The Study of the Factors that May Affect the Package Efficiency of Hepatitis D Virus

• Main Authors: Ya-Li Kuo, 郭雅莉
• Other Authors: Wan-Jr Syu
• Format: Others
• Language: zh-TW
• Published: 2000
• Online Access: http://ndltd.ncl.edu.tw/handle/50896073961752019340

碩士 === 國立陽明大學 === 微生物暨免疫學研究所 === 88 === Hepatitis delta virus (HDV) is a defective RNA virus. The envelope of HDV is composed of surface proteins (HBsAg) from hepatitis B virus. Inside the HDV particle there are the HDV single stranded, covalently closed circular RNA genome and the only known virus-encoded protein, the hepatitis delta antigen (HDAg). HDAg has two forms of a single protein, the small (S-HDAg) and large (L-HDAg) forms, which are identical in sequence except that L-HDAg contains 19 extra amino acids at its C-terminus. While S-HDAg is required for viral replication, L-HDAg suppresses the replication and is critical for viral packaging. The last C-terminal 4 amino acids, CXXX, of L-HDAg contain an isoprenylation motif. Previously it has been shown that isoprenylation of L-HDAg is necessary for HDV assembly and mediates the protein-protein interaction between L-HDAg and the HBsAg of HBV. A recent observation in our lab, the virus package efficiency differs between genotypes, and L-HDAg of genotype I is apparently more efficiently assembled than that of genotype II. It has been known that the isoprenylation is necessary for package but the study of isoprenylation of L-HDAg is only limited on genotype I. Genotype I L-HDAg is farnesylated and how that of genotype II is modified remains unknown. We analyzed the isoprenoids extracted from two strains of genotype II and one strain of genotype I. The data showed that L-HDAg of both genotypes are farnesylated. Therefore, we ruled out the possibility that different isoprenyl modifications affect package efficiency. Thus, whether these different L-HDAg molecules have varied levels of farnesylation was addressed. The data showed that the farnesylation level of genotype I is generally higher than that of genotype II. Therefore we concluded that farnesylation level is one of the factors that may affect the virus package efficiency.