PMID- 10769064
OWN - NLM
STAT- MEDLINE
DCOM- 20000609
LR  - 20061115
IS  - 0022-1317 (Print)
IS  - 0022-1317 (Linking)
VI  - 81
IP  - Pt 5
DP  - 2000 May
TI  - Ectromelia, vaccinia and cowpox viruses encode secreted interleukin-18-binding 
      proteins.
PG  - 1223-30
AB  - Interleukin-18 (IL-18) is a proinflammatory cytokine that plays a key role in the 
      activation of natural killer and T helper 1 cell responses principally by 
      inducing interferon-gamma (IFN-gamma). Human and mouse secreted IL-18-binding 
      proteins (IL-18BPs) have recently been described which block IL-18 activity but 
      have no sequence similarity to membrane IL-18 receptors. Several poxvirus genes 
      encode proteins with sequence similarity to IL-18BPs. Here we show that vaccinia, 
      ectromelia and cowpox viruses secrete from infected cells a soluble IL-18BP 
      (vIL-18BP) that may modulate the host antiviral response. The ectromelia virus 
      protein was found to block NF-kappaB activation and induction of IFN-gamma in 
      response to IL-18. The highly attenuated vaccinia virus modified virus Ankara 
      encodes IL-18-binding activity, and thus deletion of the vIL-18BP may improve 
      further the safety and immunogenicity of this promising human vaccine candidate. 
      We confirm that molluscum contagiosum virus, a molluscipoxvirus that produces 
      small skin tumours in immunocompetent individuals and opportunistic infections in 
      immunodeficient AIDS patients, also encodes a related, larger vIL-18BP (gene 
      MC54L). This protein may contribute to the lack of inflammatory response 
      characteristic of molluscum contagiosum virus lesions. The expression of 
      vIL-18BPs by distinct poxvirus genera that cause local or general viral 
      dissemination, or persistent or acute infections in the host, emphasizes the 
      importance of IL-18 in response to viral infections.
FAU - Smith, V P
AU  - Smith VP
AD  - Division of Virology, Department of Pathology, University of Cambridge, Tennis 
      Court Road, Cambridge CB2 1QP, UK.
FAU - Bryant, N A
AU  - Bryant NA
FAU - Alcami, A
AU  - Alcami A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Gen Virol
JT  - The Journal of general virology
JID - 0077340
RN  - 0 (Culture Media)
RN  - 0 (Glycoproteins)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 0 (interleukin-18 binding protein)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Baculoviridae/genetics
MH  - Cell Line
MH  - Cowpox virus/genetics/metabolism
MH  - Culture Media
MH  - Ectromelia virus/genetics/metabolism
MH  - Glycoproteins/chemistry/*genetics/*metabolism
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Molecular Sequence Data
MH  - Molluscum contagiosum virus/genetics/metabolism
MH  - Orthopoxvirus/*genetics/*metabolism
MH  - Recombinant Proteins/metabolism
MH  - Spleen/cytology/metabolism
MH  - Vaccinia virus/genetics/metabolism
EDAT- 2000/04/18 09:00
MHDA- 2000/06/17 09:00
CRDT- 2000/04/18 09:00
PHST- 2000/04/18 09:00 [pubmed]
PHST- 2000/06/17 09:00 [medline]
PHST- 2000/04/18 09:00 [entrez]
AID - 10.1099/0022-1317-81-5-1223 [doi]
PST - ppublish
SO  - J Gen Virol. 2000 May;81(Pt 5):1223-30. doi: 10.1099/0022-1317-81-5-1223.