Varicella-zoster virus open reading frame 61 protein is functionally homologous to herpes simplex virus type 1 ICP0

Moriuchi, Hiroyuki; Moriuchi, Masako; Smith, Holly A.; Straus, Stephen E.; Cohen, Jeffrey I.

doi:10.1128/jvi.66.12.7303-7308.1992

Cited by 79 publications

(44 citation statements)

References 39 publications

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“…The fact that this factor has to be expressed before it can perform its activities corresponds with the time course of JNK/SAPK and p38/MAPK phosphorylation described here and recently [Rahaus et al, 2004]. Moriuchi et al [1992] demonstrated a reduction of viral replication when a MeWo cell line expressing VZV ORF61 was infected with HSV strain KOS. Our data demonstrate that the VZV replication is also repressed in MeWo/61 cells.…”

Section: Discussionsupporting

confidence: 76%

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ORF61 protein of Varicella-zoster virus influences JNK/SAPK and p38/MAPK phosphorylation

2005

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Recently, it was demonstrated that the Varicella-zoster virus (VZV) infection led to an activation of MAP kinases. The viral protein encoded by ORF61 is a major effector of JNK/SAPK and p38/MAPK phosphorylation. ORF61 shows homology to HSV-1 ICP0, a multifunctional protein that influences the activity of c-Jun in infected cells. Stable expression of ORF61 in a MeWo derived cell line gave rise to two specific effects: (i) a major decrease of VZV replication and (ii) a strongly elevated basal JNK/SAPK phosphorylation but a reduced p38/MAPK phosphorylation, which were both altered following infection. A dose-dependent inhibition of JNK/SAPK in MeWo/61 cells resulted in a step-by-step increase of VZV replication. These findings indicate (i) that ORF61 is responsible for the elevated JNK/SAPK phosphorylation and (ii) that the VZV replication and the JNK/SAPK phosphorylation are related inversely. Compared to MeWo cells, the basal phosphorylation of downstream targets c-Jun and ATF-2 was reduced following ORF61 expression but restored after infection. Subsequent cascades to induce inflammatory responses were activated insignificantly; cascades to activate apoptotic events also remained silent. These data point towards an important role of ORF61 in the fine-regulation of activation of the MAPK pathways and their downstream targets to optimize the availability of cellular factors involved in VZV gene expression.

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Section: Discussionsupporting

confidence: 76%

“…VZV deleted in ORF 61 is impaired for replication in vivo, but can be complemented [Cohen and Nguyen, 1998]. Due to its homologies to HSV ICP0, VZV ORF61 is also able to complement a herpes simplex-virus type 1 (HSV-1) ICP0 mutant [Moriuchi et al, 1992].…”

Section: Introductionmentioning

confidence: 99%

ORF61 protein of Varicella-zoster virus influences JNK/SAPK and p38/MAPK phosphorylation

2005

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“…Northern blot analysis was performed as described previously (32). Probes specific to the CXCR4 or glyceraldehyde-3-phosphate dehydrogenase gene were prepared as described previously (29).…”

Section: Northern Blot Analysismentioning

confidence: 99%

Promonocytic U937 subclones expressing CD4 and CXCR4 are resistant to infection with and cell-to-cell fusion by T-cell-tropic human immunodeficiency virus type 1

Moriuchi

Arthos

et al. 1997

J Virol

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Different strains of human immunodeficiency virus type 1 (HIV-1) vary markedly in the ability to infect cells of the monocyte/macrophage (M/M) lineage. M/M are generally resistant to infection with T-cell-tropic (T-tropic) strains of HIV-1. Recently, the chemokine receptors CCR5 and CXCR4 were identified as cofactors for fusion/entry of macrophage-and T-tropic strains of HIV-1, respectively. To investigate the mechanisms of resistance of M/M to T-tropic HIV-1 infection, we examined a number of subclones of the U937 promonocytic cell line. We found that certain subclones of U937 (plus clones) could, while others (minus clones) could not, support replication of T-tropic strains of HIV-1. We demonstrate that (i) both minus and plus clones support HIV-1 replication when transfected with an infectious molecular cDNA clone of a T-tropic HIV-1; (ii) minus clones do not, but plus clones do, efficiently support fusion with cells expressing HIV-1 IIIB Env; (iii) both plus and minus clones (with the exception of one clone) express physiologically functional CXCR4 protein as well as CD4 on the cell surface; (iv) introduction of CXCR4 into the CXCR4-negative clone does not restore fusogenicity with or susceptibility to T-tropic HIV -1; and (v) a ligand (stromal cell-derived factor 1) for or a monoclonal antibody (12G5) to CXCR4 does not effectively inhibit HIV-mediated cell-to-cell fusion of U937 cells. These data indicate that resistance to T-tropic HIV-1 infection of U937 minus clones occurs at fusion/ entry events and that expression of functional CXCR4 and CD4 is not a sole determinant for susceptibility to T-tropic HIV-1 infection; furthermore, they suggest that other factors are positively or negatively involved in HIV-mediated cell-to-cell fusion in U937 promonocytic cells.

