PMID- 18987143
OWN - NLM
STAT- MEDLINE
DCOM- 20090126
LR  - 20181113
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 83
IP  - 2
DP  - 2009 Jan
TI  - Intracellular signaling mechanisms and activities of human herpesvirus 8 
      interleukin-6.
PG  - 722-33
LID - 10.1128/JVI.01517-08 [doi]
AB  - Human herpesvirus 8 (HHV-8)-encoded viral interleukin-6 (vIL-6) has been 
      implicated as a key factor in virus-associated neoplasia because of its 
      proproliferative and survival effects and also in view of its angiogenic 
      properties. A major difference between vIL-6 and human IL-6 (hIL-6) is that 
      vIL-6, uniquely, is largely retained and can signal intracellularly. While vIL-6 
      is generally considered to be a lytic gene, several reports have noted its 
      low-level expression in latently infected primary effusion lymphoma (PEL) 
      cultures, in the absence of other lytic gene expression. Thus, intracellular 
      autocrine signal transduction by the viral cytokine may be of particular 
      relevance to the growth and survival of latently infected cells and to 
      pathogenesis. Here we report that most intracellular vIL-6 is located in the 
      endoplasmic reticulum (ER), signals via the gp130 signal transducer in this 
      compartment, and does so independently of the gp80 alpha-subunit of the IL-6 
      receptor, required for hIL-6 signal transduction. Signaling and biological assays 
      incorporating ER-retained vIL-6 and hIL-6 confirmed vIL-6 activity, specifically, 
      in this compartment. Knockdown of vIL-6 expression in PEL cells led to markedly 
      reduced cell growth in normal culture, independently of extracellular cytokines. 
      This could be reversed by reintroduction via virus vector of exclusively 
      ER-retained vIL-6. These data indicate that in virus biology vIL-6 may act to 
      support the growth and survival of cells latently infected with HHV-8 in an 
      autocrine manner via intracrine signaling and that these activities may 
      contribute to the maintenance of latently infected cells and to virus-induced 
      neoplasia.
FAU - Chen, Daming
AU  - Chen D
AD  - Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins 
      University School of Medicine, Baltimore, Maryland 21287, USA.
FAU - Sandford, Gordon
AU  - Sandford G
FAU - Nicholas, John
AU  - Nicholas J
LA  - eng
GR  - R01 CA076445/CA/NCI NIH HHS/United States
GR  - R01-CA76445/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20081105
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (IL6R protein, human)
RN  - 0 (Interleukin-6)
RN  - 0 (Receptors, Interleukin-6)
RN  - 0 (Viral Proteins)
RN  - 0 (interleukin-6, RRV-HHV-8)
RN  - 133483-10-0 (Cytokine Receptor gp130)
SB  - IM
MH  - Cell Line
MH  - Cytokine Receptor gp130/metabolism
MH  - Endoplasmic Reticulum/chemistry
MH  - Gene Knockdown Techniques
MH  - Herpesvirus 8, Human/*physiology
MH  - Humans
MH  - Interleukin-6/*metabolism
MH  - Receptors, Interleukin-6/metabolism
MH  - *Signal Transduction
MH  - Viral Proteins/*metabolism
PMC - PMC2612405
EDAT- 2008/11/07 09:00
MHDA- 2009/01/27 09:00
PMCR- 2009/07/01
CRDT- 2008/11/07 09:00
PHST- 2008/11/07 09:00 [pubmed]
PHST- 2009/01/27 09:00 [medline]
PHST- 2008/11/07 09:00 [entrez]
PHST- 2009/07/01 00:00 [pmc-release]
AID - JVI.01517-08 [pii]
AID - 1517-08 [pii]
AID - 10.1128/JVI.01517-08 [doi]
PST - ppublish
SO  - J Virol. 2009 Jan;83(2):722-33. doi: 10.1128/JVI.01517-08. Epub 2008 Nov 5.