Alterations in the Expression of ELAM‐1, ICAM‐1 and VCAM‐1 after <i>In Vitro</i> Infection of Endothelial Cells with a Clinical Isolate of Human Cytomegalovirus

Shahgasempour, Shapour; Woodroffe, S. B.; Garnett, Helen M.

doi:10.1111/j.1348-0421.1997.tb01177.x

Cited by 52 publications

(51 citation statements)

References 21 publications

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“…Endothelial cells from diverse vascular beds have different responses, such as altered viral replication and cell adhesion molecule expression, following HCMV infection (17,21,45,48,52,76,80). To examine if HCMV infection of endothelial cells from different origins promoted monocyte migration, we performed migration assays on two additional endothelial cell lines, IHECs and HUVECs, which are microvascular endothelial cells of brain origin and macrovascular endothelial cells of venous origin, respectively.…”

Section: Resultsmentioning

confidence: 99%

Human Cytomegalovirus (HCMV) Infection of Endothelial Cells Promotes Naïve Monocyte Extravasation and Transfer of Productive Virus To Enhance Hematogenous Dissemination of HCMV

Bentz

Jarquin-Pardo

Chan

et al. 2006

J Virol

118

124

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Human cytomegalovirus (HCMV) pathogenesis is dependent on the hematogenous spread of the virus to host tissue. While data suggest that infected monocytes are required for viral dissemination from the blood to the host organs, infected endothelial cells are also thought to contribute to this key step in viral pathogenesis. We show here that HCMV infection of endothelial cells increased the recruitment and transendothelial migration of monocytes. Infection of endothelial cells promoted the increased surface expression of cell adhesion molecules (intercellular cell adhesion molecule 1, vascular cell adhesion molecule 1, E-selectin, and platelet endothelial cell adhesion molecule 1), which were necessary for the recruitment of naïve monocytes to the apical surface of the endothelium and for the migration of these monocytes through the endothelial cell layer. As a mechanism to account for the increased monocyte migration, we showed that HCMV infection of endothelial cells increased the permeability of the endothelium. The cellular changes contributing to the increased permeability and increased naïve monocyte transendothelial migration include the disruption of actin stress fiber formation and the decreased expression of lateral junction proteins (occludin and vascular endothelial cadherin). Finally, we showed that the migrating monocytes were productively infected with the virus, documenting that the virus was transferred to the migrating monocyte during passage through the lateral junctions. Together, our results provide evidence for an active role of the infected endothelium in HCMV dissemination and pathogenesis.Human cytomegalovirus (HCMV) is a betaherpesvirus that establishes a life-long persistent infection (10). In immunocompromised individuals, such as AIDS patients, neonates, and transplant recipients, HCMV infection is associated with significant morbidity and mortality (13,38,56,87). In immunocompetent hosts, HCMV infection is generally asymptomatic, although it can cause mononucleosis (40) and is associated with chronic inflammatory diseases, such as the cardiovascular diseases atherosclerosis and coronary restenosis (1,19,35,46,51,57,59,86,90,107).HCMV pathogenesis is a direct result of viral spread to host organs and the subsequent infection of those organ systems (6,44,54,83). Systemic spread occurs during both asymptomatic and symptomatic infections (93) and is required for HCMV persistence in the host (83). During primary infection, the virus spreads from the initial site of infection to the peripheral blood and then to host organ tissue (6,54,83). In healthy hosts, infection of these organ systems allows for the establishment of the viral persistence needed for viral survival in the infected host and in the general population. In contrast, in immunocompromised hosts, because of the absence of a functional immune response, this same strategy of viral spread would lead to the overt organ disease seen in these individuals (83).The mechanisms of HCMV dissemination remain unclear; however, cells of the ...

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Section: Resultsmentioning

confidence: 99%

Human Cytomegalovirus (HCMV) Infection of Endothelial Cells Promotes Naïve Monocyte Extravasation and Transfer of Productive Virus To Enhance Hematogenous Dissemination of HCMV

Bentz

Jarquin-Pardo

Chan

et al. 2006

J Virol

118

124

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“…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). In addition, CMV modifies a number of other 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) (Shahgasempour et al 1997;Burns et al 1999;Zhou et al 1999;Inkinen et al 2003;Helantera et al 2005;Inkinen et al 2005;Reinhardt et al 2005a;Reinhardt et al 2005b;Helantera et al 2006). 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 (Schaarschmidt et al 1999;Reinhardt 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

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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.

