A New Primary Effusion Lymphoma-Derived Cell Line Yields a Highly Infectious Kaposi's Sarcoma Herpesvirus-Containing Supernatant

Cannon, Jennifer S.; Ciufo, Dolores M.; Hawkins, Anita L.; Griffin, Constance A.; Borowitz, Michael J.; Hayward, Gary S.; Ambinder, Richard F.

doi:10.1128/jvi.74.21.10187-10193.2000

Cited by 148 publications

(122 citation statements)

References 36 publications

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“…22 Furthermore, expression of the CD20 antigen has been recently demonstrated in 1 patient with acquired immunodeficiency syndrome (AIDS)-associated primary effusion lymphoma in vivo and in vitro. 23 Long-term ablation of KSHV viremia should thus be viewed a therapeutic goal to prevent the periodic exacerbations of MCD and the subsequent development of lymphoma.…”

Section: Resultsmentioning

confidence: 99%

Long-term remission of Kaposi sarcoma–associated herpesvirus-related multicentric Castleman disease with anti-CD20 monoclonal antibody therapy

Corbellino

Bestetti

Scalamogna

et al. 2001

Blood

128

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Section: Resultsmentioning

confidence: 99%

Long-term remission of Kaposi sarcoma–associated herpesvirus-related multicentric Castleman disease with anti-CD20 monoclonal antibody therapy

Corbellino

Bestetti

Scalamogna

et al. 2001

Blood

128

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“…As we and others have demonstrated, BCBL-1 cells are only partly dependent upon the presence of vIL-6. Moreover, vIL-6 expression was detected in less than 2% of the cells (10). Due to the low transfection efficacy of BCBL-1 cells and the small number of BCBL cells that express vIL-6, we first chose to demonstrate the universal application of MAV as a vIL-6 neutralizing intrabody in COS-7 cells.…”

Section: Discussionmentioning

confidence: 99%

Abrogation of Viral Interleukin-6 (vIL-6)-Induced Signaling by Intracellular Retention and Neutralization of vIL-6 with an Anti-vIL-6 Single-Chain Antibody Selected by Phage Display

Kovaleva

Bußmeyer

Rabe

et al. 2006

J Virol

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Human herpesvirus 8 (HHV-8) encodes several putative oncogenes, which are homologues to cellular host genes known to function in cell cycle regulation, control of apoptosis, and cytokine signaling. Viral interleukin (vIL-6) is believed to play an important role in the pathogenesis of Kaposi's sarcoma as well as primary effusion lymphoma and multicentric Castleman's disease. Therefore, vIL-6 is a promising target for novel therapies directed against HHV-8-associated diseases. By phage display screening of human synthetic antibody libraries, we have selected a specific recombinant antibody, called monoclonal anti-vIL-6 (MAV), binding to vIL-6. The epitope recognized by MAV was localized on the top of the D helix of the vIL-6 protein, which is a part of receptor binding site III. Consequently, MAV specifically inhibits vIL-6-mediated growth of the primary effusion lymphoma-derived cell line BCBL-1 and blocks STAT3 phosphorylation in the human hepatoma cell line HepG2. Since it was previously found that vIL-6 can also induce signals from within the cell, presumably within the endoplasmic reticulum, we fused the recombinant antibody MAV with the endoplasmic retention sequence KDEL (MAV-KDEL). As a result, COS-7 cells expressing MAV-KDEL and synthesizing vIL-6 ceased to secrete the cytokine. Moreover, we observed that vIL-6 that was bound to MAV-KDEL and retained in the endoplasmic reticulum did not induce STAT3 phosphorylation in HepG2 cells. We conclude that the activity of the intracellularly retained vIL-6 protein is neutralized by MAV-KDEL. Our results might represent a novel therapeutic strategy to neutralize virally encoded growth factors or oncogenes.

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“…Plasmid Construction-To express the KSHV ORF57-GFP fusion protein in mammalian cells, a KSHV ORF57 cDNA from nt 82069 to 83541 in the KSHV genome was amplified by RT-PCR from JSC-1 cells, a KSHV ϩ and EBV ϩ B cell line (35), using a 5Ј primer (oVM68, 5Ј-TACTCAGAATTCACC/ATGGTA-CAAGCAATGATAGACATGG-3Ј) in combination with a 3Ј primer (oVM70, 5Ј-ATCGTGGATCC/GAAAGTGGATA-AAAGAATAAACCCTTG-3Ј). The cDNA without an intron was cloned in-frame at the GFP N terminus in the mammalian expression vector pEGFP-N1 (Clontech) via its EcoRI and BamHI sites.…”

Section: Methodsmentioning

confidence: 99%

Structural and Functional Analyses of Kaposi Sarcoma-associated Herpesvirus ORF57 Nuclear Localization Signals in Living Cells

Majerčiak

Yamanegi

Nie

et al. 2006

Journal of Biological Chemistry

206

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Kaposi sarcoma-associated herpesvirus (KSHV) ORF57 is a multifunctional, nuclear protein involved in post-transcriptional regulation of a subset of viral genes during lytic replication. Three nuclear localization signals (NLSs), NLS1 (amino acids (aa 101-107), NLS2 (aa 121-130), and NLS3 (aa 143-152), were identified in the N terminus of the ORF57 protein, and each of the three represents a short stretch of basic amino acid residues. Disruption of all three NLSs prevented localization of ORF57 in the nucleus. Insertion of individual NLSs into a heterologous cytoplasmic protein converted it into a nuclear protein, confirming that each NLS functions independently and is sufficient to promote protein nuclear localization. Although it exhibits a function similar to that of Epstein-Barr virus EB2 in promoting KSHV ORF59 expression, KSHV ORF57 differs from the herpes simplex virus ICP27 protein, and its function could be disrupted by point mutations of single or two NLSs in random combination, despite the proper localization of the mutant protein in the nucleus. The dysfunctional ORF57 containing NLS mutations also had low affinity with ORF59 RNA and the RNA export factor REF. However, the REF binding of ORF57 in vivo appeared to have no effect on ORF57-mediated enhancement of ORF59 expression. Thus, the three NLSs identified in ORF57 provide at least two functions, nuclear localization of ORF57 and up-regulation of ORF59 expression.

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A New Primary Effusion Lymphoma-Derived Cell Line Yields a Highly Infectious Kaposi's Sarcoma Herpesvirus-Containing Supernatant

Cited by 148 publications

References 36 publications

Long-term remission of Kaposi sarcoma–associated herpesvirus-related multicentric Castleman disease with anti-CD20 monoclonal antibody therapy

Long-term remission of Kaposi sarcoma–associated herpesvirus-related multicentric Castleman disease with anti-CD20 monoclonal antibody therapy

Abrogation of Viral Interleukin-6 (vIL-6)-Induced Signaling by Intracellular Retention and Neutralization of vIL-6 with an Anti-vIL-6 Single-Chain Antibody Selected by Phage Display

Structural and Functional Analyses of Kaposi Sarcoma-associated Herpesvirus ORF57 Nuclear Localization Signals in Living Cells

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