Identification of a Novel Hepatitis C Virus Genotype From Punjab, India: Expanding Classification of Hepatitis C Virus Into 8 Genotypes

Borgia, Sergio; Hedskog, Charlotte; Parhy, Bandita; Hyland, Robert H.; Stamm, Luisa M.; Brainard, Diana M.; Subramanian, Mani; McHutchison, John G.; Mo, Hongmei; Svarovskaia, Evguenia S.; Shafran, Stephen D.

doi:10.1093/infdis/jiy401

Cited by 245 publications

(181 citation statements)

References 37 publications

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“…HCV belongs to the Hepacivirus genus in the Flaviviridae family and comprises eight genotypes with at least 86 subtypes [10,11]. The virus particle is enveloped and has a single-stranded positive-sense RNA genome of approximately 9.6 kb, coding for one single open-reading frame that gives rise to 10 mature viral proteins [12].…”

Section: Introductionmentioning

confidence: 99%

Gene Expression Profiling of Different Huh7 Variants Reveals Novel Hepatitis C Virus Host Factors

Dächert

Gladilin

Binder

2019

Viruses

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Chronic Hepatitis C virus (HCV) infection still constitutes a major global health problem with almost half a million deaths per year. To date, the human hepatoma cell line Huh7 and its derivatives is the only cell line that robustly replicates HCV. However, even different subclones and passages of this single cell line exhibit tremendous differences in HCV replication efficiency. By comparative gene expression profiling using a multi-pronged correlation analysis across eight different Huh7 variants, we identified 34 candidate host factors possibly affecting HCV permissiveness. For seven of the candidates, we could show by knock-down studies their implication in HCV replication. Notably, for at least four of them, we furthermore found that overexpression boosted HCV replication in lowly permissive Huh7 cells, most prominently for the histone-binding transcriptional repressor THAP7 and the nuclear receptor NR0B2. For NR0B2, our results suggest a finely balanced expression optimum reached in highly permissive Huh7 cells, with even higher levels leading to a nearly complete breakdown of HCV replication, likely due to a dysregulation of bile acid and cholesterol metabolism. Our unbiased expression-profiling approach, hence, led to the identification of four host cellular genes that contribute to HCV permissiveness in Huh7 cells. These findings add to an improved understanding of the molecular underpinnings of the strict host cell tropism of HCV.

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Section: Introductionmentioning

confidence: 99%

Gene Expression Profiling of Different Huh7 Variants Reveals Novel Hepatitis C Virus Host Factors

Dächert

Gladilin

Binder

2019

Viruses

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“…To date, seven genotypes of HCV have been identified through phylogenetic analysis, which are further subdivided into 84 subtypes, many of which were identified in high‐income countries (HICs) . Additionally, four sequences recently identified in India appear to fulfill the criteria for g8 . The open reading frames (ORFs) of HCV genotypes differ from each other by at least 30% at the nucleotide level, whereas those of subtypes differ by 10%‐25% .…”

mentioning

confidence: 99%

“…(6) Additionally, four sequences recently identified in India appear to fulfill the criteria for g8. (7) The open reading frames (ORFs) of HCV genotypes differ from each other by at least 30% at the nucleotide level, whereas those of subtypes differ by 10%-25%. (6) The genome consists of single-stranded positive-sense RNA with 5′ and 3′ untranslated regions (UTRs) and 10 genes that encode structural proteins and nonstructural proteins (NSs) (core, envelope E1 and E2, p7, NS2, NS3, NS4A, NS4B, NS5A, and NS5B).…”

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confidence: 99%

Highly Diverse Hepatitis C Strains Detected in Sub‐Saharan Africa Have Unknown Susceptibility to Direct‐Acting Antiviral Treatments

et al. 2019

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The global plan to eradicate hepatitis C virus (HCV) led by the World Health Organization outlines the use of highly effective direct‐acting antiviral drugs (DAAs) to achieve elimination by 2030. Identifying individuals with active disease and investigation of the breadth of diversity of the virus in sub‐Saharan Africa (SSA) is essential as genotypes in this region (where very few clinical trials have been carried out) are distinct from those found in other parts of the world. We undertook a population‐based, nested case‐control study in Uganda and obtained additional samples from the Democratic Republic of Congo (DRC) to estimate the prevalence of HCV, assess strategies for disease detection using serological and molecular techniques, and characterize genetic diversity of the virus. Using next‐generation and Sanger sequencing, we aimed to identify strains circulating in East and Central Africa. A total of 7,751 Ugandan patients were initially screened for HCV, and 20 PCR‐positive samples were obtained for sequencing. Serological assays were found to vary significantly in specificity for HCV. HCV strains detected in Uganda included genotype (g) 4k, g4p, g4q, and g4s and a newly identified unassigned g7 HCV strain. Two additional unassigned g7 strains were identified in patients originating from DRC (one partial and one full open reading frame sequence). These g4 and g7 strains contain nonstructural (ns) protein 3 and 5A polymorphisms associated with resistance to DAAs in other genotypes. Clinical studies are therefore indicated to investigate treatment response in infected patients. Conclusion : Although HCV prevalence and genotypes have been well characterized in patients in well‐resourced countries, clinical trials are urgently required in SSA, where highly diverse g4 and g7 strains circulate.

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“…A consistent, unified approach to classification will advance this field, improving consistency of curating, archiving and reporting sequence data. Recent work sampling poorly accessed populations has uncovered numerous new HCV isolates (41,42), and the diversity of sequences generated for HBV may expand in a similar way. The use of a robust and consistent classification system will also be important in screening new populations for potentially novel HBV isolates.…”

Section: Resultsmentioning

confidence: 99%

Analysis of genomic-length HBV sequences to determine genotype and subgenotype reference sequences

McNaughton

Revill

Matthews

et al. 2019

Preprint

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Hepatitis B virus (HBV) is a diverse, partially double-stranded DNA virus, with 9 genotypes (A-I), and a putative 10th genotype (J), thus far characterised. Given the broadening interest in HBV sequencing, there is an increasing requirement for a consistent, unified approach to HBV genotype and subgenotype classification. We set out to generate an updated resource of reference sequences using the diversity of all genomic-length HBV sequences available in public databases. We collated and aligned genomic-length HBV sequences from public databases and used maximum-likelihood phylogenetic analysis to identify genotype clusters. Within each genotype, we examined the phylogenetic support for currently defined subgenotypes, as well as identifying well-supported clades and deriving reference sequences for them. An alignment of these reference sequences and maximum-likelihood phylogenetic trees of the sequences are provided to simplify classification. Based on the phylogenies generated, we present a comprehensive set of HBV reference sequences at the genotype and subgenotype level.

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Identification of a Novel Hepatitis C Virus Genotype From Punjab, India: Expanding Classification of Hepatitis C Virus Into 8 Genotypes

Abstract: The discovery of a novel HCV GT8 confirms the circulation of this newly identified lineage in the human population.

Cited by 245 publications

References 37 publications

Gene Expression Profiling of Different Huh7 Variants Reveals Novel Hepatitis C Virus Host Factors

Gene Expression Profiling of Different Huh7 Variants Reveals Novel Hepatitis C Virus Host Factors

Highly Diverse Hepatitis C Strains Detected in Sub‐Saharan Africa Have Unknown Susceptibility to Direct‐Acting Antiviral Treatments

Analysis of genomic-length HBV sequences to determine genotype and subgenotype reference sequences

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