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“…Cytomegalovirus (CMV) has been shown to upregulate intercellular adhesion molecule-1 (ICAM-1), E-selectin, and vascular cell adhesion molecule-1 (VCAM-1). 13,14 HIV-1 infection has been shown to result in upregulation of VCAM-1 and E-selectin. 15 Flavivirus and certain strains of measles virus have also been shown to upregulate ICAM-1 expression.…”

mentioning

confidence: 99%

Infection of Endothelium With E1 ⁻ E4 ⁺ , but Not E1 ⁻ E4 ⁻ , Adenovirus Gene Transfer Vectors Enhances Leukocyte Adhesion and Migration by Modulation of ICAM-1, VCAM-1, CD34, and Chemokine Expression

Rafii

Dias

Meeus

et al. 2001

Circulation Research

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Abstract-Intravascular introduction of replication-deficient adenoviral vectors (Advectors) provides an ideal model of delivery of transgenes for the treatment of various vascular abnormalities. On the basis of the knowledge that Advectors can induce inflammatory responses after intravascular administration, we speculated that cellular activation by Advector infection could directly modulate the endothelial cell (EC) adhesion molecule/chemokine expression repertoire. Infection of human umbilical vein ECs or bone marrow microvascular ECs with an E1 Ϫ E4 ϩ Advector resulted in the upregulation of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and CD34, but not E-selectin, P-selectin, CD36, CD13, CD44, HLA-DR or PECAM. Upregulation of ICAM-1, VCAM-1, and CD34 was apparent 12 hours after infection and persisted for weeks after infection. Selective induction of adhesion molecules was mediated by the presence of the E4 gene in the Advector, because infection of ECs with an E1 Ϫ E4Ϫ Advector had no effect on adhesion molecule expression.

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Alterations in the Expression of ELAM‐1, ICAM‐1 and VCAM‐1 after In Vitro Infection of Endothelial Cells with a Clinical Isolate of Human Cytomegalovirus

Cited by 52 publications

References 21 publications

Human Cytomegalovirus (HCMV) Infection of Endothelial Cells Promotes Naïve Monocyte Extravasation and Transfer of Productive Virus To Enhance Hematogenous Dissemination of HCMV

Human Cytomegalovirus (HCMV) Infection of Endothelial Cells Promotes Naïve Monocyte Extravasation and Transfer of Productive Virus To Enhance Hematogenous Dissemination of HCMV

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

Infection of Endothelium With E1 ⁻ E4 ⁺ , but Not E1 ⁻ E4 ⁻ , Adenovirus Gene Transfer Vectors Enhances Leukocyte Adhesion and Migration by Modulation of ICAM-1, VCAM-1, CD34, and Chemokine Expression

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Alterations in the Expression of ELAM‐1, ICAM‐1 and VCAM‐1 after In Vitro Infection of Endothelial Cells with a Clinical Isolate of Human Cytomegalovirus

Cited by 52 publications

References 21 publications

Human Cytomegalovirus (HCMV) Infection of Endothelial Cells Promotes Naïve Monocyte Extravasation and Transfer of Productive Virus To Enhance Hematogenous Dissemination of HCMV

Human Cytomegalovirus (HCMV) Infection of Endothelial Cells Promotes Naïve Monocyte Extravasation and Transfer of Productive Virus To Enhance Hematogenous Dissemination of HCMV

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

Infection of Endothelium With E1 − E4 + , but Not E1 − E4 − , Adenovirus Gene Transfer Vectors Enhances Leukocyte Adhesion and Migration by Modulation of ICAM-1, VCAM-1, CD34, and Chemokine Expression

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Infection of Endothelium With E1 ⁻ E4 ⁺ , but Not E1 ⁻ E4 ⁻ , Adenovirus Gene Transfer Vectors Enhances Leukocyte Adhesion and Migration by Modulation of ICAM-1, VCAM-1, CD34, and Chemokine Expression