Reversal of the measles virus-mediated increase of phosphorylating activity in persistently infected mouse neuroblastoma cells by anti-measles virus antibodies

Segev, Yael; Rager-Zisman, Bracha; Isakov, Noah; Schneider‐Schaulies, Sibylle; Meulen, Volker ter; Udem, Stephen A.; Segal, Shraga; Wolfson, Marina

doi:10.1099/0022-1317-75-4-819

Cited by 10 publications

(4 citation statements)

References 65 publications

(47 reference statements)

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“…Involvement of cellular protein kinases in HSV and other viral infections has been reported; UL34 product, the target of HSV-1 protein kinase encoded by US3, has been suggested to inhibit a kinase or activate a phosphatase in infected cells [30]; varicella-zoster virus gpI was shown to be phosphorylated by mammalian casein kinase II and casein kinase I [16]; protein kinase C-mediated phosphorylation is required for the maturation of infectious measles particles [31]. Protein kinases, irrespective of their viral or cellular origin, should play an important role in virus infection.…”

Section: Discussionmentioning

confidence: 99%

Inhibitory effect of tyrphostin on the replication of herpes simplex virus type 1

Yura

Kusaka

Kondo

et al. 1995

Archives of Virology

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Tyrphostins 9 and 47, inhibitors of protein-tyrosine kinase, inhibited the replication of herpes simplex virus type 1 (HSV-1), whereas tyrophostin 1, which does not inhibit protein-tyrosine kinase, did not affect the replication of HSV-1. The inhibitory effect of tyrphostin 9 was more potent than that of tyrphostin 47, and the IC50 of tyrphostin 9 was 40 nM. Sodium orthovanadate, an inhibitor of protein phosphotyrosine phosphatase, increased HSV-1 plaque formation and its effect was partly reversed by tyrphostin 9. The phosphorylation of viral phosphoproteins was decreased by tyrphostin 9 in a dose-dependent manner, but the tyrphostin 9-induced reduction of protein synthesis was not dose-dependent. At the late stage of infection, tyrosine phosphorylation was demonstrated in HSV-1 phosphoproteins. These results indicate that protein-tyrosine kinase is involved in the replication of HSV-1 and that tyrphostin can inhibit the synthesis and post-translational phosphorylation of the viral proteins.

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Section: Discussionmentioning

confidence: 99%

Inhibitory effect of tyrphostin on the replication of herpes simplex virus type 1

Yura

Kusaka

Kondo

et al. 1995

Archives of Virology

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“…Defective measles matrix (M) protein has been recovered in some SSPE cases and was suggested as a possible underlying mechanism for persistence (11,15,20). Our previous research also demonstrated that there is significantly less viral budding in persistent versus acute MV infection of murine neuroblastoma cell lines and that this is not due to decreased viral protein synthesis, which is unimpaired (22,25). Viral budding in MV infection involves the incorporation of envelope proteins into the host cell membrane (5).…”

mentioning

confidence: 99%

Impaired Cholesterol Biosynthesis in a Neuronal Cell Line Persistently Infected with Measles Virus

