Lipoprotein Lipase Inhibits Hepatitis C Virus (HCV) Infection by Blocking Virus Cell Entry
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Mendeley | Further Information

{"title"=>"Lipoprotein lipase inhibits hepatitis C virus (HCV) infection by blocking virus cell entry", "type"=>"journal", "authors"=>[{"first_name"=>"Patrick", "last_name"=>"Maillard", "scopus_author_id"=>"7005473058"}, {"first_name"=>"Marine", "last_name"=>"Walic", "scopus_author_id"=>"16433082500"}, {"first_name"=>"Philip", "last_name"=>"Meuleman", "scopus_author_id"=>"6506634527"}, {"first_name"=>"Farzin", "last_name"=>"Roohvand", "scopus_author_id"=>"12789521500"}, {"first_name"=>"Thierry", "last_name"=>"Huby", "scopus_author_id"=>"6602180714"}, {"first_name"=>"Wilfried", "last_name"=>"Goff", "scopus_author_id"=>"19034218300"}, {"first_name"=>"Geert", "last_name"=>"Leroux-Roels", "scopus_author_id"=>"19735190700"}, {"first_name"=>"Eve Isabelle", "last_name"=>"Pécheur", "scopus_author_id"=>"6602526371"}, {"first_name"=>"Agata", "last_name"=>"Budkowska", "scopus_author_id"=>"7004832928"}], "year"=>2011, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-80054837223", "pui"=>"362791004", "doi"=>"10.1371/journal.pone.0026637", "sgr"=>"80054837223", "pmid"=>"22039521"}, "id"=>"40858ab4-33de-3098-9b35-49457d8b3fc3", "abstract"=>"A distinctive feature of HCV is that its life cycle depends on lipoprotein metabolism. Viral morphogenesis and secretion follow the very low-density lipoprotein (VLDL) biogenesis pathway and, consequently, infectious HCV in the serum is associated with triglyceride-rich lipoproteins (TRL). Lipoprotein lipase (LPL) hydrolyzes TRL within chylomicrons and VLDL but, independently of its catalytic activity, it has a bridging activity, mediating the hepatic uptake of chylomicrons and VLDL remnants. We previously showed that exogenously added LPL increases HCV binding to hepatoma cells by acting as a bridge between virus-associated lipoproteins and cell surface heparan sulfate, while simultaneously decreasing infection levels. We show here that LPL efficiently inhibits cell infection with two HCV strains produced in hepatoma cells or in primary human hepatocytes transplanted into uPA-SCID mice with fully functional human ApoB-lipoprotein profiles. Viruses produced in vitro or in vivo were separated on iodixanol gradients into low and higher density populations, and the infection of Huh 7.5 cells by both virus populations was inhibited by LPL. The effect of LPL depended on its enzymatic activity. However, the lipase inhibitor tetrahydrolipstatin restored only a minor part of HCV infectivity, suggesting an important role of the LPL bridging function in the inhibition of infection. We followed HCV cell entry by immunoelectron microscopy with anti-envelope and anti-core antibodies. These analyses demonstrated the internalization of virus particles into hepatoma cells and their presence in intracellular vesicles and associated with lipid droplets. In the presence of LPL, HCV was retained at the cell surface. We conclude that LPL efficiently inhibits HCV infection by acting on TRL associated with HCV particles through mechanisms involving its lipolytic function, but mostly its bridging function. These mechanisms lead to immobilization of the virus at the cell surface. HCV-associated lipoproteins may therefore be a promising target for the development of new therapeutic approaches.", "link"=>"http://www.mendeley.com/research/lipoprotein-lipase-inhibits-hepatitis-c-virus-hcv-infection-blocking-virus-cell-entry-1", "reader_count"=>25, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>2, "Researcher"=>8, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>1, "Student > Master"=>5, "Other"=>1, "Student > Bachelor"=>1, "Lecturer"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>2, "Researcher"=>8, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>1, "Student > Master"=>5, "Other"=>1, "Student > Bachelor"=>1, "Lecturer"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>3, "Agricultural and Biological Sciences"=>12, "Medicine and Dentistry"=>7, "Physics and