Identification of glycosaminoglycan‐binding sites within hepatitis C virus envelope glycoprotein E2*

Olenina, Ludmila V.; Kuzmina, T. I.; Sobolev, Boris N.; Kuraeva, T. E.; Колесанова, Е. Ф.; Арчаков, А И

doi:10.1111/j.1365-2893.2005.00647.x

Cited by 21 publications

(15 citation statements)

References 58 publications

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“…, present in all Lospins (not shown). These patterns showed similarity to glycosaminoglycan (GAG) binding sites; XBnXmB (where X and B=non-basic and basic residues respectively, n=1, 2, or 3 basic residues and m=1 or 2 non-basic residues (Munoz and Linhardt, 2004;Olenina et al, 2005 , which are important in heparin binding (Olson et al, 2002;Schedin-Weiss et al, 2004;dela Cruz, 2006). To further examine the possibility of the basic residues on ␣-helix D of L5 and L13-16 being involved in heparin (GAG) binding activity, we calculated surface electrostatic potentials for L5 and L13-16 models.…”

Section: The Journal Of Experimental Biologymentioning

confidence: 99%

Molecular and expression analysis of a family of the Amblyomma americanum tick Lospins

Mulenga

Khumthong

Blandon

2007

Journal of Experimental Biology

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VRDKTRGKI166 in all Lospins, which are similar to consensus glycosaminoglycan (GAG) binding sites (XBnXmBX, where X and B are non-basic and basic residues, n=1 or 2 and m=1, 2 or 3). On three-dimensional models, the two putative GAG binding sites mapped onto ␣-helices D and F, respectively, with calculation of electrostatic surface potentials revealing basic patches on L5 and L13-16 models that are comparable to the heparinbinding site on antithrombin. RT-PCR expression analysis of 15 selected genes showed that the majority (11/15) of the Lospins were ubiquitously expressed in the midgut, ovary and salivary glands. On a neighbor-joining phylogeny guide tree, 15 serpins from other ticks and 17 Lospins from this study, a total of 32 tick serpin sequences, segregated into five groups with Lospins in groups A and D being conserved across tick species. The discovery of Lospins in this study sets the framework for future studies to understand the role of serpins in tick physiology.

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Section: The Journal Of Experimental Biologymentioning

confidence: 99%

Molecular and expression analysis of a family of the Amblyomma americanum tick Lospins

Mulenga

Khumthong

Blandon

2007

Journal of Experimental Biology

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“…Further studies suggested that the hypervariable region 1 (HVR1) of E2 binds with heparin, and the infectivity of the VSV/HCV pseudotype is diminished in the presence of soluble GAGs or decreased after the enzymatic removal of heparinlike GAGs from the cell surface (7). A different group of investigators have suggested that HCV particles can be efficiently purified from patient sera by using heparin, and GAG binding sites are located within E2 (27,32).…”

mentioning

confidence: 99%

Sulfated Homologues of Heparin Inhibit Hepatitis C Virus Entry into Mammalian Cells

