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

✍ Scribed by Jian Song; Takako Ohkura; Masamichi Sugimoto; Yasuko Mori; Reiko Inagi; Koichi Yamanishi; Kazuyuki Yoshizaki; Norihiro Nishimoto

• Publisher: John Wiley and Sons
• Year: 2002
• Tongue: English
• Weight: 182 KB
• Volume: 68
• Category: Article
• ISSN: 0146-6615
• DOI: 10.1002/jmv.10218

✦ Synopsis

Abstract

Human herpesvirus‐8 (HHV‐8) is etiologically associated with Kaposi's sarcoma (KS), body cavity‐based lymphoma (BCBL), and multicentric Castleman's disease (MCD). These HHV‐8‐associated diseases arise predominantly in acquired immunodeficiency syndrome (AIDS) patients. Human interleukin‐6 (huIL‐6) elevated in the serum of AIDS patients is suggested to stimulate the growth of KS and BCBL and to augment the symptoms of MCD. To determine whether huIL‐6 stimulates HHV‐8 replication directly, expression of the HHV‐8 ORF‐50 immediate‐early gene (transcription activator) and ORF‐26 late lytic gene (a capsid protein) was assessed in a BCBL‐1 cell line stimulated by huIL‐6 by means of real‐time reverse transcription‐polymerase chain reaction. huIL‐6 induced both ORF‐50 and ORF‐26 expression, and the maximal ORF‐50 expression appeared earlier than that of ORF‐26. The data indicate that huIL‐6 reactivates HHV‐8 in BCBL‐1 cells through inducing ORF‐50. We also confirmed the previously reported activities of HHV‐8‐encoded huIL‐6 homologue (viral interleukin‐6 [vIL‐6]) on human immunodeficiency virus (HIV) replication in U1 cell line and huIL‐6 production by MT‐4 T cells, and utilizing monoclonal antibodies to the huIL‐6 receptor components, we elucidated that gp130 is the signaling molecule necessary for these vIL‐6 activities. These data suggest the possible existence of interaction between HIV and HHV‐8 via IL‐6, and that the blockade of IL‐6 signal by anti‐IL‐6R antibody or anti‐gp130 antibody can constitute a strategy to treat HIV/HHV‐8 dually infected patients. J. Med. Virol. 68:404–411, 2002. © 2002 Wiley‐Liss, Inc.