Structure and organization of the hepatitis C virus genome isolated from human carriers

Takamizawa, Akihisa; Mori, Chisato; Fuke, Isao; Manabe, Sadao; Murakami, Shigeki; Fujita, Junji; Onishi, E; Andoh, T; Yoshida, Iwao; Okayama, Hiroto

doi:10.1128/jvi.65.3.1105-1113.1991

Cited by 900 publications

(339 citation statements)

References 30 publications

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“…The sequence of the HepCV RNA genome has been determined via sequencing of cDNAs [ 13,27,29,44]. Initially a random-primed expression cDNA library in X gttl was prepared from RNA extracted from infectious material concentrated from a large volume of high titer plasma from a chimpanzee (see above) with a chronic NANBH infection.…”

Section: Initial Identification and Cdna Cloning Of Hepcv Rata And Dementioning

confidence: 99%

“…Recently, consensus sequences have also been reported for two HepCV genomes isolated from pooled plasma of nine Japanese NANBH patients (referred to as HepCV-J) [29] and of fifty Japaneses blood donors with elevated plasma ALT activity (referred to as HepCV-KB) [44]. In both studies virus particles were collected from plasma by ultracentrifugation, RNA was extracted from pelleted material and reverse transcribed and cDNA libraries prepared in k~ gttl.…”

Section: Genome Sequence Analysesmentioning

confidence: 99%

“…In one study, the viral RNA was reverse transcribed using appropriate antisense oligonucleotides as primers or the viral RNA was polyadenylated and reverse transcribed using oligo(dT) as primer [29]. In the other study, viral RNA was reverse transcribed using random hexanucleotide primers [44]. The 9413 nucleotides long sequence of HepCV-J RNA contains 5'-and 3'-terminal untranslated segments of 329 and 54 nucleotides in length, respectively (Table 1).…”

Section: Genome Sequence Analysesmentioning

confidence: 99%

“…Another interpretation of the reported HepCV genomic sequences is that only the first 114 amino acids make up the nucleocapsid protein, that the next approximately 80 amino acids represent a matrix (M) protein, that E 1 is the single envelope glycoprotein of HepCV and that E 2/NS 1 is a non-structural protein [44]. This genome organization would be equivalent to that of the flaviviruses, except that the pre-M segment would be deleted.…”

Section: Potential Gene Productsmentioning

confidence: 99%

“…1). Overall, however, the amino acid sequence of HepCV-1 is only distantly related to those of the flaviviruses and pestiviruses [13,27,33,44]. Because of these differences but otherwise great similarities in genome organization and viron properties, HepCV has been suggested to be classified as a new genus within the family Flaviviridae [9,13,44].…”

Section: Potential Gene Productsmentioning

confidence: 99%

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Hepatitis C virus

Plagemann

1991

Archives of Virology

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HepCV is the major cause of NANB PT hepatitis and is also implicated as the cause in a large proportion of sporadic cases of NANBH. Chronic infection with HepCV has also been linked to the development of hepatocellular carcinoma. Chimpanzees and marmosets are the only animals found to be experimentally infectable and the virus has not been propagated in any cell culture system. HepCV is an enveloped virus with a diameter of 30-60 nm and a 10-kb positive-stranded RNA genome. Its genome organization resembles that of the flaviviruses and pestiviruses. A 5'-untranslated segment of 341 nucleotides precedes a continuous ORF of 9030/9033 nucleotides which is followed by a 54 nucleotides long 3'-non-coding segment. Further work is required to resolve the question of whether the genomic RNA possesses a 3'-poly(U) or poly(A) tail. The genome also carries an internal poly(A) segment towards the 5'-end of its ORF. Genomic RNA is probably translated into a single polyprotein of 3010/3011 amino acids which is processed into functional proteins. The viral proteins have not been identified, but on the basis of the predicted amino acid sequences, hydrophobicity plots, location of potential glycosylation sites and similarities of these properties to those of pesti- and flaviviruses, the following genome organization has been predicted. The predicted viral structural proteins, a nucleocapsid protein and two envelope glycoproteins are located at the amino-terminal end of the polyprotein. They are followed by a highly hydrophobic protein and proteins that exhibit proteinase, helicase and replicase domains and thus are probably involved in RNA replication and protein processing. The replicase domain is located close to the carboxy terminus of the polyprotein. Although the overall nucleotide and amino acid homologies between HepCV and pestiviruses are low, a number of similarities exist that point to a closer ancestral relationship to the latter than the flaviviruses. First, the 5'-untranslated segment of the HepCV genome resembles that of the pestivirus genomes in size and presence of several short ORFs and it contains several segments with high nucleotide homology. Second, the two putative envelope glycoproteins of HepCV resemble two of the three putative envelope glycoproteins of the pestiviruses. Because its genome organization and predicted virion structure closely resemble those of the flaviviruses and pestiviruses, HepCV has been proposed to be placed in the family Flaviviridae.(ABSTRACT TRUNCATED AT 400 WORDS)

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Section: Initial Identification and Cdna Cloning Of Hepcv Rata And Dementioning

confidence: 99%

Section: Genome Sequence Analysesmentioning

confidence: 99%

Section: Genome Sequence Analysesmentioning

confidence: 99%

Section: Potential Gene Productsmentioning

confidence: 99%

Section: Potential Gene Productsmentioning

confidence: 99%

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Hepatitis C virus

Plagemann

1991

Archives of Virology

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Risk of Hepatitis C Virus Transmission From an Infected Gynecologist to Patients<subtitle>Results of a 7-Year Retrospective Investigation</subtitle>

Roß¹

2002

Arch Intern Med

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Persistence of hepatitis C virus RNA in established human hepatocellular carcinoma cell lines

Tsuboi

Nagamori

Miyazaki³

et al. 1996

J. Med. Virol.

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The persistence of the viral RNA of hepatitis C virus (HCV) was examined in 13 hepatocellular carcinoma (HCC) and two hepatoblastoma cell lines by reverse transcription followed by the polymerase chain reaction (RT-PCR). HCV RNA was detected in three HCC lines (JHH-1, JHH-4, and JHH-6) and negative-strand viral RNA was found in JHH-4, indicating that there is a putative replicative intermediate of HCV in JHH-4 cells. To rule out the possibility of contamination, the partial nucleotide sequences of HCV-specific PCR products of these three cell lines were determined. The clone from JHH-1 belonged to genotype 1 (1a or 1b), and the clones from JHH-4 and JHH-6 belonged to genotype 2b, but their sequences differed from each other. These cell lines may be useful for studies related to HCV.

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Structure and organization of the hepatitis C virus genome isolated from human carriers

Cited by 900 publications

References 30 publications

Hepatitis C virus

Hepatitis C virus

Risk of Hepatitis C Virus Transmission From an Infected Gynecologist to Patients<subtitle>Results of a 7-Year Retrospective Investigation</subtitle>

Persistence of hepatitis C virus RNA in established human hepatocellular carcinoma cell lines

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