Discovery of a novel point mutation changing the HDAg expression of a hepatitis delta virus isolate from Central African Republic.
None of the mutations so far discovered in several hepatitis delta virus (HDV) isolates appears to determine important changes in HDV specific protein (HDAg) expression, except for a putative mutation at nucleotide 1012 converting an amber stop codon (TAG) to a codon for tryptophan (TGG). Here we present the characterization of an HDV obtained from the liver of a woodchuck inoculated with sera from fulminant HDV patients in Central African Republic (CAR). By restriction enzyme analysis and sequencing of HDAg-coding region cDNA clones, we found that this HDV isolate bears a novel mutation (T to A) at nucleotide 1013 which converts the amber stop codon (TAG) to a codon for lysine (AAG). Comparison of these nucleotide sequences with those available from American, Japanese, Taiwanese, French, Italian and Nauru isolates showed a variability of 1.7 to 21.5% and 1.9 to 28.7% at the nucleic acid and amino acid levels, respectively. The HDAg-encoding sequence of the CAR isolate is closely related to that of the Italian HDV isolate. The in vitro expression of this HDV isolate resulted in a unique HDAg species (28K) which was identical with that characterized in vivo.
Institut National de la Santé et de la Recherche Médicale (INSERM) U 271, Lyon, France.
J R
JR
Tang
O
O
Hantz
L
L
Vitvitski
J P
JP
Lamelin
R
R
Parana
L
L
Cova
J L
JL
Lesbordes
C
C
Trépo
D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000096:biosynthesis* / Q000235:genetics; D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D002488:Central African Republic; D003001:Cloning, Molecular; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification; D003698:Hepatitis Delta Virus / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D035923:Hepatitis delta Antigens; D006801:Humans; D008099:Liver / Q000382:microbiology; D008392:Marmota; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000235:genetics / Q000302:isolation & purification; D015183:Restriction Mapping; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid
D000956:Antigens, Viral; D004279:DNA, Viral; D035923:Hepatitis delta Antigens; D012367:RNA, Viral; C442244:hepatitis delta virus large antigen