Astronomy"=>1, "Chemistry"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>7}, "Chemistry"=>{"Chemistry"=>1}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>12}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/721679"], "description"=>"<p>The viral preparation (JFH-1) was concentrated by centrifugation through a sucrose cushion and incubated with Huh7.5 cells at 4°C (T0), before transfer to 37°C and incubation for a further 5 (T5), 10 (T10), 15 (T15) or 20 (T20) min. Cells collected at all these time points were washed, fixed and stained with monoclonal antibodies, followed by secondary, colloidal gold-labeled anti-mouse IgG (see <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0026637#s2\" target=\"_blank\">Materials and Methods</a> section for details). T0 and T5, immunogold labeling of HCV E2 envelope glycoprotein with monoclonal AP-33 antibody; T10 and T20, immunogold labeling of HCV core protein with monoclonal ACAP-27 antibody. Asterisks indicate the presence of one silver-enhanced gold particle. ER, endoplasmic reticulum; LD, lipid droplet; M, mitochondrion; Nu, nucleus.</p>", "links"=>[], "tags"=>["microscopy", "cells", "hcv"], "article_id"=>392027, "categories"=>["Virology", "Biochemistry", "Infectious Diseases"], "users"=>["Patrick Maillard", "Marine Walic", "Philip Meuleman", "Farzin Roohvand", "Thierry Huby", "Wilfried Le Goff", "Geert Leroux-Roels", "Eve-Isabelle Pécheur", "Agata Budkowska"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0026637.g007", "stats"=>{"downloads"=>1, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Immunoelectron_microscopy_of_the_infection_of_Huh_7_5_cells_with_HCV_in_the_absence_of_LPL_/392027", "title"=>"Immunoelectron microscopy of the infection of Huh 7.5 cells with HCV in the absence of LPL.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-10-21 00:33:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/720925"], "description"=>"<p>The HCVcc strains JFH-1 (A) and J6/JFH-1 (B) were produced in the Huh7.5 hepatoma cell line. Cells were incubated with (or without) LPL for 30 min at 4°C and then with virus preparations for 2 h at 37°C to allow infection. RNA was extracted from cells 24 h post infection and HCV RNA was quantified by RT-qPCR. The data obtained were normalized with respect to levels of GADPH. The mJFH-1 (A) and mJ6/JFH-1 (B) correspond to HCVcc strains produced in chimeric uPA-SCID mice into which we transplanted human hepatocytes. Serum samples collected from infected mice were pooled and their capacity to infect Huh7.5 cells was assessed in the presence and absence of LPL, as outlined above. Cells infected in the absence (black bar) and in the presence of LPL (gray bar). The data are expressed as the amount of HCV RNA detected in cells infected in the presence of LPL as compared with the amount of HCV RNA in cells infected in the absence of LPL, expressed as a percentage.</p>", "links"=>[], "tags"=>["inhibits", "jfh-1", "strains", "produced", "chimeric", "upa-scid"], "article_id"=>391271, "categories"=>["Virology", "Biochemistry", "Infectious Diseases"], "users"=>["Patrick Maillard", "Marine Walic", "Philip Meuleman", "Farzin Roohvand", "Thierry Huby", "Wilfried Le Goff", "Geert Leroux-Roels", "Eve-Isabelle Pécheur", "Agata Budkowska"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0026637.g001", "stats"=>{"downloads"=>1, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_LPL_inhibits_cell_infection_by_the_JFH_1_and_J6_JFH_1_strains_produced_in_vitro_and_in_vivo_in_a_chimeric_uPA_SCID_mouse_model_/391271", "title"=>"LPL inhibits cell infection by the JFH-1 and J6/JFH-1 strains produced <i>in vitro</i> and <i>in vivo</i> in a chimeric uPA-SCID mouse model.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-10-21 00:21:11"}
