scholarly journals Establishment and Maintenance of Kaposi's Sarcoma-Associated Herpesvirus Latency in B Cells

2005 ◽  
Vol 79 (22) ◽  
pp. 14383-14391 ◽  
Author(s):  
Lei Chen ◽  
Michael Lagunoff
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Lines ◽  
Kaposi's Sarcoma ◽  
Primary Effusion Lymphoma ◽  
Kaposi’S Sarcoma ◽  
Lymphoma Cell ◽  
Kshv Infection ◽  
Primary Effusion Lymphoma Cell ◽  
Cells In Culture

ABSTRACT Kaposi's sarcoma (KS)-associated herpesvirus (KSHV) is the infectious cause of Kaposi's sarcoma and is also associated with two B-cell lymphoproliferative diseases, primary effusion lymphoma and the plasmablastic form of multicentric Castleman's disease. KSHV is also found in the B-cell fraction of peripheral blood mononucleocytes of some KS patients. Despite in vivo infection of B cells and the ability of KSHV to infect many cell types in culture, to date B cells in culture have been resistant to KSHV infection. However, as shown here, the lack of infection is not due to the inability of B cells to support latent KSHV infection. When KSHV DNA is introduced into B cells, the virus is maintained as an episome and can establish and maintain latency over the course of months. As in all primary effusion lymphoma cell lines, there is a low level of spontaneous lytic replication in latently infected BJAB cells. Importantly, viral gene expression is similar to that of primary effusion lymphoma cell lines. Furthermore, the virus can be reactivated to higher levels with specific stimuli and transmitted to other cells, indicating that this is a productive infection. Thus B cells in culture are capable of establishing, maintaining, and reactivating from latency. These studies provide a controlled system to analyze how KSHV alters B cells during KSHV latency and reactivation.

scholarly journals Disruption of the B-cell specific transcriptional program in HHV-8 associated primary effusion lymphoma cell lines

Oncogene ◽  
2003 ◽  
Vol 22 (7) ◽  
pp. 964-973 ◽  
Author(s):  
Meztli Arguello ◽  
Marco Sgarbanti ◽  
Eduardo Hernandez ◽  
Yael Mamane ◽  
Sonia Sharma ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lines ◽  
Primary Effusion Lymphoma ◽  
Lymphoma Cell ◽  
Transcriptional Program ◽  
Primary Effusion Lymphoma Cell

Patterned CpG Methylation of Silenced B Cell Gene Promoters in Classical Hodgkin Lymphoma-derived and Primary Effusion Lymphoma Cell Lines

2005 ◽  
Vol 350 (4) ◽  
pp. 631-640 ◽  
Author(s):  
Jeanette R. Doerr ◽  
Cindy S. Malone ◽  
Francesca M. Fike ◽  
Melinda S. Gordon ◽  
Shahe V. Soghomonian ◽  
...  
Keyword(s):  
B Cell ◽  
Hodgkin Lymphoma ◽  
Cell Lines ◽  
Primary Effusion Lymphoma ◽  
Cpg Methylation ◽  
Lymphoma Cell ◽  
Gene Promoters ◽  
Classical Hodgkin Lymphoma ◽  
Primary Effusion Lymphoma Cell ◽  
Cell Gene

scholarly journals Characterization of Kaposi's Sarcoma-Associated Herpesvirus-Related Lymphomas by DNA Microarray Analysis

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Keiji Ueda ◽  
Eriko Ohsaki ◽  
Kazushi Nakano ◽  
Xin Zheng
Keyword(s):  
Gene Expression ◽  
Cell Lines ◽  
Kaposi's Sarcoma ◽  
Primary Effusion Lymphoma ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Kaposi’S Sarcoma ◽  
Lymphoma Cell ◽  
Kaposi's Sarcoma Associated Herpesvirus ◽  
Kaposi’S Sarcoma Associated Herpesvirus

