HCMV microinfections in inflammatory diseases and cancer

Söderberg‐Nauclér, Cecilia

doi:10.1016/j.jcv.2007.11.009

Cited by 128 publications

(122 citation statements)

References 43 publications

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“…Unlike KSHV and EBV, the human cytomegalovirus (HCMV) is not considered an oncogenic herpesvirus (5), but it has been suggested to act as an oncomodulator (6). The presence of HCMV proteins has been detected in several malignancies, such as colon cancer (7), malignant glioblastoma (8), and breast cancer (9). Importantly, HCMV preferably infects tumor cells, leading to enhanced cell proliferation, angiogenesis, and resistance to apoptosis (6,10).…”

Section: Introductionmentioning

confidence: 99%

The Human Cytomegalovirus–Encoded Chemokine Receptor US28 Promotes Angiogenesis and Tumor Formation via Cyclooxygenase-2

et al. 2009

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The human cytomegalovirus (HCMV), potentially associated with the development of malignancies, encodes the constitutively active chemokine receptor US28. Previously, we have shown that US28 expression induces an oncogenic phenotype both in vitro and in vivo. Microarray analysis revealed differential expression of genes involved in oncogenic signaling in US28-expressing NIH-3T3 cells. In particular, the expression of cyclooxygenase-2 (COX-2), a key mediator of inflammatory diseases and major determinant in several forms of cancer, was highly up-regulated. US28 induced increases in COX-2 expression via activation of nuclear factor-KB, driving the production of vascular endothelial growth factor. Also, in HCMV-infected cells, US28 contributed to the viral induction of COX-2. Finally, the involvement of COX-2 in US28-mediated tumor formation was evaluated using the COX-2 selective inhibitor Celecoxib. Targeting COX-2 in vivo with Celecoxib led to a marked delay in the onset of tumor formation in nude mice injected with US28-transfected NIH-3T3 cells and a reduction of subsequent growth by repressing the US28-induced angiogenic activity. Hence, the development of HCMV-related proliferative diseases may partially be ascribed to the ability of US28 to activate COX-2.

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Section: Introductionmentioning

confidence: 99%

The Human Cytomegalovirus–Encoded Chemokine Receptor US28 Promotes Angiogenesis and Tumor Formation via Cyclooxygenase-2

et al. 2009

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“…Following primary infection, which is usually benign in immunocompetent individuals, CMV can establish latency in myeloid and endothelial cells and can periodically reactivate to an active infection (3). CMV disease is a major cause of morbidity and mortality in immunosuppressed patients, especially recipients of solid organ or bone marrow transplants, neonates, AIDS patients, cardiovascular disease patients, and the elderly (4)(5)(6). CMV disease is a major medical problem projected to cost a total of $4.4 billion/year (7).…”

mentioning

confidence: 99%

Virion Glycoprotein-Mediated Immune Evasion by Human Cytomegalovirus: a Sticky Virus Makes a Slick Getaway

Gardner

Tortorella

2016

Microbiol Mol Biol Rev

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SUMMARYThe prototypic herpesvirus human cytomegalovirus (CMV) exhibits the extraordinary ability to establish latency and maintain a chronic infection throughout the life of its human host. This is even more remarkable considering the robust adaptive immune response elicited by infection and reactivation from latency. In addition to the ability of CMV to exist in a quiescent latent state, its persistence is enabled by a large repertoire of viral proteins that subvert immune defense mechanisms, such as NK cell activation and major histocompatibility complex antigen presentation, within the cell. However, dissemination outside the cell presents a unique existential challenge to the CMV virion, which is studded with antigenic glycoprotein complexes targeted by a potent neutralizing antibody response. The CMV virion envelope proteins, which are critical mediators of cell attachment and entry, possess various characteristics that can mitigate the humoral immune response and prevent viral clearance. Here we review the CMV glycoprotein complexes crucial for cell attachment and entry and propose inherent properties of these proteins involved in evading the CMV humoral immune response. These include viral glycoprotein polymorphism, epitope competition, Fc receptor-mediated endocytosis, glycan shielding, and cell-to-cell spread. The consequences of CMV virion glycoprotein-mediated immune evasion have a major impact on persistence of the virus in the population, and a comprehensive understanding of these evasion strategies will assist in designing effective CMV biologics and vaccines to limit CMV-associated disease.