  • {"files"=>["https://ndownloader.figshare.com/files/364925"], "description"=>"<div><p>A distinctive feature of HCV is that its life cycle depends on lipoprotein metabolism. Viral morphogenesis and secretion follow the very low-density lipoprotein (VLDL) biogenesis pathway and, consequently, infectious HCV in the serum is associated with triglyceride-rich lipoproteins (TRL). Lipoprotein lipase (LPL) hydrolyzes TRL within chylomicrons and VLDL but, independently of its catalytic activity, it has a bridging activity, mediating the hepatic uptake of chylomicrons and VLDL remnants. We previously showed that exogenously added LPL increases HCV binding to hepatoma cells by acting as a bridge between virus-associated lipoproteins and cell surface heparan sulfate, while simultaneously decreasing infection levels. We show here that LPL efficiently inhibits cell infection with two HCV strains produced in hepatoma cells or in primary human hepatocytes transplanted into uPA-SCID mice with fully functional human ApoB-lipoprotein profiles. Viruses produced <em>in vitro</em> or <em>in vivo</em> were separated on iodixanol gradients into low and higher density populations, and the infection of Huh 7.5 cells by both virus populations was inhibited by LPL. The effect of LPL depended on its enzymatic activity. However, the lipase inhibitor tetrahydrolipstatin restored only a minor part of HCV infectivity, suggesting an important role of the LPL bridging function in the inhibition of infection. We followed HCV cell entry by immunoelectron microscopy with anti-envelope and anti-core antibodies. These analyses demonstrated the internalization of virus particles into hepatoma cells and their presence in intracellular vesicles and associated with lipid droplets. In the presence of LPL, HCV was retained at the cell surface. We conclude that LPL efficiently inhibits HCV infection by acting on TRL associated with HCV particles through mechanisms involving its lipolytic function, but mostly its bridging function. These mechanisms lead to immobilization of the virus at the cell surface. HCV-associated lipoproteins may therefore be a promising target for the development of new therapeutic approaches.</p> </div>", "links"=>[], "tags"=>["lipoprotein", "lipase", "inhibits", "hepatitis", "blocking"], "article_id"=>132116, "categories"=>["Cancer", "Biochemistry"], "users"=>["Patrick Maillard", "Marine Walic", "Philip Meuleman", "Farzin Roohvand", "Thierry Huby", "Wilfried Le Goff", "Geert Leroux-Roels", "Eve-Isabelle Pécheur", "Agata Budkowska"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0026637", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Lipoprotein_Lipase_Inhibits_Hepatitis_C_Virus_HCV_Infection_by_Blocking_Virus_Cell_Entry/132116", "title"=>"Lipoprotein Lipase Inhibits Hepatitis C Virus (HCV) Infection by Blocking Virus Cell Entry", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-10-21 00:35:16"}
  • {"files"=>["https://ndownloader.figshare.com/files/721571"], "description"=>"<p>(A) Effect of LPL on virus attachment to Huh7.5 cells. Huh7.5 cells were pre-incubated with various concentrations of LPL (1–9 µg/ml) for 30 min at 4°C. An aliquot of cell culture supernatant containing JFH-1 was incubated with LPL-pretreated Huh7.5 cells for 30 min at 4°C. The cells were washed and the RNA associated with them was extracted. HCV RNA was quantified by RT-qPCR. (B) Effect of LPL on early steps of HCV infection. JFH-1 was first adsorbed onto Huh7.5 cells by incubation for 45 min at 4°C. Cells were washed with cold medium to remove any unbound virus. Complete medium, warmed to 37°C, was then added and incubated with the cells at 37°C. LPL was added to a concentration of 1 µg/ml at various time points (0, 5, 10, 15 or 20 min) after the transfer of cells to 37°C, with or without the addition of 50 µg/ml THL to block its enzymatic activity. Cells were grown for 24 h. RNA was then extracted and HCV RNA was quantified by RT-qPCR. Results are expressed as a percent of RNA as compared with control cells infected in the absence of LPL.</p>", "links"=>[], "tags"=>["affects", "hcv", "attachment", "stages"], "article_id"=>391924, "categories"=>["Virology", "Biochemistry", "Infectious Diseases"], "users"=>["Patrick Maillard", "Marine Walic", "Philip Meuleman", "Farzin Roohvand", "Thierry Huby", "Wilfried Le Goff", "Geert Leroux-Roels", "Eve-Isabelle Pécheur", "Agata Budkowska"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0026637.g006", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_LPL_affects_HCV_attachment_and_early_stages_of_the_virus_cell_cycle_/391924", "title"=>"LPL affects HCV attachment and early stages of the virus cell cycle.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-10-21 00:32:04"}