Among herpesviruses, γ-herpesviruses are supposed to have typical oncogenic activities. Two human γ-herpesviruses, Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV), are putative etiologic agents for Burkitt lymphoma, nasopharyngeal carcinoma, and some cases of gastric cancers, and Kaposi's sarcoma, multicentric Castleman's disease, and primary effusion lymphoma (PEL) especially in AIDS setting for the latter case, respectively. Since such two viruses mentioned above are highly species specific, it has been quite difficult to prove their oncogenic activities in animal models. Nevertheless, the viral oncogenesis is epidemiologically and/or in vitro experimentally evident. This time, we investigated gene expression profiles of KSHV-oriented lymphoma cell lines, EBV-oriented lymphoma cell lines, and T-cell leukemia cell lines. Both KSHV and EBV cause a B-cell-originated lymphoma, but the gene expression profiles were typically classified. Furthermore, KSHV could govern gene expression profiles, although PELs are usually coinfected with KSHV and EBV.

scholarly journals Kaposi's Sarcoma-Associated Herpesvirus Latency Locus Renders B Cells Hyperresponsive to Secondary Infections

2018 ◽  
Vol 92 (19) ◽  
Author(s):  
Sang-Hoon Sin ◽  
Anthony B. Eason ◽  
Rachele Bigi ◽  
Yongbaek Kim ◽  
SunAh Kang ◽  
...  
Keyword(s):  
B Cells ◽  
Transgenic Mice ◽  
B Cell ◽  
Kaposi's Sarcoma ◽  
Primary Effusion Lymphoma ◽  
Castleman’S Disease ◽  
Kaposi’S Sarcoma ◽  
Cell Hyperplasia ◽  
Kaposi's Sarcoma Associated Herpesvirus ◽  
Kaposi’S Sarcoma Associated Herpesvirus

ABSTRACTKaposi's sarcoma-associated herpesvirus (KSHV) induces B cell hyperplasia and neoplasia, such as multicentric Castleman's disease (MCD) and primary effusion lymphoma (PEL). To explore KSHV-induced B cell reprogrammingin vivo, we expressed the KSHV latency locus, inclusive of all viral microRNAs (miRNAs), in B cells of transgenic mice in the absence of the inhibitory FcγRIIB receptor. The BALB/c strain was chosen as this is the preferred model to study B cell differentiation. The mice developed hyperglobulinemia, plasmacytosis, and B lymphoid hyperplasia. This phenotype was ameliorated by everolimus, which is a rapamycin derivative used for the treatment of mantle cell lymphoma. KSHV latency mice exhibited hyperresponsiveness to the T-dependent (TD) antigen mimic anti-CD40 and increased incidence of pristane-induced inflammation. Lastly, the adaptive immunity against a secondary infection with Zika virus (ZIKV) was markedly enhanced. These phenotypes are consistent with KSHV lowering the activation threshold of latently infected B cells, which may be beneficial in areas of endemicity, where KSHV is acquired in childhood and infections are common.IMPORTANCEKaposi's sarcoma-associated herpesvirus (KSHV) establishes latency in B cells and is stringently linked to primary effusion lymphoma (PEL) and the premalignant B cell hyperplasia multicentric Castleman's disease (MCD). To investigate potential genetic background effects, we expressed the KSHV miRNAs in BALB/c transgenic mice. BALB/c mice are the preferred strain for B cell hybridoma development because of their propensity to develop predictable B cell responses to antigen. The BALB/c latency mice exhibited a higher incidence of B cell hyperplasia as well as sustained hyperglobulinemia. The development of neutralizing antibodies against ZIKV was augmented in BALB/c latency mice. Hyperglobulinemia was dampened by everolimus, a derivative of rapamycin, suggesting a role for mTOR inhibitors in managing immune activation, which is hallmark of KSHV infection as well as HIV infection.

scholarly journals Human Immunodeficiency Virus Replication in a Primary Effusion Lymphoma Cell Line Stimulates Lytic-Phase Replication of Kaposi’s Sarcoma-Associated Herpesvirus

1999 ◽  
Vol 73 (12) ◽  
pp. 10329-10338 ◽  
Author(s):  
Vasundhara Varthakavi ◽  
Philip J. Browning ◽  
Paul Spearman
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cell Line ◽  
Kaposi's Sarcoma ◽  
Primary Effusion Lymphoma ◽  
Kaposi’S Sarcoma ◽  
Lytic Replication ◽  
Lymphoma Cell ◽  
Lymphoma Cell Line ◽  
Primary Effusion Lymphoma Cell ◽  
Immunodeficiency Virus

