Frequent Recovery and Broad Genotype 2 Diversity Characterize Hepatitis C Virus Infection in Ghana, West Africa

Candotti, Daniel; Temple, Jillian; Sarkodie, Francis; Allain, Jean‐Pierre

doi:10.1128/jvi.77.14.7914-7923.2003

Cited by 134 publications

(145 citation statements)

References 52 publications

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“…Endemic strains belonging to genotypes 1 and 2 are found in West Africa (2,20,47,66). Similar regional patterns of endemic diversity have been found for genotype 3 in South Asia, for genotype 4 in Central Africa and the Middle East, and for genotype 6 in East Asia (28,32,36).…”

supporting

confidence: 54%

Genetic History of Hepatitis C Virus in East Asia

Pybus

Barnes

Taggart

et al. 2009

J Virol

196

213

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The hepatitis C virus (HCV), which currently infects an estimated 3% of people worldwide, has been present in some human populations for several centuries, notably HCV genotypes 1 and 2 in West Africa and genotype 6 in Southeast Asia. Here we use newly developed methods of sequence analysis to conduct the first comprehensive investigation of the epidemic and evolutionary history of HCV in Asia. Our analysis includes new HCV core (n ‫؍‬ 16) and NS5B (n ‫؍‬ 14) gene sequences, obtained from serum samples of jaundiced patients from Laos. These exceptionally diverse isolates were analyzed in conjunction with all available reference strains using phylogenetic and Bayesian coalescent methods. We performed statistical tests of phylogeographic structure and applied a recently developed "relaxed molecular clock" approach to HCV for the first time, which indicated an unexpectedly high degree of rate variation. Our results reveal a >1,000-year-long development of genotype 6 in Asia, characterized by substantial phylogeographic structure and two distinct phases of epidemic history, before and during the 20th century. We conclude that HCV lineages representing preexisting and spatially restricted strains were involved in multiple, independent local epidemics during the 20th century. Our analysis explains the generation and maintenance of HCV diversity in Asia and could provide a template for further investigations of HCV spread in other regions.

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supporting

confidence: 54%

Genetic History of Hepatitis C Virus in East Asia

Pybus

Barnes

Taggart

et al. 2009

J Virol

196

213

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“…Not all patients with occult HCV infection displayed specific CD4 ϩ T-cell responses. One possible explanation is the fact that all our patients with occult HCV infection had genotype 1b (2), which seems to induce T-cell responses less frequently than genotype 2 or 3 (1,11,14). The present study does not exclude the presence of additional T-cell reactivities not yet investigated, and thus a detailed comprehensive analysis is warranted.…”

Section: Discussionmentioning

confidence: 89%

Cellular Immune Responses Associated with Occult Hepatitis C Virus Infection of the Liver

Quiroga

Llorente

Castillo

et al. 2006

J Virol

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Occult hepatitis C virus (HCV) infection is a type of recently identified chronic infection that is evidenced only by detection of HCV RNA in liver; patients consistently test negative for antibodies to HCV and HCV RNA in serum. Using ex vivo and in vitro measures of T-cell responses, we have identified functional virus-specific memory CD4؉ and CD8 ؉ T cells in the peripheral blood of patients with occult HCV infection. The features of the virus-specific T cells were consistent with immune surveillance functions, supporting previous exposure to HCV. In addition, the magnitudes of CD4؉ and CD8 ؉ T-cell responses were in parallel and correlated inversely with the extent of liver HCV infection. The detection of HCV-specific T cells in individuals in whom HCV RNA can persist in the liver despite the absence of viremia and antibodies indicates that HCV replication is prolonged in the face of virus-specific CD4؉ and CD8 ؉ T-cell responses. These findings demonstrate that HCV-specific cellular immune responses are markers not only of previous exposure to and recovery from HCV but also of ongoing occult HCV infection.Current criteria for hepatitis C virus (HCV) infection include detection of specific antibodies by enzyme immunoassay and confirmation by immunoblot assay (40). Chronic HCV infection is established in approximately 50 to 80% of virusexposed individuals, with 170 million people being infected worldwide (30). Patients in whom HCV persists usually remain positive for anti-HCV and HCV RNA in serum unless HCV is cleared from the circulation either spontaneously or under antiviral treatment (30,41). Another type of chronic infection, occult HCV, has recently been identified in a group of patients who have abnormal liver function tests and histological damage (2). Occult HCV infection is characterized by the presence of HCV RNA in the liver in patients who consistently test negative for antibodies to HCV and HCV RNA in serum. Compared with chronic hepatitis C, occult HCV infection seems to be a less aggressive form of the disease caused by the hepatitis C virus (25). A recent report suggests that interferonbased therapy may have potential benefits in the treatment of patients with occult HCV infection (24).Virus-specific T-cell responses have been detected in the blood of HCV-seronegative healthy persons frequently exposed to HCV (16,36) and in patients lacking humoral responses who have presumably recovered from acute hepatitis C (41). HCV-specific cellular responses can be detected in patients receiving antiviral therapy in association with HCV RNA clearance from the blood (5,11,12). In spite of this, detectable HCV may persist in the liver in so-called sustained responders to treatment (27,29). Therefore, we questioned whether HCV-specific T-cell responses are detectable in patients with occult HCV infection.(This work was presented in part at the 55th Annual Meet- MATERIALS AND METHODSStudy subjects. Fifty patients with occult HCV infection were enrolled in this study. The selection criteria were having susta...

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“…After pelleting the magnetic beads, supernatants were transferred to new tubes and viral RNA extraction was continued as indicated by the manufacturer. HCV RNA was quantified by real-time PCR using a PE Applied Biosystems Prism model 7700 sequence detector (Applied Biosystems) as described previously (Hamaia et al, 2001) or using the Mx4000 Multiplex Quantitative PCR system (Stratagene) as described previously (Candotti et al, 2003). The C t value, which correlates inversely with the concentration of target RNA, was determined as the cycle number where the fluorescence emission of the reporter probe increased above a threshold level.…”

Section: Methodsmentioning

confidence: 99%

Hepatitis C virus interacts with human platelet glycoprotein VI

Zahn

Jennings

Ouwehand

et al. 2006

Journal of General Virology

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Hepatitis C virus (HCV) interacts with human platelets in vivo as a potential transport of infectious virions to the target liver. The binding of native viral particles with the platelet membrane glycoprotein VI (GPVI) was analysed. A consistent interaction between HCV from plasma or after purification by two different methods and the recombinant extracellular immunoglobulin (Ig)-like domains of human GPVI (hD1D2) was observed with two independent experimental approaches: pull-down and ELISA assays. Between 2 and 7 % of HCV particles were specifically bound to hD1D2. The binding was inhibited by an anti-hD1D2 in a dose-dependent manner. Human D1D2 interaction with HCV was significantly higher than the murine D1D2, supporting the specificity of the interaction and to the single human domains (D1 and D2), suggesting that both Ig-like domains of the molecule are required for efficient binding. GPVI may be a platelet surface ligand for HCV playing a role in viral transport and persistence. INTRODUCTIONHepatitis C virus (HCV) infection is a global health problem, being a major cause of cirrhosis and hepatocellular carcinoma worldwide. The infection can also lead to a number of serious extra-hepatic manifestations (Major et al., 2001) and the existence of extra-hepatic viral reservoirs, such as lymphocytes, as well as the importance that they might have in the pathophysiology of infection becoming increasingly recognized.HCV infection is also associated with thrombocytopenia. Several investigators have reported HCV association with platelets (de Almeida et al., 2004; Floreani et al., 1996;Li et al., 1994;Nagamine et al., 1996;Silva et al., 1992;Takehara et al., 1994). We have previously shown the interaction of immunoglobulin (Ig) G-free and IgG-complexed HCV with platelets in chronically infected patients (Hamaia et al., 2001). Viral interaction with platelets is well recognized, as it has been described for other viruses such as herpes simplex virus (Forghani & Schmidt, 1983), Vaccinia virus (Bik et al., 1982), Human immunodeficiency virus 1 (HIV-1) (Lee et al., 1998(Lee et al., , 1993Olinger et al., 2000), echovirus 1 (Xing et al., 2004), hantavirus (Gavrilovskaya et al., 1998) and the flavivirus dengue type 2 (Wang et al., 1995) among others. Several mechanisms have been proposed as contributing to thrombocytopenia, but recently a positive correlation between thrombocytopenia and HCV association with platelets was described (de Almeida et al., 2004), suggesting a direct viral effect on platelet count.Platelets do not express CD81 (Levy et al., 1998), SR-BI (Rhainds & Brissette, 2004), DC-and L-SIGN (van Kooyk & Geijtenbeek, 2003) or the classical LDL-R (Korporaal et al., 2004;Pedreno et al., 1992), which are putative HCV receptors (Agnello et al., 1999;Gardner et al., 2003;Lozach et al., 2003; Monazahian et al., 1999;Pileri et al., 1998;Pohlmann et al., 2003;Scarselli et al., 2002). Thus, other molecule(s) might mediate the interaction between HCV and platelets.Preliminary work in the laboratory identified a 6...

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Frequent Recovery and Broad Genotype 2 Diversity Characterize Hepatitis C Virus Infection in Ghana, West Africa

Cited by 134 publications

References 52 publications

Genetic History of Hepatitis C Virus in East Asia

Genetic History of Hepatitis C Virus in East Asia

Cellular Immune Responses Associated with Occult Hepatitis C Virus Infection of the Liver

Hepatitis C virus interacts with human platelet glycoprotein VI

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