Mechanism of host cell protection from complement in murine cytomegalovirus (CMV) infection: identification of a CMV-responsive element in the CD46 promoter region

Nomura, Midori; Kurita-Taniguchi, Mitsue; Kondo, Kazuhiro; Inoue, Naokazu; Matsumoto, Misako; Yamanishi, Koichi; Okabe, Masaru; Seya, Tsukasa

doi:10.1002/1521-4141(2002010)32:10<2954::aid-immu2954>3.0.co;2-2

Cited by 19 publications

(16 citation statements)

References 42 publications

(53 reference statements)

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“…The putative silencer binding activity was lowest in testicular germ cells, suggesting that low expression of this negative regulator allowed expression in testis [58]. Although the mouse MCP gene is expressed at very low levels in somatic tissues, its expression can be induced by viral infection [59]. Murine cytomegalovirus infection strongly induced MCP expression in fibroblasts and the region responsible was localized near the À750 bp position.…”

Section: Membrane Cofactor Protein (Mcp Cd46)supporting

confidence: 68%

“…Murine cytomegalovirus infection strongly induced MCP expression in fibroblasts and the region responsible was localized near the À750 bp position. Induction of the gene rendered the cells more resistant to complement mediated lysis, suggesting a mechanism for protection of viral infected cells from host complement [59].…”

Section: Membrane Cofactor Protein (Mcp Cd46)mentioning

confidence: 97%

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Transcriptional control of complement receptor gene expression

Martin

2007

Immunol Res

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Immune complement is a critical system in the immune response and protection of host cells from damage by complement is critical during inflammation. The expression of the receptors for the inflammatory anaphylatoxin molecules is also key in immunity. In order to fully appreciate the biology of complement, a basic understanding of the molecular regulation of complement receptor gene expression is critical, yet these kinds of studies are lacking for many genes. Importantly, recent genetic studies have demonstrated that promoter-enhancer polymorphisms can contribute to pathology in diseases such as atypical hemolytic uremic syndrome. This review will focus on what is currently known about the genetic regulation of key protective complement receptors genes including CR1 (CD35), CR2 (CD21), Crry, MCP (CD46), DAF (CD55), and CD59. In addition, the regulation of the anaphylatoxin receptors genes, C3aR and C5aR (CD88) will also be discussed. Since new research continuously uncovers novel functions for these proteins, a greater appreciation of the mechanisms involved in gene regulation will be critical for understanding the biology of these molecules.

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Section: Membrane Cofactor Protein (Mcp Cd46)supporting

confidence: 68%

Section: Membrane Cofactor Protein (Mcp Cd46)mentioning

confidence: 97%

Transcriptional control of complement receptor gene expression

Martin

2007

Immunol Res

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“…The gene expression analysis revealed a number of upregulated cell surface receptors and signaling genes involved in immune functions or stress responses, including CD55, which accelerates the decay of complement proteins and prevents immune system damage to the host cells (41). A more significant number of genes were downregulated.…”

Section: Resultsmentioning

confidence: 56%

Human Cytomegalovirus Infection Causes Premature and Abnormal Differentiation of Human Neural Progenitor Cells