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“…ORF61 encodes a 62-to 66-kDa phosphoprotein (45), which is highly homologous to herpes simplex virus 1 (HSV-1) ICP0 in the RING finger domain and can partially complement the function of ICP0 in ICP0-null HSV-1 (28). Both proteins exhibit regulatory functions, but the difference between them is that ORF61 has either a transactivated or repressive function (16,31), while ICP0 mostly shows transcriptional activation (12,14).…”

mentioning

confidence: 99%

Varicella-Zoster Virus Immediate-Early Protein ORF61 Abrogates the IRF3-Mediated Innate Immune Response through Degradation of Activated IRF3

Zhu

Zheng

Xing

et al. 2011

J Virol

116

111

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Varicella-zoster virus (VZV) infection of differentiated cells within the host and establishment of latency likely requires evasion of innate immunity and limits secretion of antiviral cytokines. Here we report that its immediate-early protein ORF61 antagonizes the beta interferon (IFN-␤) pathway. VZV infection down-mod-Varicella-zoster virus (VZV) is ubiquitous in most of the population worldwide and is an alphaherpesvirus restricted to humans. Primary VZV infection begins with inoculation of the respiratory mucosa, followed by cell-associated viremia and the rash of chickenpox. During primary infection, the virus establishes latency in sensory ganglia and can subsequently reactivate to cause shingles (herpes zoster) (3). The VZV genome contains one copy of linear double-strand DNA approximately 125 kb in length and encodes about 70 unique proteins. Similar to other alphaherpesviruses, the expression of VZV genes is assorted temporally into three categories-immediate-early (IE), early (E), and late (L)-and the IE proteins usually play critical roles during VZV life cycles (29).ORF61 encodes a 62-to 66-kDa phosphoprotein (45), which is highly homologous to herpes simplex virus 1 (HSV-1) ICP0 in the RING finger domain and can partially complement the function of ICP0 in ICP0-null HSV-1 (28). Both proteins exhibit regulatory functions, but the difference between them is that ORF61 has either a transactivated or repressive function (16, 31), while ICP0 mostly shows transcriptional activation (12,14). Although ICP0 can inhibit the innate immunity pathway at many levels, such as IRF3 and PML (13,26), little is known about the function of ORF61 in interrupting the innate immunity.The innate immune system is an ancient and nonspecific system that provides the first line of defense against infection. One of the most effective innate antiviral responses is the production of alpha/beta interferon (IFN-␣/␤) and the subsequent induction of interferon-stimulated genes (ISGs) (38). Previous studies have demonstrated that VZV infection stimulates innate immune responses mainly by the production of IFN-␣ and IFN-␥ (1, 2, 27), while IFN-␤ is not detected in serum of VZV-infected patients. This might be explained by the evidence provided by one group that the production of IFN-␤ may be blocked by ORF62 during VZV infection (40).Increasing evidence has shown that ICP0 possesses various antagonistic functions against the host innate immune system

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Varicella-zoster virus open reading frame 61 protein is functionally homologous to herpes simplex virus type 1 ICP0

Cited by 79 publications

References 39 publications

ORF61 protein of Varicella-zoster virus influences JNK/SAPK and p38/MAPK phosphorylation

ORF61 protein of Varicella-zoster virus influences JNK/SAPK and p38/MAPK phosphorylation

Promonocytic U937 subclones expressing CD4 and CXCR4 are resistant to infection with and cell-to-cell fusion by T-cell-tropic human immunodeficiency virus type 1

Varicella-Zoster Virus Immediate-Early Protein ORF61 Abrogates the IRF3-Mediated Innate Immune Response through Degradation of Activated IRF3

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