The Human Cytomegalovirus Chemokine Receptor US28 Mediates Vascular Smooth Muscle Cell Migration

Streblow, Daniel N.; Söderberg‐Nauclér, Cecilia; Vieira, Jeffrey; Smith, Patricia; Wakabayashi, Eiko; Ruchti, Franziska; Mattison, Kirsten; Altschuler, Yoram; Nelson, Jay A.

doi:10.1016/s0092-8674(00)81539-1

Cited by 392 publications

(361 citation statements)

References 54 publications

Supporting

Mentioning

336

Contrasting

Unclassified

Order By: Relevance

“…Attraction and activation of leukocyte populations by virus-encoded chemokines and chemokine receptors may play central roles in orchestrating the progression of diseases that have an inflammatory basis, such as CAV. This possibility has been highlighted in recent publications and reviews (51,52) that stress the connection of this virus to native atherosclerosis. One of the chemokine homologs, pUL146 (vCXC-1), has been characterized as a neutrophil-attracting, ELRCXC chemokine with a potency similar to IL-8 (53) that binds specifically to hCXCR2 and to no other known or orphan receptor tested.…”

Section: Potential Mechanisms Of Cmv-induced Cardiac Allograft Vasculmentioning

confidence: 94%

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

Section: Potential Mechanisms Of Cmv-induced Cardiac Allograft Vasculmentioning

confidence: 94%

The Role of Viruses in Cardiac Allograft Vasculopathy

Valantine

2004

American Journal of Transplantation

View full text Add to dashboard Cite

show abstract

“…In vivo and in vitro, HCMV infects all of these cell types, and aside from immunologic clearance, viral infection modifies many of the host cellular functions that promote tissue repair. For example, CMV infection resulting in acceleration of CR is the increase in the host immune response to the allograft and the virus resulting in recruitment of inflammatory cells, and inflammatory effectors such as chemokines and cytokines including IFN-γ, TNF-α, IL-4, IL-18, RANTES, MCP-1, MIP-1α, IL-8, and IP-10 (Almeida et al 1994;Almeida-Porada et al 1997;Vieira et al 1998;Humar et al 1999;Streblow et al 1999;Streblow et al 2003;Vliegen et al 2004). CMV also encodes CC and CXC chemokine homologues (Beisser et al, this volume) that recruit a multitude of host cellular infiltrates (Sparer et al 2004;Noda et al 2006).…”

Section: In Vitro Models Of Hcmv Mediated Wound Healing and Angiogenesismentioning

confidence: 99%

Mechanisms of Cytomegalovirus-Accelerated Vascular Disease: Induction of Paracrine Factors That Promote Angiogenesis and Wound Healing

Streblow

Dumortier

Moses

et al. 2008

Current Topics in Microbiology and Immunology

108

View full text Add to dashboard Cite

Human cytomegalovirus (HCMV) is associated with the acceleration of a number of vascular diseases such as atherosclerosis, restenosis, and transplant vascular sclerosis (TVS). All of these diseases are the result of either mechanical or immune-mediated injury followed by inflammation and subsequent smooth muscle cell (SMC) migration from the vessel media to the intima and proliferation that culminates in vessel narrowing. A number of epidemiological and animal studies have demonstrated that CMV significantly accelerates TVS and chronic rejection (CR) in solid organ allografts. In addition, treatment of human recipients and animals alike with the antiviral drug ganciclovir results in prolonged survival of the allograft indicating that CMV replication is a requirement for acceleration of disease. However, although virus persists in the allograft throughout the course of disease, the number of directly infected cells does not account for the global effects that the virus has on the acceleration of TVS and CR. Recent investigations of up-and down-regulated cellular genes in infected allografts in comparison to native heart has demonstrated that Rat-CMV (RCMV) up-regulates genes involved in wound healing (WH) and angiogenesis (AG). Consistent with this result, we have found that supernatants from HCMV infected cells (HCMV secretome) induce WH and AG using in vitro models. Taken together these findings suggest that one mechanism for HCMV acceleration of TVS is mediated through induction of secreted cytokines and growth factors from virus-infected cells that promote WH and AG in the allograft, resulting in the acceleration of TVS. We review here the ability of CMV infection to alter the local environment by producing cellular factors that act in a paracrine fashion to enhance WH and AG processes associated with the development of vascular disease, which accelerates chronic allograft rejection.

show abstract

“…One important indirect effect of CMV infection resulting in acceleration of CR is the increase in the host immune response to the allograft and the virus resulting in recruitment of inflammatory cells, and inflammatory effectors such as chemokines and cytokines including IFN-γ, TNF-α, IL-4, IL-18, RANTES, MCP-1, MIP-1α, IL-8, and IP-10 [27,28,31,[33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52]. CMV also encodes CC and CXC chemokine homologues that recruit a multitude of host cellular infiltrates [53,54].…”

Section: Mechanisms Of CMV Accelerated Tvs and Chronic Rejectionmentioning

confidence: 99%

“…In addition, CMV modifies a number of cellular functions that then mediate viral spread, persistence and immune evasion. For instance, CMV also induces cellular factors involved in angiogenesis and wound repair processes including adhesion molecules (ICAM-1, VCAM-1, VAP-1, and E-selectin,) and growth factors and receptors (TGF-β, PDGF-AA, VEGF, and PDGFR) [37,52,[55][56][57][58][59][60][61][62][63][64][65]. In addition, increased matrix metalloproteinase (MMP)-2 activity is observed in HCMV infected cells in conjunction with a reduction in matrix gene expression, resulting in a malleability to SMC migration, an alteration in vessel remodeling which promotes a vasculopathy [49,50].…”

Section: Mechanisms Of CMV Accelerated Tvs and Chronic Rejectionmentioning

confidence: 99%

“…HCMV infection of rat SMC increases the expression of PDGF receptor, which may induce both proliferation and migration of these cells [61]. It has been proposed that HCMV infection enhances SMC migration preferentially towards sites of vascular injury due to expression in infected SMC of the virally-encoded chemokine receptor US28 and the binding of the CC-chemokines RANTES or MCP-1 [37]. The resulting SMC accumulation in the vessel intima leads to neointimal hyperplasia and vessel narrowing.…”

Section: Mechanisms Of CMV Accelerated Tvs and Chronic Rejectionmentioning

confidence: 99%

See 1 more Smart Citation

Acceleration of allograft failure by cytomegalovirus

Streblow

Orloff

Nelson

2007

Current Opinion in Immunology

121

View full text Add to dashboard Cite

SummaryA number of human herpes viruses are important opportunistic pathogens that have been associated with increased morbidity and mortality in transplant recipients including human cytomegalovirus (HCMV), HHV6, HHV7, HHV8 as well as HSV-1, VZV. However, HCMV has been linked both epidemiologically and through the use of animal models to the acceleration of acute and chronic allograft rejection. This review will cover the pathophysiology, epidemiology and mechanisms of CMV-associated disease in the setting of transplantation.

show abstract

The Human Cytomegalovirus Chemokine Receptor US28 Mediates Vascular Smooth Muscle Cell Migration

Cited by 392 publications

References 54 publications

The Role of Viruses in Cardiac Allograft Vasculopathy

The Role of Viruses in Cardiac Allograft Vasculopathy

Mechanisms of Cytomegalovirus-Accelerated Vascular Disease: Induction of Paracrine Factors That Promote Angiogenesis and Wound Healing

Acceleration of allograft failure by cytomegalovirus

Contact Info

Product

Resources

About