PMID- 12171934
OWN - NLM
STAT- MEDLINE
DCOM- 20021219
LR  - 20210206
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 277
IP  - 42
DP  - 2002 Oct 18
TI  - Human Herpesvirus 6 and Measles Virus Employ Distinct CD46 Domains for Receptor 
      Function.
PG  - 39112-8
AB  - We employed a quantitative cell fusion assay to identify structural domains of 
      CD46 required for its function as a receptor for human herpesvirus 6 (HHV-6). We 
      examined the activities of recombinant variants of CD46, including different 
      isoforms as well as engineered truncations and molecular chimeras with 
      decay-accelerating factor, a related protein in the family of regulators of 
      complement activation (RCA). We observed strong receptor activity for all four 
      CD46 isoforms, which differ in the membrane-proximal extracellular and 
      cytoplasmic domains, indicating that the critical determinants for HHV-6 receptor 
      activity reside outside the C-terminal portion of CD46. Analysis of the short 
      consensus repeat (SCR) regions that comprise most of the extracellular portion of 
      CD46 indicated a strong dependence on SCRs 2 and 3 and no requirement for SCRs 1 
      or 4. Fusion-inhibition studies with SCR-specific monoclonal antibodies supported 
      the essential role of SCRs 2 and 3 in HHV-6 receptor activity. These findings 
      contrast markedly with fusion mediated by measles virus glycoproteins for which 
      we observed a strict dependence on SCRs 1 and 2, consistent with previous 
      reports. These results expand the emerging notion that CD46 and other members of 
      the RCA family are co-opted in distinct manners by different infectious 
      pathogens.
FAU - Greenstone, Heather L
AU  - Greenstone HL
AD  - NIAID, National Institutes of Health, Bethesda, Maryland 20892, USA.
FAU - Santoro, Fabio
AU  - Santoro F
FAU - Lusso, Paolo
AU  - Lusso P
FAU - Berger, Edward A
AU  - Berger EA
LA  - eng
PT  - Journal Article
DEP - 20020808
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antigens, CD)
RN  - 0 (CD46 protein, human)
RN  - 0 (Mcp protein, mouse)
RN  - 0 (Membrane Cofactor Protein)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Protein Isoforms)
RN  - 0 (Receptors, Virus)
SB  - IM
MH  - 3T3 Cells
MH  - Animals
MH  - Antibodies, Monoclonal
MH  - Antigens, CD/*biosynthesis/chemistry
MH  - Cells, Cultured
MH  - Chromosome Mapping
MH  - Complement Activation
MH  - Dose-Response Relationship, Drug
MH  - Flow Cytometry
MH  - HeLa Cells
MH  - Herpesvirus 6, Human/*metabolism
MH  - Humans
MH  - Lac Operon
MH  - Measles virus/*genetics
MH  - Membrane Cofactor Protein
MH  - Membrane Glycoproteins/*biosynthesis/chemistry
MH  - Mice
MH  - Plasmids/metabolism
MH  - Protein Binding
MH  - Protein Isoforms
MH  - Protein Structure, Tertiary
MH  - Receptors, Virus/*chemistry/metabolism
EDAT- 2002/08/13 10:00
MHDA- 2002/12/20 04:00
CRDT- 2002/08/13 10:00
PHST- 2002/08/13 10:00 [pubmed]
PHST- 2002/12/20 04:00 [medline]
PHST- 2002/08/13 10:00 [entrez]
AID - S0021-9258(19)72262-5 [pii]
AID - 10.1074/jbc.M206488200 [doi]
PST - ppublish
SO  - J Biol Chem. 2002 Oct 18;277(42):39112-8. doi: 10.1074/jbc.M206488200. Epub 2002 
      Aug 8.