Initiation of hepatitis delta virus (HDV) replication: HDV RNA encoding the large delta antigen cannot replicate.
The hepatitis delta virus (HDV) nucleocapsid consists of a genomic-length RNA of 1.7 kb and approximately equimolar amounts of the small and large forms of the hepatitis delta antigen (S-HDAg and L-HDAg, respectively). Since HDV RNA particles contain not only a genomic RNA species encoding S-HDAg but also an RNA species encoding L-HDAg, which is produced by an RNA-editing process, the question arises as to whether RNAs encoding either L-HDAg or S-HDAg can initiate replication. To study this, two cDNA-free transfection methods were employed: HDV RNA cotransfected with either the S-HDAg-encoding mRNA species or the ribonucleocapsid protein complex, comprising HDV RNA and recombinant S-HDAg. Results showed that the genomic-sense RNA encoding S-HDAg could promote HDV replication, whereas the L-HDAg-encoding RNA species was unable to replicate under the same conditions. The antigenomic RNA species encoding either S-HDAg or L-HDAg could not replicate by either of these procedures. In addition, L-HDAg alone could not promote replication of the genomic RNA but, by supplementing an equal amount of S-HDAg, replication occurred. These data indicate that L-HDAg-encoding RNA species are probably not involved in the initiation of HDV RNA synthesis; instead, their main function may be to serve as template for producing L-HDAg, which regulates HDV RNA synthesis and virion assembly. These results suggest that the genomic RNA species encoding S-HDAg is the only functional genome for HDV infection and explain why the presence of the edited HDV RNA encoding L-HDAg does not interfere with HDV infection.
Sheu
Gwo-Tarng
GT
Institute of Toxicology, Chung Shan Medical University, 110 Sec. 1, Chien-Kuo N. Road, Taichung 40203, Taiwan, Republic of China1.
D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D018963:Hepatitis Antigens / Q000235:genetics* / Q000378:metabolism; D003698:Hepatitis Delta Virus / Q000235:genetics* / Q000502:physiology; D035923:Hepatitis delta Antigens; D016297:Mutagenesis, Site-Directed; D012367:RNA, Viral / Q000096:biosynthesis*; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D013698:Templates, Genetic; D014162:Transfection; D014779:Virus Replication / Q000502:physiology*
D018963:Hepatitis Antigens; D035923:Hepatitis delta Antigens; D012367:RNA, Viral; D016601:RNA-Binding Proteins; C442244:hepatitis delta virus large antigen