PMID- 12941906
OWN - NLM
STAT- MEDLINE
DCOM- 20031023
LR  - 20190508
IS  - 0022-538X (Print)
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Linking)
VI  - 77
IP  - 18
DP  - 2003 Sep
TI  - Vaccinia virus interleukin-18-binding protein promotes virulence by reducing 
      gamma interferon production and natural killer and T-cell activity.
PG  - 9960-8
AB  - Interleukin-18 (IL-18) is a proinflammatory cytokine that promotes natural killer 
      (NK) and T-cell activation. Several poxviruses, including vaccinia virus (VV), 
      encode a soluble IL-18-binding protein (IL-18bp). The role of the VV IL-18bp 
      (gene C12L) in vivo was studied with wild-type (vC12L), deletion mutant 
      (vDeltaC12L), and revertant (vC12L-rev) viruses in a murine intranasal model of 
      infection. The data show that vDeltaC12L was markedly attenuated, characterized 
      by a mild weight loss and reduced virus titers in lungs, brain, and spleen. Three 
      days after infection, NK cytotoxic activity was augmented in the lung, spleen, 
      and mediastinal lymph nodes (MLNs) of vDeltaC12L-infected mice compared to 
      controls. Seven days after infection, vDeltaC12L-infected mice displayed 
      heightened VV-specific cytotoxic T-lymphocyte (CTL) responses in the lungs, 
      spleen, and MLNs. Gamma interferon (IFN-gamma) levels were also dramatically 
      elevated in lavage fluids and cells from lungs of mice infected with vDeltaC12L. 
      Finally, we demonstrate that IL-18 is produced in vitro and in vivo after VV 
      infection. Taken together, these data demonstrate a role for the vIL-18bp in 
      counteracting IL-18 in both the innate and the specific immune response to VV 
      infection and indicate that the ability of IL-18 to promote vigorous T-cell 
      responses (cytotoxic activity and IFN-gamma production) is a critical factor in 
      the accelerated clearance of the vDeltaC12L mutant.
FAU - Reading, Patrick C
AU  - Reading PC
AD  - Department of Virology, Faculty of Medicine, Imperial College London, St. Mary's 
      Campus, Norfolk Place, London W2 1PG, United Kingdom.
FAU - Smith, Geoffrey L
AU  - Smith GL
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Glycoproteins)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Viral Proteins)
RN  - 0 (interleukin-18 binding protein)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Animals
MH  - Glycoproteins/*physiology
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins
MH  - Interferon-gamma/*biosynthesis
MH  - Killer Cells, Natural/*immunology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - T-Lymphocytes/*immunology
MH  - Vaccinia virus/*pathogenicity
MH  - Viral Proteins/*physiology
MH  - Virulence
PMC - PMC224600
EDAT- 2003/08/28 05:00
MHDA- 2003/10/24 05:00
PMCR- 2003/09/01
CRDT- 2003/08/28 05:00
PHST- 2003/08/28 05:00 [pubmed]
PHST- 2003/10/24 05:00 [medline]
PHST- 2003/08/28 05:00 [entrez]
PHST- 2003/09/01 00:00 [pmc-release]
AID - 0665 [pii]
AID - 10.1128/jvi.77.18.9960-9968.2003 [doi]
PST - ppublish
SO  - J Virol. 2003 Sep;77(18):9960-8. doi: 10.1128/jvi.77.18.9960-9968.2003.