RRC ID 36654
著者 Maeki T, Hayashi M, Kawabata A, Tang H, Yamanishi K, Mori Y.
タイトル Identification of the human herpesvirus 6A gQ1 domain essential for its functional conformation.
ジャーナル J Virol
Abstract Human herpesvirus 6 is a T lymphotropic herpesvirus, long classified into variants A and B (HHV-6A and HHV-6B) based on differences in sequence and pathogenicity. Recently, however, HHV-6A and HHV-6B were reclassified as different species. Here, we isolated a neutralizing monoclonal antibody (Mab) named AgQ 1-1 that was specific for HHV-6A glycoprotein Q1 (AgQ1), and we showed that amino acid residues 494 to 497 of AgQ1 were critical for its recognition by this Mab. This region was also essential for AgQ1's complex formation with gH, gL, and gQ2, which might be important for viral binding to the cellular receptor, CD46. In addition, amino acid residues 494 to 497 are essential for viral replication. Interestingly, this sequence corresponds to the domain on HHV-6B gQ1 that is critical for recognition by an HHV-6B-specific neutralizing Mab. Within this domain, only Q at position 496 of HHV-6A is distinct from the HHV-6B sequence; however, the mutant AgQ1(Q496E) was still clearly recognized by the Mab AgQ 1-1. Surprisingly, replacement of the adjacent amino acid, in mutant AgQ1(C495A), resulted in poor recognition by Mab AgQ 1-1, and AgQ1(C495A) could not form the gH/gL/gQ1/gQ2 complex. Furthermore, the binding ability of mutant AgQ1(L494A) with CD46 decreased, although it could form the gH/gL/gQ1/gQ2 complex and it showed clear reactivity to Mab AgQ 1-1. These data indicated that amino acid residues 494 to 497 of AgQ1 were critical for the recognition by Mab AgQ 1-1 and essential for AgQ1's functional conformation.
巻・号 87(12)
ページ 7054-63
公開日 2013-6-1
DOI 10.1128/JVI.00611-13
PII JVI.00611-13
PMID 23596294
PMC PMC3676137
MeSH Amino Acid Sequence Antibodies, Monoclonal / immunology* Antibodies, Neutralizing / immunology* Antibody Specificity* Glycoproteins / chemistry* Glycoproteins / immunology Glycoproteins / metabolism HEK293 Cells Herpesvirus 6, Human / immunology* Humans Molecular Sequence Data Protein Conformation Structure-Activity Relationship Viral Envelope Proteins / chemistry* Viral Envelope Proteins / immunology Viral Envelope Proteins / metabolism
IF 4.501
引用数 7
WOS 分野 VIROLOGY
リソース情報
研究用ヒト臍帯血幹細胞 研究用ヒト臍帯血幹細胞