PMID- 10679075
OWN - NLM
STAT- MEDLINE
DCOM- 20000323
LR  - 20190515
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 164
IP  - 5
DP  - 2000 Mar 1
TI  - RANTES binding and down-regulation by a novel human herpesvirus-6 beta chemokine 
      receptor.
PG  - 2396-404
AB  - The human herpesvirus 6 (HHV-6) U51 gene defines a new family of 
      betaherpesvirus-specific genes encoding multiple transmembrane glycoproteins with 
      similarity to G protein-coupled receptors, in particular, human chemokine 
      receptors. These are distinct from the HHV-6 U12 and HCMV US28 family. In vitro 
      transcription and translation as well as transient cellular expression of U51 
      showed properties of a multiple transmembrane protein with a 30-kDa monomer as 
      well as high m.w. aggregates or oligomers. Transient cellularly expressed U51 
      also appeared to form dimeric intermediates. Despite having only limited sequence 
      similarity to chemokine receptors, U51 stably expressed in cell lines showed 
      specific binding of the CC chemokine RANTES and competitive binding with other 
      beta chemokines, such as eotaxin; monocyte chemoattractant protein 1, 3, and 4; 
      as well as the HHV-8 chemokine vMIPII. In epithelial cells already secreting 
      RANTES, U51 expression resulted in specific transcriptional down-regulation. This 
      correlated with reduced secretion of RANTES protein into the culture 
      supernatants. Regulation of RANTES levels may alter selective recruitment of 
      circulating inflammatory cells that the virus can infect and thus could mediate 
      the systemic spread of the virus from initial sites of infection in epithelia. 
      Alternatively, chemokine regulation could modulate a protective inflammatory 
      response to aid the spread of virus by immune evasion. Such mimicry, by viral 
      proteins, of host receptors leading to down-regulation of chemokine expression is 
      a novel immunomodulatory mechanism.
FAU - Milne, R S
AU  - Milne RS
AD  - Department of Infectious and Tropical Diseases, London School of Hygiene and 
      Tropical Medicine and Kings's College School of Medicine and Dentistry, 
      University of London, United Kingdom.
FAU - Mattick, C
AU  - Mattick C
FAU - Nicholson, L
AU  - Nicholson L
FAU - Devaraj, P
AU  - Devaraj P
FAU - Alcami, A
AU  - Alcami A
FAU - Gompels, U A
AU  - Gompels UA
LA  - eng
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 (Chemokine CCL5)
RN  - 0 (Chemokines, CC)
RN  - 0 (Ligands)
RN  - 0 (Receptors, Chemokine)
RN  - 0 (Receptors, Virus)
RN  - 0 (U51 protein, human herpesvirus 6)
RN  - 0 (Viral Proteins)
RN  - 0 (Viral Structural Proteins)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Cell Line
MH  - Chemokine CCL5/antagonists & inhibitors/biosynthesis/*metabolism
MH  - Chemokines, CC/*metabolism
MH  - *Down-Regulation/genetics
MH  - Epithelial Cells/metabolism/virology
MH  - GTP-Binding Proteins/genetics/metabolism
MH  - Genes, Viral
MH  - Herpesvirus 6, Human/genetics/*metabolism
MH  - Humans
MH  - K562 Cells
MH  - Ligands
MH  - Molecular Sequence Data
MH  - Protein Binding/genetics
MH  - Receptors, Chemokine/chemistry/genetics/*physiology
MH  - Receptors, Virus/chemistry/genetics/*physiology
MH  - Tumor Cells, Cultured
MH  - Viral Proteins/chemistry/genetics/physiology
MH  - Viral Structural Proteins/genetics
EDAT- 2000/02/29 09:00
MHDA- 2000/03/25 09:00
CRDT- 2000/02/29 09:00
PHST- 2000/02/29 09:00 [pubmed]
PHST- 2000/03/25 09:00 [medline]
PHST- 2000/02/29 09:00 [entrez]
AID - ji_v164n5p2396 [pii]
AID - 10.4049/jimmunol.164.5.2396 [doi]
PST - ppublish
SO  - J Immunol. 2000 Mar 1;164(5):2396-404. doi: 10.4049/jimmunol.164.5.2396.