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Jens Bukh

Bio: Jens Bukh is an academic researcher from University of Copenhagen. The author has contributed to research in topics: Hepatitis C virus & Virus. The author has an hindex of 71, co-authored 270 publications receiving 21051 citations. Previous affiliations of Jens Bukh include Copenhagen University Hospital & Hvidovre Hospital.


Papers
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Journal ArticleDOI
TL;DR: This 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.

1,219 citations

Journal ArticleDOI
TL;DR: Gene expression analysis of liver biopsies in acutely infected chimpanzees reveals 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.
Abstract: Previous studies in hepatitis B virus (HBV)-infected humans and chimpanzees suggest that control of HBV infection involves the cells, effector functions, and molecular mediators of the immune response. The objective of the current study was to identify, in the liver of acutely HBV-infected chimpanzees, the spectrum of virus-induced and immune response-related genes that regulate the infection. The results demonstrate that HBV does not induce any genes during entry and expansion, suggesting it is a stealth virus early in the infection. In contrast, a large number of T cell-derived IFN-γ-regulated genes are induced in the liver during viral clearance, reflecting the impact of an adaptive T cell response that inhibits viral replication and kills infected cells, thereby terminating the infection.

1,173 citations

Journal ArticleDOI
TL;DR: It is revealed that HCV exists as multiple, distinct genotypes, and phylogenetic analyses of complete and partial nucleotide sequences from isolates that represent all published variants of HCV revealed that the genetic relatedness among some of the genotypes was not equivalent in the different gene regions.
Abstract: 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)

867 citations

Journal ArticleDOI
TL;DR: The results indicate that HCV spread outpaces the T cell response and thatHCV 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.
Abstract: 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.

657 citations


Cited by
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Journal ArticleDOI
TL;DR: It is established that the mitochondrial gene cytochrome c oxidase I (COI) can serve as the core of a global bioidentification system for animals and will provide a reliable, cost–effective and accessible solution to the current problem of species identification.
Abstract: Although much biological research depends upon species diagnoses, taxonomic expertise is collapsing. We are convinced that the sole prospect for a sustainable identification capability lies in the construction of systems that employ DNA sequences as taxon 'barcodes'. We establish that the mitochondrial gene cytochrome c oxidase I (COI) can serve as the core of a global bioidentification system for animals. First, we demonstrate that COI profiles, derived from the low-density sampling of higher taxonomic categories, ordinarily assign newly analysed taxa to the appropriate phylum or order. Second, we demonstrate that species-level assignments can be obtained by creating comprehensive COI profiles. A model COI profile, based upon the analysis of a single individual from each of 200 closely allied species of lepidopterans, was 100% successful in correctly identifying subsequent specimens. When fully developed, a COI identification system will provide a reliable, cost-effective and accessible solution to the current problem of species identification. Its assembly will also generate important new insights into the diversification of life and the rules of molecular evolution.

9,879 citations

Journal ArticleDOI
TL;DR: In patients with chronic hepatitis C, initial therapy withinterferon and ribavirin was more effective than treatment with interferon alone.
Abstract: Background Only 15 to 20 percent of patients with chronic hepatitis C have a sustained virologic response to interferon therapy. We compared the efficacy and safety of recombinant interferon alfa-2b alone with those of a combination of interferon alfa-2b and ribavirin for the initial treatment of patients with chronic hepatitis C. Methods We randomly assigned 912 patients with chronic hepatitis C to receive standard-dose interferon alfa-2b alone or in combination with ribavirin (1000 or 1200 mg orally per day, depending on body weight) for 24 or 48 weeks. Efficacy was assessed by measurements of serum hepatitis C virus (HCV) RNA and serum aminotransferases and by liver biopsy. Results The rate of sustained virologic response (defined as an undetectable serum HCV RNA level 24 weeks after treatment was completed) was higher among patients who received combination therapy for either 24 weeks (70 of 228 patients, 31 percent) or 48 weeks (87 of 228 patients, 38 percent) than among patients who received interfe...

3,531 citations

Journal ArticleDOI
TL;DR: This document has been approved by the AASLD, the Infectious Diseases Society of America, and the American College of Gastroenterology.

3,013 citations

Journal ArticleDOI
02 Jul 1999-Science
TL;DR: This work defines the structure of HCV replicons functional in cell culture and provides the basis for a long-sought cellular system that should allow detailed molecular studies ofHCV and the development of antiviral drugs.
Abstract: An estimated 170 million persons worldwide are infected with hepatitis C virus (HCV), a major cause of chronic liver disease. Despite increasing knowledge of genome structure and individual viral proteins, studies on virus replication and pathogenesis have been hampered by the lack of reliable and efficient cell culture systems. A full-length consensus genome was cloned from viral RNA isolated from an infected human liver and used to construct subgenomic selectable replicons. Upon transfection into a human hepatoma cell line, these RNAs were found to replicate to high levels, permitting metabolic radiolabeling of viral RNA and proteins. This work defines the structure of HCV replicons functional in cell culture and provides the basis for a long-sought cellular system that should allow detailed molecular studies of HCV and the development of antiviral drugs.

2,982 citations

Journal ArticleDOI
TL;DR: The institution of blood-screening measures in developed countries has decreased the risk of transfusion-associated hepatitis to a negligible level, but new cases continue to occur mainly as a result of injection-drug use and, to a lesser degree, through other means of percutaneous or mucous-membrane exposure.
Abstract: Hepatitis C virus (HCV) infects an estimated 170 million persons worldwide and thus represents a viral pandemic, one that is five times as widespread as infection with the human immunodeficiency virus type 1 (HIV-1). The institution of blood-screening measures in developed countries has decreased the risk of transfusion-associated hepatitis to a negligible level, but new cases continue to occur mainly as a result of injection-drug use and, to a lesser degree, through other means of percutaneous or mucous-membrane exposure. Progression to chronic disease occurs in the majority of HCV-infected persons, and infection with the virus has become the main indication . . .

2,966 citations