Luo

Hannemann

Kulkarni

et al. 2010

J Virol

101

162

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Congenital human cytomegalovirus (HCMV) infection is a leading cause of birth defects, largely manifested as central nervous system (CNS) disorders. The principal site of manifestations in the mouse model is the fetal brain's neural progenitor cell (NPC)-rich subventricular zone. Our previous human NPC studies found these cells to be fully permissive for HCMV and a useful in vitro model system. In continuing work, we observed that under culture conditions favoring maintenance of multipotency, infection caused NPCs to quickly and abnormally differentiate. This phenotypic change required active viral transcription. Whole-genome expression analysis found rapid downregulation of genes that maintain multipotency and establish NPCs' neural identity. Quantitative PCR, Western blot, and immunofluorescence assays confirmed that the mRNA and protein levels of four hallmark NPC proteins (nestin, doublecortin, sex-determining homeobox 2, and glial fibrillary acidic protein) were decreased by HCMV infection. The decreases required active viral replication and were due, at least in part, to proteasomal degradation. Our results suggest that HCMV infection causes in utero CNS defects by inducing both premature and abnormal differentiation of NPCs.Congenital human cytomegalovirus (HCMV) infection is a leading cause of birth defects, primarily affecting the central nervous system (CNS). Primary infection during pregnancy poses a 30 to 40% risk of intrauterine transmission, with severe adverse outcomes more likely if the infection occurs within the first half of gestation (46). Each year, approximately 1% of all newborns are congenitally infected with HCMV. Approximately 5 to 10% of these infants manifest signs of serious neurological defects at birth, including deafness, mental retardation, blindness, microencephaly, hydrocephalus, and cerebral calcification (2,4,65). In addition, 10 to 15% of congenitally infected infants who are asymptomatic at birth subsequently develop brain disorders such as sensorineural hearing loss (12, 47, 52). Moreover, accumulating evidence suggests that more subtle changes in human brain development, such as autism and language development, may be related to congenital HCMV infection (68,76,77).Although HCMV can infect a wide range of tissues in vivo (61), the fetal brain is the principal site of the deleterious manifestations of infection. It has been suggested that the severity of neuropathological changes and clinical outcomes may be associated with the stage of CNS development at which congenital infection occurs, with early-gestation infections producing more severe outcomes (3, 46). However, the mechanism of HCMV pathogenesis in the developing CNS remains poorly understood. Studies of HCMV in human subjects have obvious limitations; therefore, model systems of both in vitro and in vivo HCMV infections have been devised to provide insights into infection of the developing brain.Congenital infection studies have been performed principally with the mouse model. Studies of mice revealed that very ea...

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“…Herpesviruses in particular are adept at upregulation of complement receptors, particularly those receptors involved in regulation of complement function. Infection with CMV drives upregulated expression of a gene cluster containing CD46 and CD55 (133,160). A CMV-responsive element in the promoter of CD46 is responsible for the increased expression of this complement regulator (133).…”

Section: Viral Evasion and Exploitation Of Complementmentioning

confidence: 99%

“…Infection with CMV drives upregulated expression of a gene cluster containing CD46 and CD55 (133,160). A CMV-responsive element in the promoter of CD46 is responsible for the increased expression of this complement regulator (133). The increased expression of CD55 and CD46 may not only limit complement deposition on virus-infected cells (160), but may also contribute to increased anti-inflammatory signaling in APCs or T cells upon CD46 ligand binding (85,88,99,155).…”

Section: Viral Evasion and Exploitation Of Complementmentioning

confidence: 99%

Role of Complement in Immune Regulation and Its Exploitation by Virus

et al. 2007

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Complement is activated during the early phase of viral infection and promotes destruction of virus particles as well as the initiation of inflammatory responses. Recently, complement and complement receptors have been reported to play an important role in the regulation of innate as well as adaptive immune responses during infection. The regulation of host immune responses by complement involves modulation of dendritic cell activity in addition to direct effects on T-cell function. Intriguingly, many viruses encode homologs of complement regulatory molecules or proteins that interact with complement receptors on antigen-presenting cells and lymphocytes. The evolution of viral mechanisms to alter complement function may augment pathogen persistence and limit immune-mediated tissue destruction. These observations suggest that complement may play an important role in both innate and adaptive immune responses to infection as well as virus-mediated modulation of host immunity.

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Mechanism of host cell protection from complement in murine cytomegalovirus (CMV) infection: identification of a CMV-responsive element in the CD46 promoter region

Cited by 19 publications

References 42 publications

Transcriptional control of complement receptor gene expression

Transcriptional control of complement receptor gene expression

Human Cytomegalovirus Infection Causes Premature and Abnormal Differentiation of Human Neural Progenitor Cells

Role of Complement in Immune Regulation and Its Exploitation by Virus

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