Antibody-free virion titer greatly differs between hepatitis C virus genotypes

Kimura, Yasumi; Hayashida, Kazuhiro; Ishibashi, Hiromi; Niho, Yoshiyuki; Yanagi, Yusuke

doi:10.1002/(sici)1096-9071(200005)61:1<37::aid-jmv6>3.0.co;2-e

Cited by 4 publications

(3 citation statements)

References 42 publications

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“…This conclusion is strengthened by two observations: (i) types 4 and 6 can spread quickly if they enter efficient contact networks (36)(37)(38)(39) and (ii) in the absence of such networks, HCV type 1 in West Africa shows evidence of long-term endemic infection (7). However, the possibility of viral genetic variability in infectiousness among subtypes should not yet be discounted entirely (40). Extrapolating our estimates into the near future, it is clear that, in terms of new infections, subtype 1a poses the greatest threat to public health.…”

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confidence: 92%

The Epidemic Behavior of the Hepatitis C Virus

Pybus

Charleston

Gupta

et al. 2001

Science

409

359

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Hepatitis C virus (HCV) is a leading worldwide cause of liver disease. Here, we use a new model of HCV spread to investigate the epidemic behavior of the virus and to estimate its basic reproductive number from gene sequence data. We find significant differences in epidemic behavior among HCV subtypes and suggest that these differences are largely the result of subtype-specific transmission patterns. Our model builds a bridge between the disciplines of population genetics and mathematical epidemiology by using pathogen gene sequences to infer the population dynamic history of an infectious disease.An estimated 170 million people worldwide are at risk of liver cirrhosis and liver cancer due to chronic infection with HCV (1). The virus is responsible for 10,000 deaths per year in the United States, and this rate is expected to increase substantially in the next two decades (2). HCV is a rapidly evolving single-stranded positivesense RNA virus that exhibits enormous genetic diversity. It is classified into six types (labeled 1 through 6) and numerous subtypes (labeled 1a, 1b, etc.), which differ in diversity, geographical distribution, and transmission route (3). Subtypes appear to differ in treatment response, although their role in variation of disease progression is unclear (2, 4 ). Any successful HCV vaccination or control strategy, therefore, requires an understanding of the nature and variability of epidemic behavior among subtypes.HCV was first isolated in 1989, and knowledge of its long-term epidemiology before that date is limited. Highly divergent strains have been found in restricted geographic areas such as West Africa and Southeast Asia, suggesting a long period of infection in these regions. In contrast, several globally prevalent subtypes are much less divergent, indicating a recent worldwide spread of these strains (5-7).We investigate HCV epidemiology using coalescent theory, a population genetic model that describes how the demographic history of a population determines the ancestral relationships of individuals sampled from it (8, 9). Phylogenies reconstructed from contemporary HCV gene sequences contain information about past population dynamics and can, therefore, be used to infer viral epidemic behavior (10). We also demonstrate one way in which the fundamental epidemiological quantity R 0 (the basic reproductive number of a pathogen) can be estimated from gene sequences. R 0 represents the average number of secondary infections generated by one primary case in a susceptible population and can be used to estimate the level of immunization or behavioral change required to control an epidemic (11).The framework of coalescent theory allows us to estimate N(t), a continuous function that represents the effective number of infections at time t. Time t is zero at the present and increases into the past, hence N(0) is the effective number of infections at the present. N(t) can be considered as the inbreeding effective population size of the viral epidemic (12). Previous viral coalescent studies have ...

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confidence: 92%

The Epidemic Behavior of the Hepatitis C Virus

Pybus

Charleston

Gupta

et al. 2001

Science

409

359

View full text Add to dashboard Cite

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“…Crucially, for HCV in Egypt it was possible to validate the genetic analysis against compelling epidemiological evidence (Frank et al, 2000). In addition to its epidemiological importance, HCV genetic diversity is of clinical relevance, as HCV genotypes vary in their susceptibility to treatment with ribavirin plus interferon (Yoshioka et al, 1992;Chemello et al, 1994;Zein, 2000) and in the effectiveness of the immune response that they elicit (Kimura et al, 2000). Furthermore, the enormous genetic diversity of HCV is a major obstacle to designing universally and sustainably efficacious vaccines.…”

Section: Introductionmentioning

confidence: 99%

Phylogeography and molecular epidemiology of hepatitis C virus genotype 2 in Africa

Markov

Pépin

Frost

et al. 2009

Journal of General Virology

102

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Understanding the origin and nature of hepatitis C virus (HCV) genetic diversity is critical for improving treatment and vaccine design, and such diversity is the sole source of information about the virus' epidemic history prior to its identification 20 years ago. In this paper, we study the molecular epidemiology of HCV genotype 2 in its region of endemic origin, west and central Africa. Our analysis includes 56 new and highly diverse HCV isolates sampled from infected individuals in Guinea-Bissau. By combining phylogenetic, geographical and epidemiological information, we find a previously unappreciated geographical structure in the diversity of HCV genotype 2, pointing to a history of eastwards spatial spread from the west African coast to Cameroon that took place over several centuries. Molecular clock analysis dates the common ancestor of HCV in Guinea-Bissau to 1470 (1414-1582). The phylogenetic position of isolates from Madagascar and Martinique suggests a role for the historical slave trade in the global dissemination of HCV and of the epidemic subtypes 2a and 2c. Coalescent-based estimates of epidemic growth indicate a rapid 20th-century spread of HCV genotype 2 in Cameroon that is absent in Guinea-Bissau. We discuss this contrast in the context of possible parenteral HCV exposure during public-health campaigns undertaken during the colonial era.

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“…HCV variation could occur throughout the genome; indeed, the putative viral envelope glycoprotein gene shows unusually high degrees of amino acid variation. The envelope glycoprotein gene, especially HVR1, is a potential prime target for host humoral immunity [Mondelli et al, 1999] and contains neutralizing antigenic epitopes [Shang et al, 1999] that are clone-specific [Zhou et al, 1999;Kimura et al, 2000]. Research has showed that anti-E2 correlates with self-limited and chronic infection of HCV [Prince et al, 1999].…”

Section: Introductionmentioning

confidence: 99%

Variant analysis and immunogenicity prediction of envelope gene of HCV strains from China

Cai

Zhang

Tian

et al. 2002

Journal of Medical Virology

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The putative envelope protein E2 of hepatitis C virus (HCV) is the most variable antigenic fragment in the whole viral genome and is responsible mainly for the large inter- and intra-individual heterogeneity of the infecting virus. To analyze variation and immunogenicity of HCV envelope genes of HCV strains from China, the serum samples from 12 Chinese patients with chronic hepatitis C from 10 cities of China were amplified, sequenced directly, and compared with international strains reported previously. Variant analysis and immunogenicity prediction were then carried out with computer programs. The results suggested that HCV envelope genes show diversity in the north and the south of China and that they vary among different genotypes. Therefore, the diversity among different genotypes and derived areas should be calculated for HCV vaccine design; simultaneously, domains characterized by the hydrophilicity and the conserved immunogenicity could be targeted, for example, the domain of aa434-444, aa408-414, aa449-462 in the envelope region and aa399-406 in HVR1. These data may hold the key for future development of HCV vaccine in China.

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Antibody-free virion titer greatly differs between hepatitis C virus genotypes

Cited by 4 publications

References 42 publications

The Epidemic Behavior of the Hepatitis C Virus

The Epidemic Behavior of the Hepatitis C Virus

Phylogeography and molecular epidemiology of hepatitis C virus genotype 2 in Africa

Variant analysis and immunogenicity prediction of envelope gene of HCV strains from China

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