  • {"files"=>["https://ndownloader.figshare.com/files/721842"], "description"=>"<p>Huh7.5 cells were pre-incubated with 1 µg/ml LPL, as described in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0026637#s2\" target=\"_blank\">Materials and Methods</a>. The viral preparation, concentrated by centrifugation through a sucrose cushion, was incubated with cells at 4°C (T0), then transferred to 37°C and incubated for a further 5 (T5), 10 (T10), 15 (T15) or 20 (T20) min. Cells were washed, fixed and stained with anti-E2 (AP-33) or anti-core (ACAP-27) monoclonal antibodies, followed by secondary, colloidal gold-labeled anti-mouse IgG. LPL 10 min is a representative view of uninfected cells, pretreated with LPL at 4°C and subsequently for 10 min at 37°C, before immunogold labeling with anti-LPL antibodies and processing for TEM. T0, T10 and T20, show immunogold labeling with antibodies directed against HCV E2 (T0) and core protein (T10 and T20). Asterisks denote the presence of one silver-enhanced gold particle. CCP, clathrin-coated pit; CV, clathrin vesicle; M, mitochondrion.</p>", "links"=>[], "tags"=>["microscopy", "cells"], "article_id"=>392194, "categories"=>["Virology", "Biochemistry", "Infectious Diseases"], "users"=>["Patrick Maillard", "Marine Walic", "Philip Meuleman", "Farzin Roohvand", "Thierry Huby", "Wilfried Le Goff", "Geert Leroux-Roels", "Eve-Isabelle Pécheur", "Agata Budkowska"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0026637.g008", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Immunoelectron_microscopy_of_the_infection_of_Huh_7_5_cells_in_the_presence_of_LPL_/392194", "title"=>"Immunoelectron microscopy of the infection of Huh 7.5 cells in the presence of LPL.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-10-21 00:36:34"}
  • {"files"=>["https://ndownloader.figshare.com/files/721977"], "description"=>"<p>Cells were infected and processed as for <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0026637#pone-0026637-g007\" target=\"_blank\">Figures 7</a> and <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0026637#pone-0026637-g008\" target=\"_blank\">8</a>. HCV-bound gold particles after staining with anti-core antibodies were quantified in Huh7.5 cells infected in the absence (panel A) and presence (panel B) of LPL. For each condition and each time point indicated, 30 cells were analyzed, and the number of gold particles present outside (dark gray) and within (light gray) cells is reported. Data are expressed as means±SD.</p>", "links"=>[], "tags"=>["analyses", "immunoelectron"], "article_id"=>392331, "categories"=>["Virology", "Biochemistry", "Infectious Diseases"], "users"=>["Patrick Maillard", "Marine Walic", "Philip Meuleman", "Farzin Roohvand", "Thierry Huby", "Wilfried Le Goff", "Geert Leroux-Roels", "Eve-Isabelle Pécheur", "Agata Budkowska"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0026637.g009", "stats"=>{"downloads"=>1, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Quantitative_analyses_of_immunoelectron_microscopy_/392331", "title"=>"Quantitative analyses of immunoelectron microscopy.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-10-21 00:38:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/721420"], "description"=>"<p>(A) Huh7.5 cells were pre-incubated with 1 µg/ml LPL at 4°C in the presence or absence of 50 µg/ml THL before infection with JFH1. The infected cells were grown for 24 h and HCV RNA was then extracted and quantified by RT-qPCR. (B) THL does not influence HCV replication. Huh7.5 cells were pre-incubated with indicated concentrations of THL before cell infection with JFH-1, as for experiments with LPL. THL was maintained in the medium for 24 h post infection. HCV RNA was then extracted and quantified by RT-qPCR. Results are expressed as a percent of RNA as compared with control cells infected in the absence of LPL and THL.</p>", "links"=>[], "tags"=>["inhibitory", "lpl", "hcvcc", "catalytic"], "article_id"=>391772, "categories"=>["Virology", "Biochemistry", "Infectious Diseases"], "users"=>["Patrick Maillard", "Marine Walic", "Philip Meuleman", "Farzin Roohvand", "Thierry Huby", "Wilfried Le Goff", "Geert Leroux-Roels", "Eve-Isabelle Pécheur", "Agata Budkowska"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0026637.g005", "stats"=>{"downloads"=>3, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_inhibitory_effect_of_LPL_on_HCVcc_infection_is_only_partly_related_to_its_catalytic_activity_/391772", "title"=>"The inhibitory effect of LPL on HCVcc infection is only partly related to its catalytic activity.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-10-21 00:29:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/721193"], "description"=>"<p>The pooled peak fractions of the low- and high-density virus populations obtained after centrifugation through iodixanol gradients of JFH1 grown in cell culture (A) and serum samples from the m-JFH1 chimeric mouse model (B) (both gradients are shown in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0026637#pone-0026637-g002\" target=\"_blank\">Figure 2</a>) were used to infect cells in the presence or absence of 1 µg/ml LPL, as described in the <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0026637#s2\" target=\"_blank\">Materials and Methods</a> section. Cells were grown for 48 h at 37°C and HCV RNA was extracted and quantified by RT-qPCR. The results were normalized with respect to the cellular gene GAPDH, with the GAPDH Control Kit. The data are expressed as the amount of HCV RNA detected in cells infected with the pooled fractions from the two major virus populations in the presence of LPL as compared with the amount of HCV RNA in cells infected with the same fractions in the absence of LPL, expressed as a percentage.</p>", "links"=>[], "tags"=>["low-", "high-density", "populations", "iodixanol", "gradients"], "article_id"=>391541, "categories"=>["Virology", "Biochemistry", "Infectious Diseases"], "users"=>["Patrick Maillard", "Marine Walic", "Philip Meuleman", "Farzin Roohvand", "Thierry Huby", "Wilfried Le Goff", "Geert Leroux-Roels", "Eve-Isabelle Pécheur", "Agata Budkowska"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0026637.g003", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cell_infection_with_low_and_high_density_virus_populations_from_iodixanol_gradients_in_the_presence_or_absence_of_LPL_/391541", "title"=>"Cell infection with low- and high-density virus populations from iodixanol gradients in the presence or absence of LPL.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-10-21 00:25:41"}
  • {"files"=>["https://ndownloader.figshare.com/files/721030"], "description"=>"<p>The supernatants from infected Huh7.5 cells producing JFH-1 (JFH-1, shown in A and B) and J6/JFH-1 (shown in E) were subjected to isopycnic centrifugation through iodixanol gradients, as described in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0026637#s2\" target=\"_blank\">Materials and Methods</a>. Pooled serum samples from the chimeric uPA-SCID mice were also subjected to centrifugation on the same type of gradient. Representative profiles are shown in C and D for mice inoculated with JFH-1 (mJFH-1) and in F for mice inoculated with J6/JFH-1 (mJ6/JFH-1). HCV core antigen in gradient fractions was quantified by ELISA, HCV RNA was quantified by RT-qPCR, and ApoB and cholesterol were determined by ELISA. Infectivity for fractionated J6/JFH-1 (representative for both strains) grown in Huh7.5 cells is shown in E and that for the corresponding mouse serum (mJ6/JFH-1) is shown in F. The fractions (25 µl) were used to infect Huh7.5 cells. Cells were incubated for 48 h at 37°C; total RNA was then extracted and HCV-RNA levels were quantified by RT-qPCR. The results were normalized, taking into account the initial HCV-RNA content in each sample analyzed, as determined by RT-qPCR, and are expressed as a ratio of these two values.