Expression and characterization of a minimal hepatitis C virus glycoprotein E2 core domain that retains CD81 binding.
The hepatitis C virus glycoprotein E2 receptor-binding domain is encompassed by amino acids 384 to 661 (E2(661)) and contains two hypervariable sequences, HVR1 and HVR2. E2 sequence comparisons revealed a third variable region, located between residues 570 and 580, that varies widely between genotypes, designated here as igVR, the intergenotypic variable region. A secreted E2(661) glycoprotein with simultaneous deletions of the three variable sequences retained its ability to bind CD81 and conformation-dependent monoclonal antibodies (MAbs) and displayed enhanced binding to a neutralizing MAb directed to E2 immunogenic domain B. Our data provide insights into the E2 structure by suggesting that the three variable regions reside outside a conserved E2 core.
McCaffrey
Kathleen
K
Macfarlane Burnet Institute for Medical Research and Public Health, 85 Commercial Rd., Melbourne, Australia.
Boo
Irene
I
Poumbourios
Pantelis
P
Drummer
Heidi E
HE
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000378:metabolism; D000914:Antibodies, Viral / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism*; D001665:Binding Sites / Q000235:genetics; D016174:Hepacivirus / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011991:Receptors, Virus / Q000378:metabolism; D017384:Sequence Deletion; D060225:Tetraspanin 28; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D015703:Antigens, CD; C554798:CD81 protein, human; D011991:Receptors, Virus; D060225:Tetraspanin 28; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus