Human interleukin-6 induces human herpesvirus-8 replication in a body cavity-based lymphoma cell line

2002 ◽  
Vol 68 (3) ◽  
pp. 404-411 ◽  
Author(s):  
Jian Song ◽  
Takako Ohkura ◽  
Masamichi Sugimoto ◽  
Yasuko Mori ◽  
Reiko Inagi ◽  
...  
Keyword(s):  
Cell Line ◽  
Interleukin 6 ◽  
Human Herpesvirus ◽  
Body Cavity ◽  
Lymphoma Cell ◽  
Human Herpesvirus 8 ◽  
Lymphoma Cell Line ◽  
Herpesvirus 8

scholarly journals Human Herpesvirus 8 Gene Encodes a Functional Thymidylate Synthase

2002 ◽  
Vol 76 (20) ◽  
pp. 10530-10532 ◽  
Author(s):  
Gábor Gáspár ◽  
Erik De Clercq ◽  
Johan Neyts
Keyword(s):  
Cell Line ◽  
Thymidylate Synthase ◽  
Kaposi's Sarcoma ◽  
Human Herpesvirus ◽  
Kaposi’S Sarcoma ◽  
Lymphoma Cell ◽  
Human Herpesvirus 8 ◽  
Lymphoma Cell Line ◽  
Herpesvirus 8

ABSTRACT We demonstrate that human herpesvirus 8, obtained from the lymphoma cell line BC-3 as well as from Kaposi's sarcoma lesions, carries a gene that encodes a functional thymidylate synthase (TS). The particular characteristics of this enzyme are studied and compared to the characteristics of TSs encoded by other organisms.

Human herpesvirus 8-encoded interleukin 6 activates HIV-1 in the U1 monocytic cell line

AIDS ◽  
1999 ◽  
Vol 13 (14) ◽  
pp. 1851-1855 ◽  
Author(s):  
Julia R. Gage ◽  
Elizabeth Crabb Breen ◽  
Angela Echeverri ◽  
Larry Magpantay ◽  
Tadamitsu Kishimoto ◽  
...  
Keyword(s):  
Cell Line ◽  
Interleukin 6 ◽  
Human Herpesvirus ◽  
Human Herpesvirus 8 ◽  
Monocytic Cell ◽  
Monocytic Cell Line ◽  
Herpesvirus 8 ◽  
Hiv 1

scholarly journals Human Herpesvirus 8 Interleukin-6 (vIL-6) Signals through gp130 but Has Structural and Receptor-Binding Properties Distinct from Those of Human IL-6

1999 ◽  
Vol 73 (10) ◽  
pp. 8268-8278 ◽  
Author(s):  
Xiaoyu Wan ◽  
Hailin Wang ◽  
John Nicholas
Keyword(s):  
Signal Transduction ◽  
Transcription Factors ◽  
Receptor Binding ◽  
Interleukin 6 ◽  
Human Herpesvirus ◽  
Body Cavity ◽  
Human Herpesvirus 8 ◽  
Binding Properties ◽  
Herpesvirus 8 ◽  
Functional Studies

ABSTRACT Human herpesvirus 8 (HHV-8) has been associated with classical, endemic (African), and AIDS-related Kaposi’s sarcoma (KS), body cavity-based primary effusion lymphomas, and multicentric Castleman’s disease (MCD). HHV-8 encodes a functional homologue of interleukin-6 (IL-6), a cytokine that promotes the growth of KS and myeloma cells and is found at elevated levels in MCD lesions and patient sera. We have previously reported that the viral IL-6 (vIL-6) gene product can support the growth of the IL-6-dependent murine hybridoma cell line, B9, and that the gp80 (IL-6 receptor [IL-6R]) component of the IL-6 receptor-signal transducer (gp180) complex plays a role in mediating this activity. However, it has been shown by others that vIL-6 can function in human cells independently of IL-6R. Here we have extended our functional studies of vIL-6 by identifying transcription factors and pathways used in human Hep3B cells, investigating the utilization of gp130 and IL-6R by vIL-6, and undertaking mutational analyses of vIL-6 and gp130. The data presented here establish that vIL-6, in common with its endogenous counterparts, can mediate signal transduction through gp130 and activate multiple transcription factors, map residues within the vIL-6 protein that are and are not important for vIL-6 signalling, and identify a gp130 mutant that is nonfunctional with respect to vIL-6 signalling in the absence of IL-6R but that retains the ability to mediate vIL-6 and human IL-6 (hIL-6) signal transduction when IL-6R is coexpressed. The data presented demonstrate functional and mechanistic similarities between vIL-6 and endogenous IL-6 proteins but also highlight differences in the structural and receptor-binding properties of vIL-6 relative to its human counterpart.

