PMID- 16365449
OWN - NLM
STAT- MEDLINE
DCOM- 20060216
LR  - 20220129
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 176
IP  - 1
DP  - 2006 Jan 1
TI  - Identification and characterization of U83A viral chemokine, a broad and potent 
      beta-chemokine agonist for human CCRs with unique selectivity and inhibition by 
      spliced isoform.
PG  - 544-56
AB  - Leukotropic human herpesvirus 6 (HHV-6) establishes a persistent infection 
      associated with inflammatory diseases and encodes chemokines that could 
      chemoattract leukocytes for infection or inflammation. HHV-6 variant A encodes a 
      distant chemokine homolog, U83A, and a polymorphism promoting a secreted form was 
      identified. U83A and three N-terminal modifications were expressed and purified, 
      and activities were compared with a spliced truncated isoform, U83A-Npep. U83A 
      efficiently and potently induced calcium mobilization in cells expressing single 
      human CCR1, CCR4, CCR6, or CCR8, with EC50 values <10 nM. U83A also induced 
      chemotaxis of Th2-like leukemic cells expressing CCR4 and CCR8. High-affinity 
      binding, 0.4 nM, was demonstrated to CCR1 and CCR5 on monocytic/macrophage cells, 
      and pretreatment with U83A or modified forms could block responses for endogenous 
      ligands. U83A-Npep acted only as antagonist, efficiently blocking binding of CCL3 
      to CCR1 or CCR5 on differentiated monocytic/macrophage leukemic cells. 
      Furthermore, CCL3 induction of calcium signaling via CCR1 and CCL1 induced 
      chemotaxis via CCR8 in primary human leukocytes was inhibited. Thus, this 
      blocking by the early expressed U83A-Npep could mediate immune evasion before 
      finishing the replicative cycle. However, late in infection, when full-length 
      U83A is made, chemoattraction of CCR1-, CCR4-, CCR5-, CCR6-, and CCR8-bearing 
      monocytic/macrophage, dendritic, and T lymphocyte cells can facilitate 
      dissemination via lytic and latent infection of these cells. This has further 
      implications for neuroinflammatory diseases such as multiple sclerosis, where 
      both cells bearing CCR1/CCR5 plus their ligands, as well as HHV-6A, have been 
      linked. Applications also discussed include novel vaccines/immunotherapeutics for 
      cancer and HIV as well as anti-inflammatories.
FAU - Dewin, David R
AU  - Dewin DR
AD  - Department of Infectious and Tropical Diseases, London School of Hygiene and 
      Tropical Medicine, University of London, London, United Kingdom.
FAU - Catusse, Julie
AU  - Catusse J
FAU - Gompels, Ursula A
AU  - Gompels UA
LA  - eng
GR  - BBS/B/02231/BB_/Biotechnology and Biological Sciences Research Council/United 
      Kingdom
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Chemokines)
RN  - 0 (DNA, Recombinant)
RN  - 0 (Protein Isoforms)
RN  - 0 (Receptors, Chemokine)
RN  - 0 (U83 protein, Human herpesvirus 6)
RN  - 0 (Viral Proteins)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Cell Line
MH  - Chemokines/*genetics/*immunology/*metabolism
MH  - Chemotaxis, Leukocyte
MH  - Chromatography, High Pressure Liquid
MH  - DNA, Recombinant
MH  - Dendritic Cells/immunology/metabolism
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Flow Cytometry
MH  - Genes, Viral/*genetics/immunology
MH  - Herpesvirus 6, Human/physiology
MH  - Humans
MH  - Image Processing, Computer-Assisted
MH  - Leukocytes, Mononuclear/immunology/metabolism
MH  - Protein Isoforms/genetics/immunology
MH  - Receptors, Chemokine/*immunology
MH  - Th2 Cells/immunology/metabolism
MH  - Viral Proteins/*genetics/*immunology/*metabolism
EDAT- 2005/12/21 09:00
MHDA- 2006/02/17 09:00
CRDT- 2005/12/21 09:00
PHST- 2005/12/21 09:00 [pubmed]
PHST- 2006/02/17 09:00 [medline]
PHST- 2005/12/21 09:00 [entrez]
AID - 176/1/544 [pii]
AID - 10.4049/jimmunol.176.1.544 [doi]
PST - ppublish
SO  - J Immunol. 2006 Jan 1;176(1):544-56. doi: 10.4049/jimmunol.176.1.544.