The 2005 consensus proposal for the classification of hepatitis C virus (HCV) presented an agreed and uniform nomenclature for HCV variants and the criteria for their assignment into genotypes and subtypes. Since its publication, the available dataset of HCV sequences has vastly expanded through advancement in nucleotide sequencing technologies and an increasing focus on the role of HCV genetic variation in disease and treatment outcomes. The current study represents a major update to the previous consensus HCV classification, incorporating additional sequence information derived from over 1,300 (near-)complete genome sequences of HCV available on public databases in May 2013. Analysis resolved several nomenclature conflicts between genotype designations and using consensus criteria created a classification of HCV into seven confirmed genotypes and 67 subtypes. There are 21 additional complete coding region sequences of unassigned subtype. The study additionally describes the development of a Web resource hosted by the International Committee for Taxonomy of Viruses (ICTV) that maintains and regularly updates tables of reference isolates, accession numbers, and annotated alignments ( http://talk.ictvonline.org/links/hcv/hcv-classification.htm ). The Flaviviridae Study Group urges those who need to check or propose new genotypes or subtypes of HCV to contact the Study Group in advance of publication to avoid nomenclature conflicts appearing in the literature. While the criteria for assigning genotypes and subtypes remain unchanged from previous consensus proposals, changes are proposed in the assignment of provisional subtypes, subtype numbering beyond “w,” and the nomenclature of intergenotypic recombinant. Conclusion : This study represents an important reference point for the consensus classification of HCV variants that will be of value to researchers working in clinical and basic science fields.

International standardization and coordination of the nomenclature of variants of hepatitis C virus (HCV) is increasingly needed as more is discovered about the scale of HCV-related liver disease and important biological and antigenic differences that exist between variants. A group of scientists expert in the field of HCV genetic variability, and those involved in development of HCV sequence databases, the Hepatitis Virus Database (Japan), euHCVdb (France), and Los Alamos (United States), met to re-examine the status of HCV genotype nomenclature, resolve conflicting genotype or subtype names among described variants of HCV, and draw up revised criteria for the assignment of new genotypes as they are discovered in the future. A comprehensive listing of all currently classified variants of HCV incorporates a number of agreed genotype and subtype name reassignments to create consistency in nomenclature. The paper also contains consensus proposals for the classification of new variants into genotypes and subtypes, which recognizes and incorporates new knowledge of HCV genetic diversity and epidemiology. A proposal was made that HCV variants be classified into 6 genotypes (representing the 6 genetic groups defined by phylogenetic analysis). Subtype name assignment will be either confirmed or provisional, depending on the availability of complete or partial nucleotide sequence data, or remain unassigned where fewer than 3 examples of a new subtype have been described. In conclusion , these proposals provide the framework by which the HCV databases store and provide access to data on HCV, which will internationally coordinate the assignment of new genotypes and subtypes in the future. (Hepatology 2005.)

The Flaviviridae is a family of small enveloped viruses with RNA genomes of 9000–13 000 bases. Most infect mammals and birds. Many flaviviruses are host-specific and pathogenic, such as hepatitis C virus in the genus Hepacivirus. The majority of known members in the genus Flavivirus are arthropod borne, and many are important human and veterinary pathogens (e.g. yellow fever virus, dengue virus). This is a summary of the current International Committee on Taxonomy of Viruses (ICTV) report on the taxonomy of the Flaviviridae, which is available at www.ictv.global/report/flaviviridae.

Worldwide, HCV is a major etiologic agent of chronic hepatitis that may lead to the development of liver cirrhosis and hepatocellular carcinoma. Thus, significant morbidity and mortality is caused by HCV infection and effective control measures against the spread of this virus are needed. Originally, the extent of genetic heterogeneity of HCV was not fully appreciated. However, the breadth of the genetic heterogeneity of HCV is great, and this may have important implications in diagnosis, pathogenesis, treatment, and vaccine development. In an infected individual the HCV genome population circulates as a quasispecies distribution of closely related yet heterogeneous RNA sequences centered around one dominant sequence. The dominant sequence, as well as the consensus sequence, changes sequentially during the course of the infection. A hypervariable region (HVR1) within one of the envelope proteins of HCV (E2) evolves very rapidly. Patients infected with HCV mount a humoral immune response to epitopes of HVR1. However, sequential changes in the consensus sequence of HVR1 during infection result in the generation of variants that are not recognized by preexisting antibodies. This might represent a mechanism by which HCV evades host immune surveillance and establishes and maintains persistent infection. It will be important to determine whether HVR1 of HCV, as was found for the V3 loop of HIV, contains epitopes that elicit neutralizing antibodies against HCV. Furthermore, it will be important to determine whether the quasispecies nature of HCV helps the virus evade the cytotoxic T-cell response of the host. Analysis of complete or partial HCV genomic sequences revealed that HCV exists as multiple, distinct genotypes. A total of nine major genetic groups and at least 30 subgroups have been recognized. To evaluate the current classification of HCV genotypes, we performed phylogenetic analyses of complete and partial nucleotide sequences from isolates that represent all published variants of HCV. Analysis of complete HCV sequences, which represent three major genetic groups, supports the currently used genotype classification scheme. However, analysis of the partial genomic regions (ie, C, E1, and NS5b) of HCV isolates that represent all recognized variants of HCV demonstrates that the genetic relatedness among some of the genotypes was not equivalent in the different gene regions. Furthermore, the distinction among isolates, subtypes, and types of HCV was not always clear. This finding might reflect the shortcomings of analyzing only limited gene regions or may reflect the wide spectrum of genetic variation of HCV.(ABSTRACT TRUNCATED AT 400 WORDS)

We have examined the progression of hepatitis C virus (HCV) infections by gene expression analysis of liver biopsies in acutely infected chimpanzees that developed persistent infection, transient viral clearance, or sustained clearance. Both common responses and outcome-specific changes in expression were observed. All chimpanzees showed gene expression patterns consistent with an IFN-α response that correlated with the magnitude and duration of infection. Transient and sustained viral clearance were uniquely associated with induction of IFN-γ-induced genes and other genes involved in antigen processing and presentation and the adaptive immune response. During the early stages of infection, host genes involved in lipid metabolism were also differentially regulated. We also show that drugs that affect these biosynthetic pathways can regulate HCV replication in HCV replicon systems. Our results reveal genome-wide transcriptional changes that reflect the establishment, spread, and control of infection, and they reveal potentially unique antiviral programs associated with clearance of HCV infection.

To define the early events that determine the outcome of acute hepatitis C virus (HCV) infection, we compared the course of viremia with the peripheral and intrahepatic T cell response and intrahepatic cytokine profile in six acutely infected chimpanzees. Three different outcomes were observed after peak viral titers were reached: sustained viral clearance, transient viral clearance followed by chronic infection, and chronic infection that persisted at initial peak titers. The results indicate that HCV spread outpaces the T cell response and that HCV rapidly induces but is not controlled by IFN-α/β; that viral clearance follows the entry and accumulation of HCV-specific IFN-γ-producing T cells in the liver; and that it may not require the destruction of infected cells.