Association of Primary Pleural Effusion Lymphoma of T-Cell Origin and Human Herpesvirus 8 in a Human Immunodeficiency Virus–Seronegative Man

2001 ◽  
Vol 125 (9) ◽  
pp. 1246-1248 ◽  
Author(s):  
Emmanuèle Lechapt-Zalcman ◽  
Dominique Challine ◽  
Marie-Hélène Delfau-Larue ◽  
Corinne Haioun ◽  
Dominique Desvaux ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Dna Sequences ◽  
Primary Effusion Lymphoma ◽  
Polymerase Chain Reaction Amplification ◽  
Human Herpesvirus ◽  
Body Cavity ◽  
Human Herpesvirus 8 ◽  
Herpesvirus 8 ◽  
Immunodeficiency Virus

Abstract We describe a case of an 87-year-old human immunodeficiency virus (HIV)–negative man who developed a primary pleural lymphoma without any identifiable tumor mass associated with human herpesvirus 8 (HHV-8) infection. A large T-cell lymphoma was diagnosed based on morphologic, immunophenotypic, and molecular findings. The HHV-8 DNA sequences were detected using specific polymerase chain reaction amplification in the lymphomatous effusion. Study of the patient's serum confirmed the HHV-8 infection. This case report displays the characteristic features of HHV-8–related body cavity-based lymphoma/primary effusion lymphoma previously reported in HIV-seronegative patients, except that it is of T-cell origin. Whether this case may be included or not within the primary effusion lymphoma entity, the association of a pleural T-cell non-Hodgkin lymphoma with HHV-8 infection raises the question of the possible occurrence of T cells as the target of malignant transformation associated with HHV-8 infection.

Human herpesvirus 8-encoded interleukin-6 homologue (viral IL-6) induces endogenous human IL-6 secretion

2000 ◽  
Vol 61 (3) ◽  
pp. 332-335 ◽  
Author(s):  
Yasuko Mori ◽  
Norihiro Nishimoto ◽  
Mika Ohno ◽  
Reiko Inagi ◽  
Panadda Dhepakson ◽  
...  
Keyword(s):  
Interleukin 6 ◽  
Human Herpesvirus ◽  
Human Herpesvirus 8 ◽  
Herpesvirus 8

scholarly journals Genetic Analyses of Contributions of Viral Interleukin-6 Interactions and Signaling to Human Herpesvirus 8 Productive Replication

2020 ◽  
Vol 94 (19) ◽  
Author(s):  
Qian Li ◽  
Qiwang Xiang ◽  
Daming Chen ◽  
John Nicholas
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Interactions ◽  
Interleukin 6 ◽  
Kaposi's Sarcoma ◽  
Castleman’S Disease ◽  
Human Herpesvirus ◽  
Human Herpesvirus 8 ◽  
Signal Transducer ◽  
Herpesvirus 8 ◽  
Productive Replication

ABSTRACT Human herpesvirus 8 (HHV-8) viral interleukin-6 (vIL-6) is a cytokine that is poorly secreted and localized largely to the endoplasmic reticulum (ER). It has been implicated, along with other HHV-8 proinflammatory and/or angiogenic viral proteins, in HHV-8-associated Kaposi’s sarcoma, primary effusion lymphoma (PEL), and multicentric Castleman’s disease (MCD), in addition to an MCD-related disorder involving systemic elevation of proinflammatory cytokines, including vIL-6 and human IL-6 (hIL-6). In these diseases, lytic (productive) replication, in addition to viral latency, is believed to play a critical role. Proreplication activity of vIL-6 has been identified experimentally in PEL and endothelial cells, but the relative contributions of different vIL-6 interactions have not been established. Productive interactions of vIL-6 with the IL-6 signal transducer, gp130, can occur within the ER, but vIL-6 also interacts in the ER with a nonsignaling receptor called vitamin K epoxide reductase complex subunit 1 variant 2 (VKORC1v2), calnexin, and VKORC1v2- and calnexin-associated proteins UDP-glucose:glycoprotein glucosyltransferase 1 (UGGT1) and glucosidase II (GlucII). Here, we report the systematic characterization of interaction-altered vIL-6 variants and the lytic phenotypes of recombinant viruses expressing selected variants. Our data identify the critical importance of vIL-6 and its ER-localized activity via gp130 to productive replication in inducible SLK (epithelial) cells, absence of detectable involvement of vIL-6 interactions with VKORC1v2, GlucII, or UGGT1, and the insufficiency and lack of direct contributory effects of extracellular signaling by vIL-6 or hIL-6. These findings, obtained through genetics-based approaches, complement and extend previous analyses of vIL-6 activity. IMPORTANCE Human herpesvirus 8 (HHV-8)-encoded viral interleukin-6 (vIL-6) was the first viral IL-6 homologue to be identified. Experimental and clinical evidence suggests that vIL-6 is important for the onset and/or progression of HHV-8-associated endothelial-cell and B-cell pathologies, including AIDS-associated Kaposi’s sarcoma and multicentric Castleman’s disease. The protein is unusual in its poor secretion from cells and its intracellular activity; it interacts, directly or indirectly, with a number of proteins beyond the IL-6 signal transducer, gp130, and can mediate activities through these interactions in the endoplasmic reticulum. Here, we report the characterization with respect to protein interactions and signal-transducing activity of a panel of vIL-6 variants and utilization of HHV-8 mutant viruses expressing selected variants in phenotypic analyses. Our findings establish the importance of vIL-6 in HHV-8 productive replication and the contributions of individual vIL-6-protein interactions to HHV-8 lytic biology. This work furthers understanding of the biological significance of vIL-6 and its unique intracellular interactions.

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