ABSTRACT Human immunodeficiency virus (HIV) and Kaposi’s sarcoma-associated herpesvirus (KSHV) coinfect many individuals in North America and in parts of Africa. Infection with HIV is a leading risk factor for the development of Kaposi’s sarcoma (KS). In this study, we tested the hypothesis that HIV infection of common or adjacent cells would stimulate replication and spread of KSHV. Infection of a primary effusion lymphoma cell line by vesicular stomatitis virus type G-pseudotyped HIV type 1 led to a rapid induction of lytic-phase KSHV replication. Induction of lytic KSHV replication by HIV required active replication of HIV. The addition of the nucleoside reverse transcriptase inhibitor azidothymidine or the protease inhibitor indinavir to the culture prevented HIV spread and inhibited the associated induction of KSHV lytic replication. Lytic replication occurred in both HIV-infected and HIV-uninfected cells within the culture, and could be induced in uninfected cells via a soluble factor released from the HIV-infected cells. Transmission of infectious KSHV to an uninfected target cell was enhanced by HIV replication and was inhibited by antiretroviral drugs. These results may have implications for the pathogenesis and treatment of KS in individuals coinfected with KSHV and HIV.

scholarly journals EphA7 functions as a receptor for cell-to-cell transmission of Kaposi’s sarcoma-associated herpesvirus into BJAB B cells and for cell-free virus infection by the related rhesus monkey rhadinovirus

2019 ◽  
Author(s):  
Anna K. Großkopf ◽  
Sarah Schlagowski ◽  
Bojan F. Hörnich ◽  
Thomas Fricke ◽  
Ronald C. Desrosiers ◽  
...  
Keyword(s):  
B Cells ◽  
Rhesus Monkey ◽  
B Cell ◽  
Cell Line ◽  
Kaposi's Sarcoma ◽  
Primary Effusion Lymphoma ◽  
Kaposi’S Sarcoma ◽  
Target Cells ◽  
Cell Infection ◽  
Cell Transmission

ABSTRACTKaposi’s sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi’s sarcoma and is associated with two B cell malignancies, primary effusion lymphoma and the plasmablastic variant of multicentric Castleman’s disease. EphA2 functions as a cellular receptor for the gH/gL glycoprotein complex of KSHV for several adherent cell types. KSHV gH/gL was previously shown to also weakly interact with other members of the Eph family of receptors. Whether these interactions are of functional consequence remained unclear so far, even if other A-type Ephs were shown to be able to compensate for absence of EphA2 in overexpression systems. Here, we demonstrate for the first time that endogenously expressed EphA7 in BJAB B cells is critical for the cell-to-cell transmission of KSHV from producer iSLK cells to BJAB target cells. The BJAB lymphoblastoid cell line often serves as a model for B cell infection and expresses only low levels of all Eph family receptors other than EphA7. Endogenous EphA7 could be precipitated from the cellular lysate of BJAB cells using recombinant gH/gL, and knockout of EphA7 significantly reduced transmission of KSHV into BJAB target cells by over 80%. Finally, we demonstrate that receptor function of EphA7 is conserved between cell-to-cell transmission of KSHV and cell-free infection by the related rhesus monkey rhadinovirus (RRV), which is relatively even more dependent on EphA7 for infection of BJAB cells.IMPORTANCEInfection of B cells is biologically relevant for two KSHV-associated malignancies, the plasmablastic variant of multicentric Castleman’s disease (MCD) and primary effusion lymphoma (PEL). Elucidating the process of B cell infection is therefore important to understand the pathogenesis of these diseases. For various types of adherent cells, EphA2 has been shown by several groups to function as an entry receptor that is engaged by the gH/gL glycoprotein complex. Our previous findings indicate that KSHV does not only interact with EphA2, but can also bind to other members of the Eph family of receptor tyrosine kinases with comparatively lower avidity. We now analyzed the requirement of Eph interactions for infection of the BJAB B cell line, a model for infection of B cells by KSHV. We identify EphA7 as the principal Eph receptor for infection of this model B cell line by both KSHV and the related rhesus monkey rhadinovirus.

scholarly journals Lytic Replication-Defective Kaposi's Sarcoma-Associated Herpesvirus: Potential Role in Infection and Malignant Transformation

