PMID- 10482577
OWN - NLM
STAT- MEDLINE
DCOM- 19991012
LR  - 20200724
IS  - 0022-538X (Print)
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Linking)
VI  - 73
IP  - 10
DP  - 1999 Oct
TI  - Human herpesvirus 8 interleukin-6 (vIL-6) signals through gp130 but has 
      structural and receptor-binding properties distinct from those of human IL-6.
PG  - 8268-78
AB  - 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.
FAU - Wan, X
AU  - Wan X
AD  - Molecular Virology Laboratories, Department of Oncology, Johns Hopkins University 
      School of Medicine, Baltimore, Maryland 21231, USA.
FAU - Wang, H
AU  - Wang H
FAU - Nicholas, J
AU  - Nicholas J
LA  - eng
GR  - R01 CA076445/CA/NCI NIH HHS/United States
GR  - R01 CA76445/CA/NCI NIH HHS/United States
GR  - R55 CA76445/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Antigens, CD)
RN  - 0 (IL6ST protein, human)
RN  - 0 (Interleukin-6)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Receptors, Interleukin-6)
RN  - 0 (Viral Proteins)
RN  - 133483-10-0 (Cytokine Receptor gp130)
SB  - IM
MH  - Antigens, CD/*metabolism
MH  - Binding Sites
MH  - Cytokine Receptor gp130
MH  - Herpesviridae Infections/*metabolism/physiopathology
MH  - Herpesvirus 8, Human/*metabolism
MH  - Humans
MH  - Interleukin-6/*metabolism
MH  - Membrane Glycoproteins/*metabolism
MH  - Receptors, Interleukin-6/*metabolism
MH  - *Signal Transduction
MH  - Species Specificity
MH  - Viral Proteins/*metabolism
PMC - PMC112844
EDAT- 1999/09/11 00:00
MHDA- 1999/09/11 00:01
PMCR- 1999/10/01
CRDT- 1999/09/11 00:00
PHST- 1999/09/11 00:00 [pubmed]
PHST- 1999/09/11 00:01 [medline]
PHST- 1999/09/11 00:00 [entrez]
PHST- 1999/10/01 00:00 [pmc-release]
AID - 0504 [pii]
AID - 10.1128/JVI.73.10.8268-8278.1999 [doi]
PST - ppublish
SO  - J Virol. 1999 Oct;73(10):8268-78. doi: 10.1128/JVI.73.10.8268-8278.1999.