Sequence variation in hepatitis C viral isolates

Weiner, Amy J.; Christopherson, Cindy; Hall, John; Bonino, Ferruccio; Saracco, Giorgio Maria; Brunetto, Maurizia Rossana; Crawford, Kevin; Marion, Christopher D.; Crawford, Kenneth A.; Venkatakrishna, Shyamala; Miyamura, Tatsuo; McHutchinson, John G.; Cuypers, Theo; Houghton, Michael

doi:10.1016/0168-8278(91)90015-4

Cited by 59 publications

(38 citation statements)

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“…Peptides A1H, A2H, and CH were copied from the H strain, and peptides A1a, A2a, and Ca were derived from a closely related subtype 1a strain. 26 Four peptides mapped within the E2A insert: A1H (ETHVTGGNAGRTTAGPVGLLTPGAKQNI) and A1a (ETHTTGGAAAKALFGFTNFWSQGPSQN), corresponding to aa 384-411 and encompassing the HVR 29 (peptides displayed 43% homology), A2H (IQLINTNGSWHINSTALNCNESLNTGWL) and A2a (IQLINTDGSWHINRTALNCNASHNTGW), corresponding to aa 411-437 (peptides displayed 85% homology). Two peptides mapped within the E2C insert: CH (TTDRSGAPTYSWGANDTD-VFV) and Ca (TTDKAGAPTYNWGSNDTDVFV), corresponding to aa 518-538 (peptides displayed 81% homology).…”

Section: Methodsmentioning

confidence: 99%

“…Although our DNA-based immunization approach was successful, the difficulty in inducing a broad immune response targeted at a region that apparently contains an important neutralizing domain but that is the most variable one found in the genome remains. 29 Whatever the injection mode (i.m. or i.e.)…”

Section: Dna-based Immunization First Demonstrated By Tang Et Al Inmentioning

confidence: 99%

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Modulation of immune responses to hepatitis C virus envelope E2 protein following injection of plasmid DNA using single or combined delivery routes

et al. 1998

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Section: Methodsmentioning

confidence: 99%

Section: Dna-based Immunization First Demonstrated By Tang Et Al Inmentioning

confidence: 99%

Modulation of immune responses to hepatitis C virus envelope E2 protein following injection of plasmid DNA using single or combined delivery routes

et al. 1998

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“…The quasispecies distribution of HCV might have important biological consequences (5,6). It has been proposed that this genetic heterogeneity allows HCV to escape immune pressure and to establish chronic infection (7)(8)(9)(10). In addition, the existence of a heterogeneous population of HCV may influence the outcome of antiviral therapy (11)(12)(13); resistance to treatment might result from selection of minor viral populations during this therapy.…”

mentioning

confidence: 99%

How Escherichia coli can bias the results of molecular cloning: Preferential selection of defective genomes of hepatitis C virus during the cloning procedure

Forns

Bukh

Purcell

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

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Cloned PCR products containing hepatitis C virus (HCV) genomic fragments have been used for analyses of HCV genomic heterogeneity and protein expression. These studies assume that the clones derived are representative of the entire virus population and that subsets are not inadvertently selected. The aim of the present study was to express HCV structural proteins. However, we found that there was a strong cloning selection for defective genomes and that most clones generated initially were incapable of expressing the HCV proteins. The HCV structural region (C-E1-E2-p7) was directly amplified by long reverse transcription-PCR from the plasma of an HCV-infected patient or from a control plasmid containing a viable full-length cDNA of HCV derived from the same patient but cloned in a different vector. The PCR products were cloned into a mammalian expression vector, amplified in Escherichia coli, and tested for their ability to produce HCV structural proteins. Twenty randomly picked clones derived from the HCV-infected patient all contained nucleotide mutations leading to absence or truncation of the expected HCV products. Of 25 clones derived from the control plasmid, only 8% were fully functional for polyprotein synthesis. The insertion of extra nucleotides in the region just upstream of the start codon of the HCV insert led to a statistically significant increase in the number of fully functional clones derived from the patient (42%) and from the control plasmid (72-92%). Nonrandom selection of clones during the cloning procedure has enormous implications for the study of viral heterogeneity, because it can produce a false spectrum of genomic diversity. It can also be an impediment to the construction of infectious viral clones.