Robinzon

Dafa-Berger²,

Dyer

et al. 2009

J Virol

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Measles virus remains a substantial cause of morbidity and mortality, producing acute infection with a potential for development of viral persistence. To study the events underlying acute and persistent measles virus infection, we performed a global transcriptional analysis on murine neuroblastoma cells that were acutely or persistently infected with measles virus. In general, we found that acute infection induced significantly more gene expression changes than did persistent infection. A functional enrichment analysis to identify which host pathways were perturbed during each of these infections identified several pathways related to cholesterol biosynthesis, including cholesterol metabolic processes, hydroxymethylglutaryl-coenzyme A (CoA) reductase activity, and acetyl-CoA C-acetyltransferase activity. We also found that measles virus colocalized to lipid rafts in both acute and persistent infection models and that the majority of genes associated with cholesterol synthesis were downregulated in persistent infection relative to acute infection, suggesting a possible link with the defective viral budding in persistent infection. Further, we found that pharmacological inhibition of cholesterol synthesis resulted in the inhibition of viral budding during acute infection. In summary, persistent measles viral infection was associated with decreased cholesterol synthesis, a lower abundance of cholesterol and lipid rafts in the cell membrane, and inhibition of giant-cell formation and release of viral progeny.Measles virus (MV) remains a significant health burden, claiming 450,000 lives worldwide every year, and most of the deaths occur in children (35). MV is the etiological agent of both acute measles infection and subacute sclerosing panencephalitis (SSPE), a rare and devastating persistent infection of the central nervous system (7,8,12). MV is typically highly cytolytic, resulting in an acute infection that confers lifelong immunity. The reasons and underlying mechanisms of transformation into a persistent infection in some individuals remain unknown, and the pathological implications of such an infection are controversial.Although no mechanism for the transformation from acute to persistent infection has been established, partial explanations have been proposed. Defective measles matrix (M) protein has been recovered in some SSPE cases and was suggested as a possible underlying mechanism for persistence (11,15,20). Our previous research also demonstrated that there is significantly less viral budding in persistent versus acute MV infection of murine neuroblastoma cell lines and that this is not due to decreased viral protein synthesis, which is unimpaired (22,25). Viral budding in MV infection involves the incorporation of envelope proteins into the host cell membrane (5). This has been recently shown to occur in lipid rafts-cholesterol-rich domains in the cellular membrane (17,19,21,33).In this study, we used microarray analysis to compare gene expression during acute and persistent infection with MV and to id...

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“…Total phosphorylation and protein kinase C activity decrease to levels comparable to those in uninfected cells and gradually return to elevated levels characteristic of VOL. 69, 1995 MV SUPPRESSION BY NONCYTOLYTIC ANTIBODY 739 on July 10, 2020 by guest http://jvi.asm.org/ infected cells when antibody is removed (39). Therefore, signal transduction pathways are likely to be important in the noncytolytic control of viral infection by antibody.…”

Section: Discussionmentioning

confidence: 99%

Suppression of measles virus expression by noncytolytic antibody in an immortalized macrophage cell line

Goldman

O'Bryan

Buckthal

et al. 1995

J Virol

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Immune regulation of measles virus (MV) expression was studied in a persistently infected mouse macrophage cell line. Synthesis of both membrane-associated and internal MV antigens was suppressed when infected macrophages were treated with polyclonal rabbit anti-MV antibody that was specific for MV proteins. Persistently infected macrophages were treated for 3, 5, or 7 days with increasing doses of anti-MV antibody. All MV proteins were down-regulated 2 days after treatment was terminated. One week after treatment was terminated, down-regulation was still evident but to a lesser degree. MV protein synthesis was suppressed whether or not complement components were inactivated by heating all serum supplements and antibodies. However, when complement was active, cell lysis accounted for some of the reduced MV protein synthesis. When lytic destruction of infected cells by antibody and complement was prevented by inactivation of complement, antibody alone reduced the cellular synthesis of viral proteins by noncytolytic mechanisms. The absence of cell death in the absence of complement was confirmed by the lack of 51Cr release from labeled cells, the lack of reduction in cell number, and the lack of a decrease in total protein synthesis when radiolabeled infected cells were treated with antibody. It is noteworthy that low doses of antibody were optimal for suppression in the longer-term experiments and did not cause lysis, even in the presence of active complement. Since infected macrophages disseminate virus in measles infection, noncytolytic regulation of these cells by antibody may supplement viral clearance by cytolytic T cells and other immune mechanisms.

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Reversal of the measles virus-mediated increase of phosphorylating activity in persistently infected mouse neuroblastoma cells by anti-measles virus antibodies

Abstract: H-7). These results demonstrate that measles virus induces elevation in cellular phosphorylation which is essential for measles virus production.

Cited by 10 publications

References 65 publications

Inhibitory effect of tyrphostin on the replication of herpes simplex virus type 1

Inhibitory effect of tyrphostin on the replication of herpes simplex virus type 1

Impaired Cholesterol Biosynthesis in a Neuronal Cell Line Persistently Infected with Measles Virus

Suppression of measles virus expression by noncytolytic antibody in an immortalized macrophage cell line

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