Clinical Coxsackievirus B Isolates Differ from Laboratory Strains in Their Interaction with Two Cell Surface Receptors

Bergelson, Jeffrey M.; Modlin, John F.; Wieland-Alter, Wendy; Cunningham, John J.; Crowell, Richard L.; Finberg, Robert W.

doi:10.1093/infdis/175.3.697

Cited by 93 publications

(89 citation statements)

References 12 publications

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“…18 The infectivity of adenovirus varies in different cells due to CAR or other tumor-associated genes such as CEACAM6. 19,20 In the current study, adenovirus also exhibits differential infectivity on UM cell lines in the form of Ad-GFP expression, which is in concordance with the killing ability of oncolytic adenovirus H101 (Fig. 1).…”

Section: Discussionsupporting

confidence: 84%

Combination of oncolytic adenovirus and dacarbazine enhances antitumor ability against uveal melanoma cells via cell cycle block

Cun¹,

Song²,

Jia³

et al. 2012

Cancer Biology & Therapy

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These authors contributed equally to this work.Keywords: uveal melanoma, oncolytic adenovirus, dacarbazine, combination therapy, cell cycle Uveal melanoma is the most common primary intraocular malignancy in adults; however, current therapeutic modalities, including chemotherapy, have not been successful. Oncolytic viruses serve as an emerging gene therapy tool for cancer treatment because they specifically kill tumor cells while sparing normal cells. The oncolytic virus H101 has been approved by the Chinese State Food and Drug Administration for the treatment of certain malignancies. Unfortunately, the monotherapy of adenovirus has demonstrated limited efficacy in a clinical setting. Thus, novel treatment strategies in which an oncolytic virus is combined with existing chemicals are advancing toward potential clinical use. In this study, we chose the combination of oncolytic virus H101 and the alkylating agent dacarbazine (DTIC) to treat uveal melanoma cells in vitro. Our results demonstrated that the combination exerted a synergistic antitumor effect without enhanced toxicity to normal cells via a type of cell cycle block other than the induction of apoptosis. Further investigation is warranted to elucidate the specific underlying mechanisms of this co-treatment therapy. Our study suggests the virochemo combination therapy is feasible and is a potentially promising approach for the treatment of uveal melanoma.

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Section: Discussionsupporting

confidence: 84%

Combination of oncolytic adenovirus and dacarbazine enhances antitumor ability against uveal melanoma cells via cell cycle block

Cun¹,

Song²,

Jia³

et al. 2012

Cancer Biology & Therapy

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“…It is possible that even in the presence of the antibody, other non-insulin-producing islet cells are infected with CBV-5 in a less cytolytic way. For coxsackie B viruses, two different receptors, HCAR and DAF, have been identified in established cell lines, and especially serotypes 1, 3, 5 are known to use either or both as receptors [24,25,27,52,65]. An important role of HCAR in the development of coxsackievirus diseases has been suggested in recent studies on clinical virus strains characterised after only one passage through primary green monkey kidney cells [27,65].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, a complement regulatory protein, i.e. decay-accelerating factor (DAF), and a protein called human coxsackievirus and adenovirus receptor (HCAR) are used for cellular entry by coxsackieviruses and several EVs [24,25,26,27,28]. However, the function of these receptors in viral entry is not understood in detail and it is possible that additional host factors are needed for complete entry.…”

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confidence: 99%

Enterovirus infection in human pancreatic islet cells, islet tropism in vivo and receptor involvement in cultured islet beta cells

Ylipaasto

Klingel

Lindberg³

et al. 2004

Diabetologia

265

248

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Aims/hypothesis. It is thought that enterovirus infections cause beta-cell damage and contribute to the development of Type 1 diabetes by replicating in the pancreatic islets. We sought evidence for this through autopsy studies and by investigating known enterovirus receptors in cultured human islets. Methods. Autopsy pancreases from 12 newborn infants who died of fulminant coxsackievirus infections and from 65 Type 1 diabetic patients were studied for presence of enteroviral ribonucleic acid by in situ hybridisation. Forty non-diabetic control pancreases were included in the study. The expression and role of receptor candidates in cultured human islets were investigated with receptor-specific antibodies using immunocytochemistry and functional assays. Results. Enterovirus-positive islet cells were found in some of both autopsy specimen collections, but not in control pancreases. No infected cells were seen in exocrine tissue. The cell surface molecules, poliovirus receptor and integrin αvβ 3 , which act as enterovirus receptors in established cell lines, were expressed in beta cells. Antibodies to poliovirus receptor, human coxsackievirus and adenovirus receptor and integrin αvβ 3 protected islets and beta cells from adverse effects of poliovirus, coxsackie B viruses, and several of the arginine-glycine-aspartic acid motifs containing enteroviruses and human parechovirus 1 respectively. No evidence was found for expression of the decay-accelerating factor which acts as a receptor for several isletcell-replicating echoviruses in established cell lines. Conclusions/interpretation. The results show a definite islet-cell tropism of enteroviruses in the human pancreas. Some enteroviruses seem to use previously identified cell surface molecules as receptors in beta cells, whereas the identity of receptors used by other enteroviruses remains unknown. [Diabetologia (2004) 47:225-239]

