Signaling Activities of Gammaherpesvirus Membrane Proteins

Damania, Blossom; Choi, Joong Kook; Jung, Jae U.

doi:10.1128/jvi.74.4.1593-1601.2000

Cited by 54 publications

(35 citation statements)

References 139 publications

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“…Thus, it is not surprising that viruses, including EBV, often utilize this signalling pathway to prolong the lifespan and promote the transformation of infected cells (reviewed by Damania et al, 2000;Santoro et al, 2003). The EBV-encoded LMP1 is the major effector of EBV-induced NF-kB and this activity appears to be responsible for many of its pleiotropic in vitro effects, including the ability to transform fibroblast cell lines, to upregulate a number of antiapoptotic proteins and to induce the expression of angiogenic factors and cell surface markers associated with motility and invasion (Cahir-McFarland et al, 1999;Eliopoulos and Young, 2001).…”

Section: Discussionmentioning

confidence: 99%

Epstein–Barr virus-encoded latent infection membrane protein 1 regulates the processing of p100 NF-κB2 to p52 via an IKKγ/NEMO-independent signalling pathway

et al. 2003

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The oncogenic Epstein-Barr virus (EBV)-encoded latent infection membrane protein 1 (LMP1) constitutively activates the 'canonical' NF-jB pathway that involves the phosphorylation and degradation of IjBa downstream of the IjB kinases (IKKs). In this study, we show that LMP1 also promotes the proteasome-mediated proteolysis of p100 NF-jB2 resulting in the generation of active p52, which translocates to the nucleus in complex with the p65 and RelB NF-jB subunits. LMP1-induced NF-jB transactivation is reduced in nf-kb2 À/À mouse embryo fibroblasts, suggesting that p100 processing contributes to LMP1-mediated NF-jB transcriptional effects. This pathway is likely to operate in vivo, as the expression of LMP1 in primary EBV-positive Hodgkin's lymphoma and nasopharyngeal carcinoma biopsies correlates with the nuclear accumulation of p52. Interestingly, while the ability of LMP1 to activate the canonical NF-jB pathway is impaired in cells lacking IKKc/NEMO, the regulatory subunit of the IKK complex, p100 processing remains unaffected. As a result, nuclear translocation of p52, but not p65, occurs in the absence of IKKc. These data point to the existence of a novel signalling pathway that regulates NF-jB in LMP1-expressing cells, and may thereby play a role in both oncogenic transformation and the establishment of persistent EBV infection.

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Section: Discussionmentioning

confidence: 99%

Epstein–Barr virus-encoded latent infection membrane protein 1 regulates the processing of p100 NF-κB2 to p52 via an IKKγ/NEMO-independent signalling pathway

et al. 2003

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“…Gammaherpesviruses are a group of DNA tumor viruses that form a subfamily of the Herpesviridae (Chang et al 1994;Damania et al 2000;Ganem 1997;Roizman and Pellett 2001). The two known human members of the subfamily, Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV), are significant pathogens associated with lymphomas and other malignancies (Carbone 2003;Chang et al 1994;Damania et al 2000;Damania et al 1999;Mueller 1999).…”

Section: Introductionmentioning

confidence: 99%

“…The two known human members of the subfamily, Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV), are significant pathogens associated with lymphomas and other malignancies (Carbone 2003;Chang et al 1994;Damania et al 2000;Damania et al 1999;Mueller 1999). Along with herpes simplex virus-1 (HSV-1) --the prototypic alphaherpesvirus that causes cold sores, and human cytomegalovirus (HCMV) --a betaherpesvirus that is a leading cause of birth defects, gammaherpesviruses have a characteristic multilayered architecture.…”

Section: Introductionmentioning

confidence: 99%

Unique structures in a tumor herpesvirus revealed by cryo-electron tomography and microscopy

Dai

Jia

Bortz

et al. 2008

Journal of Structural Biology

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Gammaherpesviruses, including the human pathogens Epstein-Barr virus and Kaposi's sarcomaassociated herpesvirus, are causative agents of lymphomas and other malignancies. The structural characterization of these viruses has been limited due to difficulties in obtaining adequate amount of virion particles. Here we report the first three-dimensional structural characterization of a whole gammaherpesvirus virion by an emerging integrated approach of the technique of cryo-electron tomography combined with single-particle cryo-electron microscopy, using murine gammaherpesvirus-68 (MHV-68) as a model system. We found that the MHV-68 virion consists of distinctive envelope and tegument compartments, and a highly conserved nucleocapsid. Two layers of tegument are identified: an inner tegument layer tethered to the underlying capsid and an outer, flexible tegument layer conforming to the overlying, pleomorphic envelope, consistent with the sequential viral tegumentation process inside host cells. Surprisingly, comparison of the MHV-68 virion and capsid reconstructions shows that the interactions between the capsid and inner tegument proteins are completely different from those observed in alpha and betaherpesviruses. These observations support the notion that inner layer tegument across different subfamilies of herpesviruses have evolved significantly to confer specific characteristics related to viral-host interactions, in contrast to a highly conserved capsid for genome encapsidation and protection.

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“…A striking feature of gammaherpesviruses is that they contain a distinct open reading frame at the end of their genome; each of these open reading frames has characteristic transforming ability (11,12,26). These include the Epstein-Barr virus (EBV) latent membrane protein 1 (LMP-1) and HVS STP.…”

Section: Discussionmentioning

confidence: 99%

Activation of Stat3 Transcription Factor by Herpesvirus Saimiri STP-A Oncoprotein

Chung

Cho

García

et al. 2004

J Virol

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Signaling Activities of Gammaherpesvirus Membrane Proteins

Cited by 54 publications

References 139 publications

Epstein–Barr virus-encoded latent infection membrane protein 1 regulates the processing of p100 NF-κB2 to p52 via an IKKγ/NEMO-independent signalling pathway

Epstein–Barr virus-encoded latent infection membrane protein 1 regulates the processing of p100 NF-κB2 to p52 via an IKKγ/NEMO-independent signalling pathway

Unique structures in a tumor herpesvirus revealed by cryo-electron tomography and microscopy

Activation of Stat3 Transcription Factor by Herpesvirus Saimiri STP-A Oncoprotein

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