Basu¹,

Kanda²,

Beyene³

et al. 2007

J Virol

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The mechanism of entry of hepatitis C virus (HCV) through interactions between the envelope glycoproteins and specific cell surface receptors remains unclear at this time. We have previously shown with the vesicular stomatitis virus (VSV)/HCV pseudotype model that the hypervariable region 1 of the HCV E2 envelope glycoprotein helps in binding with glycosaminoglycans present on the cell surface. In this study, we have examined the binding of HCV envelope glycoproteins with chemically modified derivatives of heparin. Furthermore, we have determined the functional relevance of the interaction of heparin derivatives with HCV envelope glycoproteins for infectivity by using a human immunodeficiency virus (HIV)/HCV pseudotype, a VSV/HCV pseudotype, and cell culture-grown HCV genotype 1a. Taken together, our results suggest that the HCV envelope glycoproteins rely upon O-sulfated esters of a heparin homologue to facilitate entry into mammalian cells.We first reported the generation of a vesicular stomatitis virus (VSV)/hepatitis C virus (HCV) pseudotype to understand the role of the ectodomains of HCV envelope glycoproteins in relation to the initiation of virus infection (20). Since VSV particles assemble at the plasma membrane (1), we expressed chimeric HCV envelope glycoproteins (E1G and E2G) by appending the transmembrane domain and cytoplasmic tail of VSV glycoprotein at their C termini to provide membrane anchor signals. This modification allowed for the localization of the glycoproteins to the cell surface for efficient incorporation onto VSV pseudotype particles. Pseudotypes generated from either E1G or E2G which had been expressed individually displayed a low level of infectivity, while the presence of both envelope glycoproteins significantly increased the infectious titer of the pseudotype (26). Interestingly, each HCV envelope protein is suggested to have class I and/or class II fusion peptide motifs (10,11,12,31), which may contribute to the infectivity of the parent virus. Murine leukemia virus (MuLV)-and human immunodeficiency virus (HIV)-derived pseudotypes were subsequently generated from human embryonic kidney epithelial cells (293T) by the expression of an unmodified HCV envelope genomic region (5, 15). Although there are apparent differences, the overall observations from MuLV-and HIV-derived pseudotypes were similar to observations from the VSV/HCV pseudotype (8, 26). We have previously observed that the E2 glycoprotein binds to cell surface glycosaminoglycans (GAGs) (7,24). Further studies suggested that the hypervariable region 1 (HVR1) of E2 binds with heparin, and the infectivity of the VSV/HCV pseudotype is diminished in the presence of soluble GAGs or decreased after the enzymatic removal of heparinlike GAGs from the cell surface (7). A different group of investigators have suggested that HCV particles can be efficiently purified from patient sera by using heparin, and GAG binding sites are located within E2 (27, 32).The binding of E2 with a heparin-like molecule appears to facilitate VSV-deri...

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“…Results of genome sequence analysis are applied in the studies directed to the development of vaccines against viral (Hepatitis C [71,72], SARS [9][10][11][12]) and bacterial (Tuberculosis [73,74], Syphilis [75], Meningitis [66]) infections. Moreover, genomics studies enable to design experimental vaccines against parasite infections (Malaria [76,77], Chlamydiosis [78,79]), which have been out of vaccine studies for a long time.…”

Section: Prediction Of the Functional Features Of Proteins Based On Tmentioning

confidence: 99%

Computer Design of Vaccines: Approaches, Software Tools and Informational Resources

Sobolev¹,

Olenina²,

Колесанова³

et al. 2005

CAD

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Development of computer methods in molecular biology and fast growth of microbial genomics data enabled new approach based on selecting in silico antigenic components to design vaccine constructs. It is expected that application of this technology will eliminate side effects of new vaccines and reduce the time consumption and financial expenses. The bioinformatics methods of sequence analysis are used to reveal the most prospective proteins or protein fragments of infectious agents as candidates for vaccine design. In these studies the specialized molecular immunology databases are widely used. The new approach ("Reverse vaccinology") could help in designing vaccines against diseases where traditional methods are not successful, e.g. when the viral genome reveals the extreme variability and permanent changes of antigenic properties that make difficulties for selection of molecular targets for medicines and candidate vaccines. A number of informational resources are already designed to collect and provide genomic data on certain microbes or viruses. The peculiarity of such resources is presentation of data, characterizing the different genomic variants of the same infectious agents. These structural data coupled with information on functional/immune features and software tools have to compose basis for constructing a new generation of vaccines against "common" and new infections such as AIDS, Hepatitis C, and SARS. The approaches published in literature, as well as the authors' original results are discussed.

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Identification of glycosaminoglycan‐binding sites within hepatitis C virus envelope glycoprotein E2*

Cited by 21 publications

References 58 publications

Molecular and expression analysis of a family of the Amblyomma americanum tick Lospins

Molecular and expression analysis of a family of the Amblyomma americanum tick Lospins

Sulfated Homologues of Heparin Inhibit Hepatitis C Virus Entry into Mammalian Cells

Computer Design of Vaccines: Approaches, Software Tools and Informational Resources

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