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“…The essential receptor for CVB is CAR, which mediates both cellular adhesion and internalization of all six serotypes of CVB (6)(7)(8)(9)(10). CAR also facilitates the attachment of adenovirus, although integrins are required for adenovirus internalization (6,11,12).…”

mentioning

confidence: 99%

“…CAR also facilitates the attachment of adenovirus, although integrins are required for adenovirus internalization (6,11,12). CVB binds to CAR with high affinity, and this interaction triggers an irreversible conformational change in the viral capsid that enables viral uncoating (13)(14)(15)(16).…”

mentioning

confidence: 99%

The erythrocyte viral trap: Transgenic expression of viral receptor on erythrocytes attenuates coxsackievirus B infection

Asher

Cerny²,

Finberg³

2005

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

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Viruses rely on attachment to specific cell surface receptors to infect host cells. Selective expression of viral receptors has the potential to attenuate infection of susceptible tissues by redirecting virus to cells that cannot support viral replication. We propose that erythrocytes are an ideal instrument for this strategy, because they are present in vast numbers, permeate every organ, and cannot serve as hosts for viral propagation. To test this hypothesis, we generated a transgenic mouse, termed globin transcription factor 1 (GATA1)-coxsackie and adenovirus receptor (CAR), that expressed the CAR on erythrocytes. Coxsackievirus group B (CVB) adhered to the surface of CAR-expressing erythrocytes and was rendered noninfectious. Upon infection with CVB, GATA1-CAR mice had diminished viremia and reduced viral replication in heart, brain, and liver. Furthermore, when faced with a CVB challenge that was lethal to WT littermates, the survival of GATA1-CAR mice was prolonged, and their ultimate mortality was reduced. The GATA1-CAR mouse model presented here demonstrates that erythrocyte expression of CAR limits CVB pathogenesis. Erythrocytes also may be coated with a variety of receptors by nontransgenic methods, making this a very flexible model for the treatment of infectious diseases in humans.coxsackie and adenovirus receptor ͉ virus receptor V iruses infect cells through attachment to specific host cell membrane receptors. These receptors mediate adhesion of the virus and facilitate its entry into the cell. The expression pattern of the specific receptors for a virus is thus a major determinant of viral tropism. Viruses cannot attack cells that do not bear the appropriate receptors, but they will attempt to infect cells that do, even if those cells are not suitable for viral propagation. If the receptor-expressing cell cannot support replication of the virus, then the virus will spend itself fruitlessly in an attempt to infect it. This idea can be advantageously applied by using selective expression of viral receptors to redirect virus to nonproductive cells, thus protecting susceptible tissues. We propose that erythrocytes are the ideal instrument for this strategy, because these cells are present in vast numbers, permeate every organ, are easily manipulated, are relatively disposable, and cannot serve as hosts for viral replication.Erythrocytes are simultaneously the most numerous and the simplest cells in the body. In their mature form, they lack the nuclei and organelles required to replicate nucleic acids and elaborate proteins. Because viruses depend on the use of the host cell machinery to replicate, erythrocytes are invulnerable to viral infection. The redirection of virus to erythrocytes has the potential to attenuate infection by leading virions to a dead end, leaving fewer infectious particles free to invade susceptible tissues. We hypothesized that the transgenic expression of viral receptor on erythrocytes would overwhelm the virus with decoy targets and thereby limit pathogenesis. Coxsackievirus ...

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Clinical Coxsackievirus B Isolates Differ from Laboratory Strains in Their Interaction with Two Cell Surface Receptors

Cited by 93 publications

References 12 publications

Combination of oncolytic adenovirus and dacarbazine enhances antitumor ability against uveal melanoma cells via cell cycle block

Combination of oncolytic adenovirus and dacarbazine enhances antitumor ability against uveal melanoma cells via cell cycle block

Enterovirus infection in human pancreatic islet cells, islet tropism in vivo and receptor involvement in cultured islet beta cells

The erythrocyte viral trap: Transgenic expression of viral receptor on erythrocytes attenuates coxsackievirus B infection

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