2004 ◽  
Vol 78 (20) ◽  
pp. 11108-11120 ◽  
Author(s):  
Jian-Hong Deng ◽  
Yan-Jin Zhang ◽  
Xin-Ping Wang ◽  
Shou-Jiang Gao
Keyword(s):  
Malignant Transformation ◽  
Cell Lines ◽  
Kaposi's Sarcoma ◽  
Potential Role ◽  
Primary Effusion Lymphoma ◽  
Kaposi’S Sarcoma ◽  
Lytic Replication ◽  
Screening Methods ◽  
Kaposi's Sarcoma Associated Herpesvirus ◽  
Kaposi’S Sarcoma Associated Herpesvirus

ABSTRACT Defective viruses often have pivotal roles in virus-induced diseases. Although Kaposi's sarcoma-associated herpesvirus (KSHV) is etiologically associated with Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL), defective KSHV has not been reported. Using differential genetic screening methods, we show that defective KSHV is present in KS tumors and PEL cell lines. To investigate the role of defective viruses in KSHV-induced pathogenesis, we isolated and characterized a lytic replication-defective KSHV, KV-1, containing an 82-kb genomic deletion of solely lytic genes. Cells harboring KV-1 escaped G0/G1 apoptosis induced by spontaneous lytic replication occurred in cells infected with regular KSHV but maintained efficient latent replication. Consequently, KV-1-infected cells had phenotypes of enhanced cell proliferation and transformation potentials. Importantly, KV-1 was packaged as infectious virions by using regular KSHV as helpers, and KV-1-like variants were detected in cultures of two of five KSHV cell lines and 1 of 18 KS tumors. These results point to a potential role for defective viruses in the regulation of KSHV infection and malignant transformation.

scholarly journals Mechanism of Angiopoietin-1 Upregulation in Kaposi's Sarcoma-Associated Herpesvirus-Infected PEL Cell Lines

2015 ◽  
Vol 89 (9) ◽  
pp. 4786-4797 ◽  
Author(s):  
Xin Zheng ◽  
Eriko Ohsaki ◽  
Keiji Ueda
Keyword(s):  
Cell Lines ◽  
Kaposi's Sarcoma ◽  
Primary Effusion Lymphoma ◽  
Regulatory Region ◽  
Leukemia Cell ◽  
Kaposi’S Sarcoma ◽  
Dependent Manner ◽  
Kaposi's Sarcoma Associated Herpesvirus ◽  
Kaposi’S Sarcoma Associated Herpesvirus ◽  
Angiopoietin 1

ABSTRACTAngiopoietin-1 (ANGPT-1) is a secreted glycoprotein that was first characterized as a ligand of the Tie2 receptor. In a previous study using microarray analysis, we found that the expression of ANGPT-1 was upregulated in Kaposi's sarcoma-associated herpesvirus (KSHV)-infected primary effusion lymphoma (PEL) cell lines compared with that in uninfected Burkitt and other leukemia cell lines. Other authors have also reported focal expression of ANGPT-1 mRNA in biopsy specimens of Kaposi's sarcoma (KS) tissue from patients with AIDS. Here, to confirm these findings, we examined the expression and secretion levels of ANGPT-1 in KSHV-infected PEL cell lines and address the mechanisms ofANGPT-1transcriptional regulation. We also showed that ANGPT-1 was expressed and localized in the cytoplasm and secreted into the supernatant of KSHV-infected PEL cells. Deletion studies of the regulatory region revealed that the region encompassing nucleotides −143 to −125 of theANGPT-1-regulating sequence was responsible for this upregulation. Moreover, an electrophoretic mobility shift assay and chromatin immunoprecipitation, followed by quantitative PCR, suggested that some KSHV-infected PEL cell line-specific DNA-binding factors, such as OCT-1, should be involved in the upregulation ofANGPT-1in a sequence-dependent manner.IMPORTANCEWe confirmed that ANGPT-1 was expressed in and secreted from KSHV-infected PEL cells and that the transcriptional activity ofANGPT-1was upregulated. A 19-bp fragment was identified as the region responsible forANGPT-1upregulation through binding with OCT-1 as a core factor in PEL cells. This study suggests that ANGPT-1 is overproduced in KSHV-infected PEL cells, which could affect the pathophysiology of AIDS patients with PEL.

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