Characterization of hepatitis C virus deletion mutants circulating in chronically infected patients.
Hepatitis C virus (HCV) has a linear positive-stranded RNA genome of approximately 9,600 nucleotides in length and displays a high level of sequence diversity caused by high mutation rates and recombination. However, when we performed long distance reverse transcription-PCRs on HCV RNA isolated from serum of chronic HCV patients, not only full-length HCV genomes but also HCV RNAs which varied in size from 7,600 to 8,346 nucleotides and contained large in-frame deletions between E1 and NS2 were amplified. Carefully designed control experiments indicated that these deletion mutants are a bona fide natural RNA species, most likely packaged in virions. Moreover, deletion mutants were detected in sera of patients infected with different HCV genotypes. We observed that 7/37 (18.9%) of genotype 1, 5/43 (11.6%) of genotype 3, and 4/13 (30.7%) of genotype 6 samples contained HCV deletion mutant genomes. These observations further exemplify HCV's huge genetic diversity and warrant studies to explore their biological relevance.
Noppornpanth
Suwanna
S
Department of Virology, Erasmus Medical Center, Dr Molewaterplein 50, 3015 GE, Rotterdam, The Netherlands.
Smits
Saskia L
SL
Lien
Truong Xuan
TX
Poovorawan
Yong
Y
Osterhaus
Albert D M E
AD
Haagmans
Bart L
BL
D001483:Base Sequence; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics* / Q000302:isolation & purification; D019698:Hepatitis C, Chronic; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D012367:RNA, Viral / Q000097:blood / Q000235:genetics* / Q000302:isolation & purification; D017423:Sequence Analysis, RNA; D017384:Sequence Deletion; D014759:Viral Envelope Proteins / Q000235:genetics
C087035:E1 protein, Hepatitis C virus; D012367:RNA, Viral; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus