HEPATITIS C: An Overview

Bhandari, Maria; Wright, M

doi:10.1146/annurev.med.46.1.309

Cited by 21 publications

(5 citation statements)

References 40 publications

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“…The high concentration of lactoferrin in breast milk and the increased concentration of lactoferrin in plasma during pregnancy may explain the unexpectedly rare rate of vertical transmission of HCV compared to that of hepatitis B virus (1,17,25,27). The biological relevance of the interaction of lactoferrin and the HCV envelope proteins remains to be explored, since the liver is the target organ of HCV infection and is also the main clearance site of lactoferrin in the blood (20).…”

Section: Discussionmentioning

confidence: 99%

Hepatitis C virus envelope proteins bind lactoferrin

Kaneko

et al. 1997

J Virol

148

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Hepatitis C virus (HCV) has two envelope proteins, E1 and E2, which form a heterooligomer. During dissection of interacting regions of HCV E1 and E2, we found the presence of an interfering compound or compounds in skim milk. Here we report that human as well as bovine lactoferrin, a multifunctional immunomodulator, binds two HCV envelope proteins. As determined by far-Western blotting, the bacterially expressed E1 and E2 could bind lactoferrin in human milk directly separated or immunopurified and separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The bindings of lactoferrin and HCV envelope proteins in vitro were confirmed by another method, the pull-down assay, with immunoprecipitated lactoferrin-bound protein A resin. By the same assay, mammal-expressed recombinant E1 and E2 were also demonstrated to bind human lactoferrin efficiently in vitro. Direct interaction between E2 and lactoferrin was proved in vivo, since anti-human lactoferrin antibody efficiently coimmunoprecipitated with secreted and intracellular forms of the E2 protein, but not glutathione S-transferase (GST), from lysates of HepG2 cells transiently cotransfected with the expression plasmids of human lactoferrin and gE2t-GST (the N-terminal two-thirds of E2 fused to GST) or GST. The N-terminal loop of lactoferrin, the region important for the antibacterial activity, has only a little role in the binding ability to HCV E2 but affected the secretion or stability of lactoferrin. Taken together, these results indicate the specific interaction between lactoferrin and HCV envelope proteins in vivo and in vitro.

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Section: Discussionmentioning

confidence: 99%

Hepatitis C virus envelope proteins bind lactoferrin

Kaneko

et al. 1997

J Virol

148

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“…For example, both the hepatitis C virus (HCV) [40], [41] and the human immunodeficiency virus (HIV) [42], [43] establish persistent infections, and therefore pose major challenges to human health. Similarly, lymphocytic choriomeningitis virus (LCMV) can establish persistent infection in the mouse central nervous and immune systems [44], [45], and Sendai virus is also able to establish persistent infections in mouse respiratory tissues [46].…”

Section: Introductionmentioning

confidence: 99%

Negative Regulation of Interferon-β Gene Expression during Acute and Persistent Virus Infections

Maniatis

2011

PLoS ONE

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The production of type I interferons (IFNs) in response to viral infections is critical for antiviral immunity. However, IFN production is transient, and continued expression can lead to inflammatory or autoimmune diseases. Thus, understanding the mechanisms underlying the negative regulation of IFN expression could lead to the development of novel therapeutic approaches to the treatment of these diseases. We report that the transcription factor IRF3 plays a central role in the negative regulation of interferon-β (IFNβ) expression during both acute and persistent (chronic) virus infections. We show that the degradation of IRF3 during acute infections, rather than the activation of transcriptional repressors, leads to the down regulation of IFNβ expression. We also show that the block to IFNβ expression in mouse embryonic fibroblasts that are persistently infected with Sendai virus (SeV) correlates with the absence of transcriptionally active IRF3. Remarkably, ongoing protein synthesis and viral replication are required to maintain repression of the IFNβ gene in persistently infected cells, as the gene can be activated by the protein synthesis inhibitor cycloheximide, or by the antiviral drug ribavirin. Finally, we show that the SeV V protein inhibits IRF3 activity in persistently infected cells. Thus, in conjunction with the known interference with STAT1 by the SeV C protein, both IFN activation and its signaling pathways are blocked in persistently infected cells. We conclude that the transcription factor IRF3 is targeted for turnover and inactivation through distinct mechanisms from both the host cells and virus, leading to the inhibition of IFNβ gene expression during acute and persistent viral infections. These observations show that IRF3 plays a critical role, not only in the activation of the IFNβ gene, but also in the controlling the duration of its expression. (284 words)

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“…In comparison, HCV infection among blood donors or the general population is mostly low (1-2%) even in areas where HBV infection is endemic [Degos 1994;Bhandari and Wright, 1995;McCarthy et al, 1994;Ochi et al, 1991;Soni et al, 1993;Biltz et al, 1994]. This discrepancy between the high HBV and low HCV infection rates has been mainly attributed to a lack of introduction of HCV to the community.…”

Section: Introductionmentioning

confidence: 99%

High rate of hepatitis C virus infection in an isolated community: Persistent hyperendemicity or period-related phenomena?

Hsu

Yuh

et al. 1997

J. Med. Virol.

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We investigated underlying risks for hyperendemic hepatitis C virus (HCV) infection among the 1853 inhabitants of a mountainous village in Eastern Taiwan with high prevalence of HCV and hepatitis B virus (HBV). Among the 80 selected adults, we found that having resided away from the village before 1985 was protective against HCV infection, while residing in the village after 1985 posed little risk for HCV infection to children and young adults < 30 years of age. Among the 559 school children 7 through 14 years of age, anti-HCV prevalence was 1.9%, and the HBV carrier rate was 29%. Following up 270 children 1 year later, we found that new HCV infection occurred in 0.74% and new or repeated HBV infection occurred in 6.5% of the children, indicating distinct transmission patterns between HBV and HCV. Children of anti-HCV-positive mothers were either anti-HCV-negative or were infected by distinct genotypes of HCV from those infecting their mothers; most married couples in whom both were infected, were infected by HCV of discordant genotypes, indicating negligible importance of sexual or vertical HCV transmission. A case-control study comparing 13 anti-HCV-positive and 53 anti-HCV-negative children showed that having received parenteral medication in local clinics was a significant risk for HCV infection. Our data indicate that, unlike the case of HBV, HCV transmission by vertical or sexual route, or through casual contact are extremely inefficient, and our data further suggest that HCV hyperendemicity is unlikely to persist as a result of the more stringent practice of parenteral precautions in nearly all aspects of daily life.

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HEPATITIS C: An Overview

Cited by 21 publications

References 40 publications

Hepatitis C virus envelope proteins bind lactoferrin

Hepatitis C virus envelope proteins bind lactoferrin

Negative Regulation of Interferon-β Gene Expression during Acute and Persistent Virus Infections

High rate of hepatitis C virus infection in an isolated community: Persistent hyperendemicity or period-related phenomena?

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