| Hemorrhagic fever with renal syndrome(HFRS) is caused by Hantavirus, which is an acute infectious disease characterized by fever, vascular hemorrhage and kidney dysfunction. There are about 50 thousands to 100 thousands cases in China every year, which come to more than 90% throughout the world. The sufferers are at higher risk of death. It can't be cured effectively and prevented by safe vaccines.Hantaviruses are enveloped viruses which define a unique genus within the Bunyaviridae and contain a tripartite negative-stranded RNA genome. The gene segments S, M and L encode nucleocapsid protein NP, envolope glycoproteins GP (Gl and G2), and RNA dependent RNA polymerase (RDRP) respectively. GP is believed to mediate several important viral functions, suchas interact with target cell receptors and stimulate neutralizing antibodies by neutralizing antigen which mainly exist in G2; NP can induce strong humoral and cellular immunity, but it isn't defined that whether having neutralizing antigenic sites on NP. There are 9 serotypes of Hantavirus. The main types in our country are HTNV and SEOV, which is represented by 76-118 strain.All viruses initiate infection of susceptible cells by first binding to a cell surface receptor which triggered by the specific binding between virus attachment protein (VAP). If the binding between them is inhibited, we can prevent the viral infection. Viral receptors, existing on host cell membrane can be recognized and bound by VAP, and is a useful agent in assisting viral infection; VAP, existing in envelope glycoproteins of enveloped viruses, can not only mediate the specific binding between viruses and receptors of host cell membranes but have highly neutralizing capacity which is the target protein of neutralizing antibodies. At present there isn't definite description of the antigenic sites of Hantaviruses and receptors on host cells, so it is of great importance to identify the receptors and VAP to better understand the mechanism of viral infection and design the useful medicines and safe vaccines.The viral receptors have been studied for more than 40 years, and significant progresses have just been made in the past decade. Since the isolation of influenza virus receptors-sialic acids in the middle of 1980s, many different viral receptors have been identified. But limited by traditional methods, many viral receptors haven't been defined. The phage displayed peptide library technique provides a newly useful approach to study the viral receptors, and shows good perspective. The technique is based on the idea thatonly several amino acid play the major role in the interaction between two proteins. The latest research results reveal that the linear oligo-peptide expressed by phage can not only induce the same strong specific immunity just as the assembled epitope of the natural antigen does, but mimic the epitope including glycosyl or chemical-modificated peptides, that is so called "mimotope". Oligo-peptide containing mimotope with high antigenicity can substitute for large antigen segment to be used in the study of the structure and function of the key antigenic sites on viruses, and provide a valuable clue on prevention, diagnosis and treatment. The larger the library capacity is, the more likely to biopan positive clones.A radioligand binding assay of receptors was established by using anti-receptor serum and viral radio-label technique in our department, which indicated that the HTNV receptor might include trypsin-sensitive protein component and receptors on various HTNV-sensitivities cells shared conformational similarities.A HTNV type-specific mAb 3G1 could react to both HTNV glycoprotein G2 and nucleocapsid protein(NP) and possessed fairly high neutralizing and hemagglutination inhibiting titer and strong protective activity. It is speculated that mAb 3G1 is similar to HTNV receptor in tridimensional strcture or its neutralizing site is against VAP, then the mAb can inhibit or block the interaction with VAP and receptors by competation. In this resear... |
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