A Systems Biology Approach To Identify the Combination Effects of Human Herpesvirus 8 Genes on NF-κB Activation

Konrad, Andreas; Wies, Effi; Thurau, Mathias; Marquardt, Gaby; Naschberger, Elisabeth; Hentschel, Sonja; Jochmann, Ramona; Schulz, Thomas F.; Erfle, Holger; Brors, Benedikt; Lausen, Berthold; Neipel, Frank; Stürzl, Michael

doi:10.1128/jvi.01512-08

Cited by 48 publications

(68 citation statements)

References 72 publications

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“…1C). This is in accordance with the observation that vFLIP is the strongest NF-B inducer among all KSHV proteins (60). Overexpression of the NF-B-inducing kinase, NIK, also increases interaction of NF-B with DNA (Fig.…”

Section: K15 Induces the Binding Of Nf-b Proteins To Their Target Dnasupporting

confidence: 77%

Activation of NF-κB by the Kaposi's Sarcoma-Associated Herpesvirus K15 Protein Involves Recruitment of the NF-κB-Inducing Kinase, IκB Kinases, and Phosphorylation of p65

Hävemeier

Gramolelli

Pietrek

et al. 2014

J Virol

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Section: K15 Induces the Binding Of Nf-b Proteins To Their Target Dnasupporting

confidence: 77%

Activation of NF-κB by the Kaposi's Sarcoma-Associated Herpesvirus K15 Protein Involves Recruitment of the NF-κB-Inducing Kinase, IκB Kinases, and Phosphorylation of p65

Hävemeier

Gramolelli

Pietrek

et al. 2014

J Virol

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“…The NF-B pathway plays an important role in suppressing the lytic replication of KSHV and MHV68 and promoting latency (107)(108)(109). Several latent KSHV proteins, including full-length LANA and vFLIP, are potent activators of NF-B (109)(110)(111)(112)(113). The ability of cytoplasmic LANA variants to antagonize Mre11-dependent NF-B activation reinforces the notion that cytoplasmic LANA can oppose the effects of full-length LANA.…”

Section: Role Of Cytoplasmic Lana In Antagonizing Innate Immunitysupporting

confidence: 48%

Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen: Replicating and Shielding Viral DNA during Viral Persistence

Weidner-Glunde

Mariggiò

Schulz

2017

J Virol

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Kaposi's sarcoma herpesvirus (KSHV) establishes lifelong latency. The viral latency-associated nuclear antigen (LANA) promotes viral persistence by tethering the viral genome to cellular chromosomes and by participating in latent DNA replication. Recently, the structure of the LANA C-terminal DNA binding domain was solved and new cytoplasmic variants of LANA were discovered. We discuss how these findings contribute to our current view of LANA structure and assembly and of its role during viral persistence. KEYWORDS Kaposi's sarcoma-associated herpesvirus, LANA speckles, cytoplasmic DNA sensors, cytoplasmic variants, structure, virus persistence K aposi's sarcoma herpesvirus (KSHV) is the cause of three human malignanciesKaposi's sarcoma (KS), primary effusion lymphoma (PEL), and the plasma cell variant of multicentric Castleman's disease (MCD). Like other herpesviruses, it establishes a lifelong infection of the host. KSHV persistence involves latency, during which no viral particles are produced, only a limited set of viral genes is expressed, and the circular latent genome is replicated and segregated to daughter cells as an episome by the host replication and cell division machinery. However, this mechanism of persistence is probably not very efficient as illustrated by the fact that, in cell culture, most KSHV-infected cells lose the viral genome rapidly (1). Notable exceptions to this rule are cultured cell lines established from PEL samples, which retain the viral genome indefinitely (2, 3). It is therefore possible that occasional low-level virus production and infection of new cells may be required for the persistence of KSHV in the infected host (1). LANA DISCOVERY AND CHARACTERIZATIONOne of the few proteins expressed during the latent phase of the viral life cycle, as well as in all KSHV-infected tumor cells, is the latency-associated nuclear antigen (LANA), which is essential for viral persistence. In this review, we focus on recently identified features of LANA that relate to its role in both the latent and lytic replication cycles during viral persistence. For a more comprehensive overview of LANA and its functions, we refer the reader to several excellent recent reviews (4-7).LANA was initially identified as a "speckled" nuclear fluorescence staining pattern (see Fig. 1A) recognized by serum antibodies from KSHV-infected patients (8-11). The size of the LANA protein is heterogeneous, and multiple protein bands in the range of 150 to 230 kDa, thought to be mostly the result of posttranslational modifications, can be seen on Western blots of lysates of infected cells (12)(13)(14)(15)(16)(17). LANA is encoded by KSHV ORF73, and ORF73 and the neighboring genes ORF72/vcyc (viral cyclin), ORF71/vFLIP (viral FLICE inhibitory protein), and K12/kaposin and a transcript encoding 12 micro-

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“…For example, the product of ORF-K15 is a polytopic transmembrane protein whose cytosolic tail can under-go tyrosine phosphorylation, leading to TRAF3 recruitment and NF-κB activation. The net result is activation of a large program of cytokine and chemokine expression (179,180).…”

Section: How Does Kshv Infection Predispose To Ks?mentioning

confidence: 99%

KSHV and the pathogenesis of Kaposi sarcoma: listening to human biology and medicine

Ganem¹

2010

J. Clin. Invest.

341

380

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A Systems Biology Approach To Identify the Combination Effects of Human Herpesvirus 8 Genes on NF-κB Activation

Abstract: Human herpesvirus 8 (HHV-8

Cited by 48 publications

References 72 publications

Activation of NF-κB by the Kaposi's Sarcoma-Associated Herpesvirus K15 Protein Involves Recruitment of the NF-κB-Inducing Kinase, IκB Kinases, and Phosphorylation of p65

Activation of NF-κB by the Kaposi's Sarcoma-Associated Herpesvirus K15 Protein Involves Recruitment of the NF-κB-Inducing Kinase, IκB Kinases, and Phosphorylation of p65

Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen: Replicating and Shielding Viral DNA during Viral Persistence

KSHV and the pathogenesis of Kaposi sarcoma: listening to human biology and medicine

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