A new class of defective hepatitis B virus genomes with an internal poly(dA) sequence.
Sequence heterogeneity of hepatitis B virus (HBV) is increasingly recognized to play a role in virus-host interaction. We have used a recently established method for HBV full-length genome amplification to search for novel types of HBV variants and to investigate further the sequence heterogeneity of HBV genome populations. Using this method, a substantial fraction of HBV genomes much shorter than wildtype size was found in some sera and liver biopsies from infected patients. Cloning and sequencing of a number of these HBV genomes as well as hybridization studies revealed a new minor class of HBV genomes with an internal poly(dA) sequence approximately 60 to more than 100 nucleotides long in 4 of 10 patients. The 5'-ends of the internal poly(dA) sequences are located at positions corresponding to the authentic processing/polyadenylation sites of the RNA pregenome, whereas the positions of the 3'-ends are variable due to different sizes of adjacent deletions. These data suggest that the poly(A) tail of the pregenomic RNA is occasionally reverse transcribed by the HBV P-protein and during this process a deletion seems to be introduced into the DNA minus strand. We propose a mechanism by which this could be accomplished during DNA minus strand synthesis.
Sommer
G
G
Heinrich-Pette-Institut für experimentalle Virologie und immunologie an, Universität Hamburg, Germany.
Günther
S
S
Sterneck
M
M
Otto
S
S
Will
H
H
D001483:Base Sequence; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics*; D003673:Defective Viruses / Q000235:genetics*; D016679:Genome, Viral; D006509:Hepatitis B / Q000821:virology*; D006515:Hepatitis B virus / Q000235:genetics* / Q000502:physiology; D006521:Hepatitis, Chronic / Q000821:virology; D006801:Humans; D008099:Liver / Q000821:virology*; D011061:Poly A / Q000032:analysis*; D019914:Taq Polymerase / Q000378:metabolism; D013698:Templates, Genetic; D014162:Transfection; D014766:Viremia / Q000821:virology*; D014779:Virus Replication
D004279:DNA, Viral; D011061:Poly A; C015465:poly(dA); D019914:Taq Polymerase