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“…After primary infection, HCMV remains lifelong in its host, being able to avoid clearance from the immune system. Whether HCMV persists in a truly latent state (defined as persistence in the absence of detectable infectious virus particles) or in a continuous lowlevel replication state is not clear (2,3). However, the observation that around 10% of CD8 ϩ and CD4 ϩ T cells in the peripheral blood of healthy seropositive persons are committed to anti-HCMV responses (4) argues for continuous restimulation of T cells with antigens produced during phases of viral reactivation or low-grade active replication.…”

mentioning

confidence: 99%

Human Cytomegalovirus Infection of M1 and M2 Macrophages Triggers Inflammation and Autologous T-Cell Proliferation

Bayer

Varani

Wang

et al. 2013

J Virol

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H uman cytomegalovirus (HCMV) (1) is a herpesvirus that persistently infects the majority of the human population. After primary infection, HCMV remains lifelong in its host, being able to avoid clearance from the immune system. Whether HCMV persists in a truly latent state (defined as persistence in the absence of detectable infectious virus particles) or in a continuous lowlevel replication state is not clear (2, 3). However, the observation that around 10% of CD8 ϩ and CD4 ϩ T cells in the peripheral blood of healthy seropositive persons are committed to anti-HCMV responses (4) argues for continuous restimulation of T cells with antigens produced during phases of viral reactivation or low-grade active replication. Antigen recognition and T-cell activation are defined by the tightly regulated interaction between the T-cell receptor (TCR) and antigenic peptides that are presented in the context of class I or class II major histocompatibility complex (MHC) molecules on the surface of antigen-presenting cells (APC). A number of studies have shown that the most potent APC, i.e., dendritic cells (DC), are severely impaired by HCMV in their antigen presentation, migration, and T-cell activation capabilities (reviewed in reference 5). How APC that are altered in their function can trigger and maintain a massive HCMVspecific T-cell repertoire is difficult to explain. Due to their dual nature of being permissive to HCMV infection (6-9) and being professional APC (10), macrophages (M) would represent the ideal site for antigen production, processing, and presentation to the adaptive branch of the immune system during HCMV infection.We and others have shown that M are highly susceptible to HCMV infection in vitro and that these cells produce viral progeny (11)(12)(13)(14)(15). Nevertheless, the majority of previous studies did not take into account that, in the context of immunity and inflammation, M acquire different activation states. For the sake of simplicity, M have been classified along what could be viewed as a linear scale, in which M1 M represent one extreme and M2 M the other (16). In this classification, the M1 designation refers to classically activated M, namely, cells that are capable of sustaining the immune response to pathogens through release of proinflammatory factors as well as efficient antigen presentation and T-cell stimulation. The M2 designation refers to alternatively activated M, namely, a very heterogeneous group of cells contributing to resolution of inflammation, tissue repair, extracellular matrix remodeling, and pathogen scavenging. Recent evidence indicates different susceptibilities of M1 and M2 M to HCMV infection (17,18). Nevertheless, the course of HCMV infection in these two types of M as well as the M-specific contribution to the adaptive immune response against HCMV still remains elusive.In this study, we addressed how M polarization defines HCMV susceptibility and how HCMV infection modifies M activation. We also determined the capability of HCMV-infected M to present antigen to ...

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HCMV microinfections in inflammatory diseases and cancer

Cited by 128 publications

References 43 publications

The Human Cytomegalovirus–Encoded Chemokine Receptor US28 Promotes Angiogenesis and Tumor Formation via Cyclooxygenase-2

The Human Cytomegalovirus–Encoded Chemokine Receptor US28 Promotes Angiogenesis and Tumor Formation via Cyclooxygenase-2

Virion Glycoprotein-Mediated Immune Evasion by Human Cytomegalovirus: a Sticky Virus Makes a Slick Getaway

Human Cytomegalovirus Infection of M1 and M2 Macrophages Triggers Inflammation and Autologous T-Cell Proliferation

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