibroblasts results in a progressive decrease in the cell surface expression of class I HLA and fl2-microglobulin (fl2m) such that in the late stages of infection the majority of infected cells have no detectable surface class I HLA. Coincident with decreased surface expression of class I HLA was an increase in his cytoplasmic expression. Confocal scanning laser microscopic analysis demonstrated that class I HLA and fl2m accumulate in a perinuclear compartment inside the CMV-infected cell. Our data thus support the concept that CMV infection induces altered transport of class I HLA to the cell surface. We suggest that the virus has evolved this mechanism as a strategy to avoid T cell recognition of infected cells.

show abstract

Section: Discussionmentioning

confidence: 88%

Down-regulation of the class I HLA heterodimer and beta2-microglobulin on the surface of cells infected with cytomegalovirus

Barnes

Grundy

1992

Journal of General Virology

103

View full text Add to dashboard Cite

show abstract

“…For example, CMV infection increases endothelial cell adhesive properties caused by increasing the levels of adhesion molecules and major histocompatibility complex class I and II molecules on their surface (19,48,52,54), which may increase immune-cell infiltration and activation. Furthermore, HCMV infection upregulates the expression of RANTES in SMC and fibroblasts (32,49), promoting cellular infiltration at sites of vascular injury.…”

Section: Posttransplantation) Grafts From Rcmv-infected Recipients Hmentioning

confidence: 99%

Cytomegalovirus-Mediated Upregulation of Chemokine Expression Correlates with the Acceleration of Chronic Rejection in Rat Heart Transplants

Streblow¹,

Kreklywich²,

Yin

et al. 2003

J Virol

108

View full text Add to dashboard Cite

Cytomegalovirus (CMV) infections have been shown to dramatically affect solid organ transplant graft survival in both human and animal models. Recently, it was demonstrated that rat CMV (RCMV) infection accelerates the development of transplant vascular sclerosis (TVS) in both rat heart and small bowel graft transplants. However, the mechanisms involved in this process are still unclear. In the present study, we determined the kinetics of RCMV-accelerated TVS in a rat heart transplant model. Acute RCMV infection enhances the development of TVS in rat heart allografts, and this process is initiated between 21 and 24 days posttransplantation. The virus is consistently detected in the heart grafts from day 7 until day 35 posttransplantation but is rarely found at the time of graft rejection (day 45 posttransplantation). Grafts from RCMV-infected recipients had upregulation of chemokine expression compared to uninfected controls, and the timing of this increased expression paralleled that of RCMV-accelerated neointimal formation. In addition, graft vessels from RCMV-infected grafts demonstrate the increased infiltration of T cells and macrophages during periods of highest chemokine expression. These results suggest that CMV-induced acceleration of TVS involves the increased graft vascular infiltration of inflammatory cells through enhanced chemokine expression.With the escalation in the number of immunosuppressed patients undergoing immunosuppressive therapy following solid organ or bone marrow transplantation, human cytomegalovirus (HCMV) disease has now become a major clinical problem. While the majority of HCMV infections result in subclinical disease in healthy individuals, HCMV is a significant pathogen in immunocompromised patients (1,3,4,9,26,33,34,50,51,56). Primary HCMV infection is followed by lifelong persistence of the virus in a latent state, and reactivation of the latent virus is considered to be the major source of virus in these immunocompromised individuals. HCMV has been linked to the development of atherosclerosis, arterial restenosis following angioplasty, and solid organ transplant vascular sclerosis (TVS) (26)(27)(28)47). HCMV infection doubles the 5-and 3-year rates of graft failure due to accelerated TVS in cardiac and liver transplant patients, respectively (15; L. W. Miller, Editorial, J. Heart Lung Transplant. 11:S1-S4, 1992). The observation that HCMV infects many of the cell types involved in vascular disease, including monocyte-derived macrophages, endothelial cells, and smooth muscle cells (SMC), suggests that HCMV may play a role in these disease processes. Because of the similarities between the CMV-speciesspecific viruses, animal models provide an ideal tool to study the association between CMV and TVS.The most compelling evidence that herpesviruses play a role in vascular disease comes from studies in animal models. Using a rat CMV (RCMV) solid organ transplant model, researchers have demonstrated, in light of the RCMV-associated acceleration of TVS, an association of herpesvirus ...

show abstract

“…For example, CMV infection of smooth muscle cells generates reactive oxygen species that activate NF-jB, a potent inducer of pro-inflammatory cytokines and chemokines (13). CMV-infected endothelial cells demonstrate enhanced expression of several cell surface molecules that are involved in the adhesion of leukocytes, such as ICAM-1, VCAM-1, VAP-1, E-selectin and MHC Class I antigens (9,14,15). Further more, in the presence of chemokines, such as RANTES and MCP-1, the infection induces migration of the inflammatory cells to the sites of chemokine production.…”

Section: In Vitro Studiesmentioning

confidence: 99%

“…Of all evaluated pathogens, only IgG seropositivity to HSV-2 (p = 0.05) and IgA seropositivity to EBV (p = 0.001) as well as H. pylori (p = 0.002) revealed an independent significant association with future cardiovascular death. However, when infectious burden was evaluated, patients seropositive to > 5 pathogens compared with those seropositive to <4 pathogens had a 5.1 (1,(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18) higher risk of future cardiac death. This result was mainly driven by the pathogen burden of seropositivities to Herpes viridae (p < 0.0001).…”

Section: Total Pathogen Burdenmentioning

confidence: 99%

The Role of Viruses in Cardiac Allograft Vasculopathy

Valantine

2004

American Journal of Transplantation

View full text Add to dashboard Cite

Considerable evidence suggests a role for viruses in transplant arteriosclerosis (TA), including observational data, experimental models and therapeutic trials implicating human cytomegalovirus (HCMV) in the progression to TA. In pediatric heart transplant patients, adenoviral genome in endomyocardial biopsies (EMB) is an important predictor of TA and graft loss. During CMV viremia, EMBs from adult patients demonstrate endothelialitis and vascular smooth muscle cell proliferation. These changes are predictors of subsequent diffuse TA. HCMV immediate early proteins (IE-1 and IE-2) increase the constitutive expression of intercellular adhesion molecule-1 (ICAM-1) independent of other intracellular cytokines. Likewise, viral chemokines such as US28 have been implicated in vascular disease because of their ability to induce smooth muscle cell migration. Recent data suggests that CMV might accelerate TA through its ability to abrogate the vascular protective effects of the endothelium-derived nitric oxide system (eNOS). Confirmation of causality requires clinical trials demonstrating that antiviral agents such as ganciclovir inhibit TA. Such studies in patients though limited to retrospective analyses, suggest that ganciclovir prophylaxis early after heart transplantation reduces the risk of TA. These observations emphasize the need for randomized controlled clinical trials to confirm a causal role for CMV (and other viruses) in TA.

show abstract

Direct Induction of MHC Class I, but Not Class Ii, Expression on Endothelial Cells by Cytomegalovirus Infection

Cited by 91 publications

References 0 publications

Down-regulation of the class I HLA heterodimer and beta2-microglobulin on the surface of cells infected with cytomegalovirus

Down-regulation of the class I HLA heterodimer and beta2-microglobulin on the surface of cells infected with cytomegalovirus

Cytomegalovirus-Mediated Upregulation of Chemokine Expression Correlates with the Acceleration of Chronic Rejection in Rat Heart Transplants

The Role of Viruses in Cardiac Allograft Vasculopathy

Contact Info

Product

Resources

About