Cytomegalovirus Type Cytopathic Changes in Spontaneously Degenerating Human Embryonic Cell Cultures

Dioşi, P; Babuşceac, Livia; David, C. Montefiori

doi:10.1038/214419a0

Cited by 7 publications

(3 citation statements)

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“…Integrin expression patterns on HCMV susceptible cells (13,27,28), HCMV-induced cellular morphological changes (12), and overlapping signaling capabilities (9-11) suggest that integrins may be involved in HCMV entry. Because all viruses known to use integrins as entry receptors have been shown to do so by ECM protein mimicry, we inspected all HCMV structural glycoproteins for the integrin-binding sequences LDV, DGE, RGD, NGR, RRETAWA, REDV, SDGR, YIGSR, YIGSE, RGES, RSGIY, RSGD, DRDE, and SRYD by using DNASTAR software (DNASTAR, Madison, WI).…”

Section: The Gb Disintegrin-like Domain Is Highly Conserved Throughoutmentioning

confidence: 99%

“…Gross morphological changes consistent with cytoskeletal remodeling have been observed in response to HCMV for some time (12). To specifically examine CMV-induced cytoskeletal rearrangements and cellular morphological changes, fibroblasts were infected with KSHV, a virus known to enter cells in an integrin-dependent manner and induce cytoskeletal rearrangements, or a virus that does not (vesicular stromatitus virus) (33).…”

Section: Hcmv Uses Integrins At a Postattachment Stage During The Entrymentioning

confidence: 99%

“…Host cells respond to HCMV infection by activating numerous signal transduction pathways including initiating Ca 2ϩ influx at the cell membrane, as well as activating phospolipases C and A2, mitogen-activated protein kinase, p38, NF-B, and SP-1 (10,11). HCMV also induces a distinct cytopathology, with cells rounding 30-60 min after viral challenge corresponding to the entry event (12).…”

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confidence: 99%

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Cellular integrins function as entry receptors for human cytomegalovirus via a highly conserved disintegrin-like domain

Feire

Koss

Compton

2004

Proc. Natl. Acad. Sci. U.S.A.

292

301

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Human cytomegalovirus (HCMV) is capable of manifesting disease in nearly every organ system in immunocompromised patients. This broad pathogenic tropism correlates with the ability of the virus to infect all tested vertebrate cell types in vitro, a characteristic that has made receptor identification extremely difficult. During virus entry, HCMV induces cellular morphological changes and signaling cascades consistent with engagement of cellular integrins; however, HCMV structural proteins do not possess the widely used RGD integrin-binding motif. We identified an integrinbinding disintegrin-like domain within HCMV envelope glycoprotein B, a protein required for virus entry and fusion throughout the Herpesviridae. Accepted receptor criteria are met through the use of function-blocking integrin Abs, ␤1 integrin knockout mouse fibroblasts, and glycoprotein B disintegrin-like peptides, all of which support a critical role for ␣2␤1, ␣6␤1, and ␣V␤3 integrins as HCMV entry receptors and signaling mediators acting during the penetration stage of the entry pathway. Strikingly, the glycoprotein B disintegrin-like domain is conserved in many human and animal herpesviruses, suggesting that integrins may support entry across this medically important virus family.H uman cytomegalovirus (HCMV) is a member of the medically significant Herpesviridae family of viruses. Herpesviruses establish a life-long relationship with their hosts and can manifest disease in an opportunistic manner. HCMV is the most common viral cause of congenital birth defects and is responsible for significant morbidity and mortality in immunocompromised patients, including AIDS patients and organ transplant recipients (1, 2). A notable feature of HCMV pathogenesis is its exceptionally broad tissue tropism. HCMV is capable of manifesting disease in most organ systems and tissue types, which directly correlates with its ability to infect fibroblasts, endothelial cells, epithelial cells, monocytes͞macrophages, smooth muscle cells, stromal cells, neuronal cells, neutrophils, and hepatocytes (3, 4). In vitro entry into target cells is equally promiscuous since HCMV is able to bind, penetrate, and initiate replication in all tested vertebrate cell types (5). HCMV host cell entry begins with a required tethering step to cell surface heparan sulfate proteoglycans (HSPGs) (6). After HSPG binding, the virus transitions to a more stable docking step by engaging unidentified protein receptors (7), all of which lead to fusion at the cell surface (8). Recently, epidermal growth factor receptor (EGFR) was identified as a potential cellular attachment and signaling coreceptor for HCMV, the expression of which correlated with the ability of the virus to initiate gene expression (9). However, EGFR is not expressed on several HCMV permissive cells, such as hematopoetic cell types. Therefore, postattachment entry mediating coreceptors must exist.Many of the physiological consequences associated with HCMV infection are consistent with activation of cellular integrins. Host cel...

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Section: The Gb Disintegrin-like Domain Is Highly Conserved Throughoutmentioning

confidence: 99%

Section: Hcmv Uses Integrins At a Postattachment Stage During The Entrymentioning

confidence: 99%

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confidence: 99%

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