Evolution rate of hepatitis delta virus RNA isolated in Taiwan.
The complete RNA sequences of hepatitis delta viruses (HDV) isolated at 3 years apart from a chronic delta hepatitis patient in Taiwan were determined. The sequence analysis showed an overall evolution rate of 3.18 x 10(-3) substitutions/nucleotide/year. The evolution rates in different parts of HDV RNA varied. The hypervariable region evolved faster (4.55 x 10(-3) substitutions/nucleotide/year) than the hepatitis delta antigen (HDAg)-coding region (2.60 x 10(-3) substitutions/nucleotide/year) and the autocatalytic region (1.11 x 10(-3) substitutions/nucleotide/year). These data are compatible with the previous finding that the hypervariable region is more divergent than the HDAg-coding region and the autocatalytic regions among the HDV isolates from different geographic areas. No substitution was found in the four previously identified conserved domains of HDV RNA, further confirming their functional importance in viral replication. The evolution rate of this HDV RNA is higher than that determined from the partial RNA sequences of two Japanese HDV isolates and similar to that found in a Lebanon isolate. Further, it was found that this HDV RNA retained the same microheterogeneities at 15 nucleotide positions detected in the RNA 3 years earlier. It is concluded that HDV RNA in patients' serum is extremely heterogeneous, and that the nucleotide substitutions in certain nucleotide positions likely have conferred evolutionary advantages for HDV. Viral sequence evolution is a possible mechanism for chronic HDV infection.
Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China.
Y C
YC
Chao
H S
HS
Tang
C T
CT
Hsu
D000328:Adult; D000595:Amino Acid Sequence; D000956:Antigens, Viral / Q000235:genetics; D001483:Base Sequence; D005075:Biological Evolution; D002908:Chronic Disease; D018076:DNA, Complementary; D018740:Genetic Heterogeneity; D016679:Genome, Viral; D003699:Hepatitis D / Q000821:virology*; D003698:Hepatitis Delta Virus / Q000235:genetics*; D035923:Hepatitis delta Antigens; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013045:Species Specificity; D013624:Taiwan
D000956:Antigens, Viral; D018076:DNA, Complementary; D035923:Hepatitis delta Antigens; D012367:RNA, Viral; C442244:hepatitis delta virus large antigen