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;42:962-973.)

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Human and simian immunodeficiency viruses (HIV and SIV), influenza virus, and hepatitis C virus (HCV) have heavily glycosylated, highly variable surface proteins. Here we explore N-linked glycosylation site (sequon) variation at the population level in these viruses, using a new Web-based program developed to facilitate the sequon tracking and to define patterns (www.hiv.lanl.gov). This tool allowed rapid visualization of the two distinctive patterns of sequon variation found in HIV-1, HIV-2, and SIV CPZ. The first pattern (fixed) describes readily aligned sites that are either simply present or absent. These sites tend to be occupied by high-mannose glycans. The second pattern (shifting) refers to sites embedded in regions of extreme local length variation and is characterized by shifts in terms of the relative position and local density of sequons; these sites tend to be populated by complex carbohydrates. HIV, with its extreme variation in number and precise location of sequons, does not have a net increase in the number of sites over time at the population level. Primate lentiviral lineages have host species-dependent levels of sequon shifting, with HIV-1 in humans the most extreme. HCV E1 and E2 proteins, despite evolving extremely rapidly through point mutation, show limited sequon variation, although two shifting sites were identified. Human influenza A hemagglutinin H3 HA1 is accumulating sequons over time, but this trend is not evident in any other avian or human influenza A serotypes.

Although parasite-host co-speciation is a long-held hypothesis, convincing evidence for long-term co-speciation remains elusive, largely because of small numbers of hosts and parasites studied and uncertainty over rates of evolutionary change. Co-speciation is especially rare in RNA viruses, in which cross-species transfer is the dominant mode of evolution. Simian foamy viruses (SFVs) are ubiquitous, non-pathogenic retroviruses that infect all primates. Here we test the co-speciation hypothesis in SFVs and their primate hosts by comparing the phylogenies of SFV polymerase and mitochondrial cytochrome oxidase subunit II from African and Asian monkeys and apes. The phylogenetic trees were remarkably congruent in both branching order and divergence times, strongly supporting co-speciation. Molecular clock calibrations revealed an extremely low rate of SFV evolution, 1.7 x 10(-8) substitutions per site per year, making it the slowest-evolving RNA virus documented so far. These results indicate that SFVs might have co-speciated with Old World primates for at least 30 million years, making them the oldest known vertebrate RNA viruses.

The hepatitis C virus (HCV) is a significant public health threat worldwide. The virus is highly variable and evolves rapidly, making it an elusive target for the immune system and for vaccine and drug design. Presently, ∼50 000 HCV sequences have been published. A central website that provides annotated sequences and analysis tools will be helpful to HCV scientists worldwide. The HCV sequence database collects and annotates sequence data, and provides them to the public via a website that contains a user-friendly search interface and a large number of sequence analysis tools, following the model of the highly regarded and widely used Los Alamos HIV database. The HCV website can be accessed via http://hcv.lanl.gov and http://hcv-db.org.