Serological and molecular analysis of hepatitis C virus envelope regions 1 and 2 during acute and chronic infections in chimpanzees

Doorn, Leen–Jan van; Hoek, Kitty van; Martinoff, Guy de; Bosman, Fons; Stuyver, Lieven; Kos, Ton; Frantzen, Inge; Sillekens, Peter; Maertens, Geert; Quint, Wim

doi:10.1002/(sici)1096-9071(199708)52:4<441::aid-jmv17>3.0.co;2-j

Cited by 9 publications

(7 citation statements)

References 36 publications

(34 reference statements)

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“…Recombinant carboxy-terminal-truncated envelope glycoprotein E1 (comprising amino acid [aa] 192 to 326) and E2 (aa 384 to 673) were generated using recombinant vaccinia viruses containing HCV envelope cDNAs of European HCV 1b isolate (BE11) and purified as described previously (26,45). HCV-LPs were synthesized and purified from insect cells infected with recombinant baculoviruses containing the cDNA of the HCV structural proteins of HCV strain H77c (genotype 1a) as described recently (49).…”

Section: Methodsmentioning

confidence: 71%

Viral and Cellular Determinants of the Hepatitis C Virus Envelope-Heparan SulfateInteraction

Barth

Schnober

Zhang

et al. 2006

J Virol

162

125

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Hepatitis C virus (HCV) is a major cause of posttransfusion and community-acquired hepatitis in the world. The majority of HCV-infected individuals develop chronic hepatitis that may progress to liver cirrhosis and hepatocellular carcinoma (10). Treatment options are limited, and a vaccine to prevent HCV infection is not available (14).HCV has been classified in a separate genus (Hepacivirus) of the Flaviviridae family. The virion contains a positive-strand RNA genome of approximately 9,600 nucleotides. The genome encodes a single polyprotein of 3,010 to 3,030 amino acids that is co-and posttranslationally processed by host and viral proteases into structural and nonstructural proteins. The HCV structural proteins comprise the core protein and the two envelope glycoproteins E1 and E2 (23). HCV preferentially replicates in the cytoplasm of hepatocytes, but distinct HCV sequences have also been isolated from B cells and dendritic cells (1). Several experimental systems have suggested that virus binding and entry are mediated by envelope glycoprotein E2. Using recombinant envelope glycoproteins (35), HCV-like particles (HCV-LPs) (5), retroviral HCV pseudotype particles (HCVpp) (3), and recombinant infectious virions (22,48,54) as model systems for the first steps of viral infection, CD81 (35), scavenger receptor class B type I (SR-BI) (38), dendritic cell-specific intercellular adhesion molecule 3 grabbing-nonintegrin (DC-SIGN) (25), and the glycosaminoglycan heparan sulfate (HS) (2) have been identified as HCV receptor candidates.HS comprises a family of linear polysaccharides located at the surface of mammalian cells and in the extracellular matrix. HS varies with respect to composition and quantity among different species, cell types, tissues, and the stage of cellular development. HS consists mainly of repeating disaccharide units [GlcA-GlcNAc] n , where GlcA is glucuronic acid and GlcNAc is N-acetylglucosamine. However, these saccharides undergo N deacetylation and N sulfation of the GlcNAc residues, O sulfation at various positions, and epimerization of GlcA to iduronic acid (12). These secondary modifications give rise to an enormous structural diversity throughout the length of each chain. HS chains are attached to a core protein, forming a class of glycoproteins called proteoglycans. A number of studies have indicated the potential role of heparan sulfate proteoglycans (HSPGs) in the regulation of cell growth and transformation, differentiation processes, and cell adhesion. In hepatocytes, HSPGs are thought to bridge the extracellular matrix and the intracellular cytoskeleton (36).Microorganisms may take advantage of the widespread distribution of proteoglycans on cell surfaces by using them as ligands for their attachment to the target cell. For several viruses, including members of the Flaviviridae family such as dengue virus (9), classical swine fever (18), and tick-borne

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Section: Methodsmentioning

confidence: 71%

Viral and Cellular Determinants of the Hepatitis C Virus Envelope-Heparan SulfateInteraction

Barth

Schnober

Zhang

et al. 2006

J Virol

162

125

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“…HCV-LP E2 concentration was determined as described (18). Recombinant C-terminal-truncated envelope glycoprotein E2 (comprising amino acids 384 -673) and E2 containing a deletion of HVR1 (⌬E2; comprising amino acids 412-715) were generated using recombinant vaccinia viruses containing HCV envelope cDNAs of a European HCV 1b isolate (39). Recombinant NS5A and NS5B proteins (Mikrogen Corp., Martinsried, Germany) were generously provided by H. Diepolder, Dept.…”

Section: Methodsmentioning

confidence: 99%

Cellular Binding of Hepatitis C Virus Envelope Glycoprotein E2 Requires Cell Surface Heparan Sulfate

Barth

Schäfer

Adah

et al. 2003

Journal of Biological Chemistry

416

358

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“…3D). A poor humoral response to structural region proteins of HCV is typical for chimpanzees (3,8,44). The appearance of antibodies within 1 to 2 weeks after each rechallenge are indicative of anamnestic responses and were observed for all of the antigens tested ( Fig.…”

Section: Ihgi Of Infectious and Noninfectious Hcv Rna Protects A Chimmentioning

confidence: 99%

Intrahepatic Genetic Inoculation of Hepatitis C Virus RNA Confers Cross-Protective Immunity

Weiner¹,

Paliard²,

Selby³

et al. 2001

J Virol

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Naturally occurring hepatitis C virus (HCV) infection has long been thought to induce a weak immunity which is insufficient to protect an individual from subsequent infections and has cast doubt on the ability to develop effective vaccines. A series of intrahepatic genetic inoculations (IHGI) with type 1a HCV RNA were performed in a chimpanzee to determine whether a form of genetic immunization might stimulate protective immunity. We demonstrate that the chimpanzee not only developed protective immunity to the homologous type 1a RNA after rechallenge by IHGI but was also protected from chronic HCV infection after sequential rechallenge with 100 50% chimpanzee infectious doses of a heterologous type 1a (H77) and 1b (HC-J4) whole-virus inoculum. These results offer encouragement to pursue the development of HCV vaccines.

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Serological and molecular analysis of hepatitis C virus envelope regions 1 and 2 during acute and chronic infections in chimpanzees

Cited by 9 publications

References 36 publications

Viral and Cellular Determinants of the Hepatitis C Virus Envelope-Heparan SulfateInteraction

Viral and Cellular Determinants of the Hepatitis C Virus Envelope-Heparan SulfateInteraction

Cellular Binding of Hepatitis C Virus Envelope Glycoprotein E2 Requires Cell Surface Heparan Sulfate

Intrahepatic Genetic Inoculation of Hepatitis C Virus RNA Confers Cross-Protective Immunity

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