Human interleukin-6 induces human herpesvirus-8 replication in a body cavity-based lymphoma cell line.
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.
Song
Jian
J
Department of Medical Science I, School of Health and Sport Sciences, Osaka University, Osaka, Japan.
Ohkura
Takako
T
Sugimoto
Masamichi
M
Mori
Yasuko
Y
Inagi
Reiko
R
Yamanishi
Koichi
K
Yoshizaki
Kazuyuki
K
Nishimoto
Norihiro
N
D016655:HIV Core Protein p24 / Q000378:metabolism; D019288:Herpesvirus 8, Human / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism; D015850:Interleukin-6 / Q000494:pharmacology / Q000502:physiology*; D008223:Lymphoma; D010940:Plant Proteins; D012367:RNA, Viral / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014764:Viral Proteins / Q000378:metabolism; D014775:Virus Activation; D014779:Virus Replication / Q000187:drug effects*
D016655:HIV Core Protein p24; D017874:Immediate-Early Proteins; D015850:Interleukin-6; C098558:Orf265 protein, Sorghum bicolor; D010940:Plant Proteins; D012367:RNA, Viral; C417604:Rta protein, Human herpesvirus 8; D015534:Trans-Activators; D014764:Viral Proteins