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“…5 In addition to genotypes, HCV exists within its hosts as a pool of genetically distinct but closely related variants referred to as quasispecies. 6 While there is limited knowledge about the immunogenicity of HCV, it is widely expected that both the generation of escape and resistance mutations and the high variability itself will create formidable problems for drug and vaccine design. 7 This paper discusses three HCV databases available worldwide, in order of seniority: the Japanese HCV map and phylogeny database, the European HCV sequence and molecular models database and the Los Alamos HCV sequence and immunology databases.…”

mentioning

confidence: 99%

Hepatitis C databases, principles and utility to researchers

Kuiken¹,

Mizokami²,

Deléage³

et al. 2006

Hepatology

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Part of the effort to develop hepatitis C-specific drugs and vaccines is the study of genetic variability of all publicly available HCV sequences. Three HCV databases are currently available to aid this effort and to provide additional insight into the basic biology, immunology, and evolution of the virus. The Japanese HCV database (http:// s2as02.genes.nig.ac.jp) gives access to a genomic mapping of sequences as well as their phylogenetic relationships. The European HCV database (http://euhcvdb.ibcp.fr) offers access to a computer-annotated set of sequences and molecular models of HCV proteins and focuses on protein sequence, structure and function analysis. T he hepatitis C virus (HCV) has infected approximately 170 million people worldwide. HCV infection is cleared in about 25% of cases, 1,2 and in the rest results in chronic infection. Chronic HCV infection can lead to cirrhosis and liver cancer, and is the leading cause of liver transplantation in the United States. A recent Canadian study 3 estimated that lifetime HCV-associated mortality is around 1 in 8; a much larger number (an estimated 1 in 4) will develop cirrhosis of the liver. Most likely this number will be higher in less developed countries. With 170 million people infected worldwide, this means 20 million HCVrelated deaths in the next few decades.HCV is a positive-sense RNA virus with a genome of Ϸ10 kb, which encodes a single polyprotein of Ϸ3000 amino acids (aa) that is cleaved into three structural proteins (core, Envelope E1 and E2), the p7 protein whose function has not been determined, and six non-structural proteins (NS2, NS3, NS4A, NS4B, NS5A and NS5B). It has been classified as a hepacivirus, in of the Flaviviridae family, which also includes flaviviruses (West Nile, Japanese encephalitis and yellow fever viruses) and pestiviruses (bovin viral diarrhea and hog cholera virus). HCV shares some structural features with these viruses. However, the genetic distance between HCV and other flaviviruses is large enough that HCV cannot be meaningfully aligned to its flavivirus "relatives" over its entire genome 4 (also see http://hcv.lanl.gov/content/hcv-db/GET_ALIGNMENTS/ flavi-align.html), and it also shares structural features with the pestivirus family.HCV is subdivided into six genotypes and about 80 subtypes on the basis of nucleotide sequence identity. 5 In addition to genotypes, HCV exists within its hosts as a pool of genetically distinct but closely related variants referred to as quasispecies. 6 While there is limited knowledge about the immunogenicity of HCV, it is widely expected that both the generation of escape and resistance mutations and the high variability itself will create formidable problems for drug and vaccine design. 7 This paper discusses three HCV databases available worldwide, in order of seniority: the Japanese HCV map and phylogeny database, the European HCV sequence and molecular models database and the Los Alamos HCV sequence and immunology databases. We will first describe the three databases, highlighting comm...

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Sequence variation in hepatitis C viral isolates

Cited by 59 publications

References 14 publications

Modulation of immune responses to hepatitis C virus envelope E2 protein following injection of plasmid DNA using single or combined delivery routes

Modulation of immune responses to hepatitis C virus envelope E2 protein following injection of plasmid DNA using single or combined delivery routes

How Escherichia coli can bias the results of molecular cloning: Preferential selection of defective genomes of hepatitis C virus during the cloning procedure

Hepatitis C databases, principles and utility to researchers

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