</p>", "links"=>[], "tags"=>["gradient", "jfh-1", "strains", "produced"], "article_id"=>391379, "categories"=>["Virology", "Biochemistry", "Infectious Diseases"], "users"=>["Patrick Maillard", "Marine Walic", "Philip Meuleman", "Farzin Roohvand", "Thierry Huby", "Wilfried Le Goff", "Geert Leroux-Roels", "Eve-Isabelle Pécheur", "Agata Budkowska"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0026637.g002", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Iodixanol_gradient_analysis_of_the_JFH_1_and_J6_JFH_1_strains_produced_in_vitro_and_in_vivo_/391379", "title"=>"Iodixanol gradient analysis of the JFH-1 and J6/JFH-1 strains produced <i>in vitro</i> and <i>in vivo</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-10-21 00:22:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/721313"], "description"=>"<p>Huh 7.5 cells were washed with medium without FCS and pre-incubated with LPL on ice. Purified VLDL were then added and, after 30 min, cells were transferred to 37°C and incubated for a further 2 h. The effect of LPL on VLDL uptake was shown by the increase in the amounts of both total triglycerides (TG) associated with cells in the presence of LPL. Cellular levels of TC and TG were also assessed in the presence of LPL and THL or heparin. (A) Hydrolysis of VLDL by LPL increased cellular TG levels due to the intracellular accumulation of fatty acids. This process was inhibited by THL, but was insensitive to the action of heparin, as it did not involve “bridging” mechanisms. (B) LPL increased the levels of TC in the cells in the presence VLDL. The effect of LPL was abolished by adding either THL, an inhibitor of LPL enzyme activity, or heparin, which prevents LPL from associating with proteoglycans. Thus, both catalytic and bridging activities were involved.</p>", "links"=>[], "tags"=>["lpl", "vldl", "hydrolysis", "uptake"], "article_id"=>391666, "categories"=>["Virology", "Biochemistry", "Infectious Diseases"], "users"=>["Patrick Maillard", "Marine Walic", "Philip Meuleman", "Farzin Roohvand", "Thierry Huby", "Wilfried Le Goff", "Geert Leroux-Roels", "Eve-Isabelle Pécheur", "Agata Budkowska"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0026637.g004", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Analysis_of_the_influence_of_LPL_on_VLDL_hydrolysis_and_uptake_by_Huh_7_5_cells_/391666", "title"=>"Analysis of the influence of LPL on VLDL hydrolysis and uptake by Huh 7.5 cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-10-21 00:27:46"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"5", "full-text"=>"6", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"9"}
  • {"unique-ip"=>"9", "full-text"=>"12", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"10"}
  • {"unique-ip"=>"3", "full-text"=>"2", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"11"}
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  • {"unique-ip"=>"2", "full-text"=>"2", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"4"}
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  • {"unique-ip"=>"9", "full-text"=>"8", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"8"}
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  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
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  • {"unique-ip"=>"10", "full-text"=>"10", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
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  • {"unique-ip"=>"11", "full-text"=>"8", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"9"}
  • {"unique-ip"=>"8", "full-text"=>"8", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"10"}
  • {"unique-ip"=>"5", "full-text"=>"4", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2019", "month"=>"12"}
  • {"unique-ip"=>"9", "full-text"=>"8", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2020", "month"=>"2"}
  • {"unique-ip"=>"13", "full-text"=>"12", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2020", "month"=>"3"}
  • {"unique-ip"=>"8", "full-text"=>"7", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"4"}
  • {"unique-ip"=>"13", "full-text"=>"13", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"5"}
  • {"unique-ip"=>"8", "full-text"=>"7", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"6"}
  • {"unique-ip"=>"4", "full-text"=>"5", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"7"}
  • {"unique-ip"=>"12", "full-text"=>"10", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"10", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"8"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"11", "supp-data"=>"1", "cited-by"=>"1", "year"=>"2020", "month"=>"9"}

Relative Metric

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