Aqueous Extracts of the Marine Brown Alga Lobophora variegata Inhibit HIV-1 Infection at the Level of Virus Entry into Cells
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{"title"=>"Aqueous extracts of the marine brown alga Lobophora variegata inhibit HIV-1 infection at the level of virus entry into cells", "type"=>"journal", "authors"=>[{"first_name"=>"Stephan", "last_name"=>"Kremb", "scopus_author_id"=>"37052515200"}, {"first_name"=>"Markus", "last_name"=>"Helfer", "scopus_author_id"=>"25960064000"}, {"first_name"=>"Birgit", "last_name"=>"Kraus", "scopus_author_id"=>"8443108300"}, {"first_name"=>"Horst", "last_name"=>"Wolff", "scopus_author_id"=>"10045146300"}, {"first_name"=>"Christian", "last_name"=>"Wild", "scopus_author_id"=>"35320721300"}, {"first_name"=>"Martha", "last_name"=>"Schneider", "scopus_author_id"=>"34977392800"}, {"first_name"=>"Christian R.", "last_name"=>"Voolstra", "scopus_author_id"=>"25224158700"}, {"first_name"=>"Ruth", "last_name"=>"Brack-Werner", "scopus_author_id"=>"7004196231"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-84929050861", "pui"=>"373801958", "doi"=>"10.1371/journal.pone.0103895", "isbn"=>"1932-6203", "sgr"=>"84929050861", "pmid"=>"25144758"}, "id"=>"8a6e0760-42af-316d-b8a9-f3479c4054cb", "abstract"=>"In recent years, marine algae have emerged as a rich and promising source of molecules with potent activities against various human pathogens. The widely distributed brown alga Lobophora variegata that is often associated with tropical coral reefs exerts strong antibacterial and antiprotozoal effects, but so far has not been associated with specific anti-viral activities. This study investigated potential HIV-1 inhibitory activity of L. variegata collected from different geographical regions, using a cell-based full replication HIV-1 reporter assay. Aqueous L. variegata extracts showed strong inhibitory effects on several HIV-1 strains, including drug-resistant and primary HIV-1 isolates, and protected even primary cells (PBMC) from HIV-1-infection. Anti-viral potency was related to ecological factors and showed clear differences depending on light exposition or epiphyte growth. Assays addressing early events of the HIV-1 replication cycle indicated that L. variegata extracts inhibited entry of HIV-1 into cells at a pre-fusion step possibly by impeding mobility of virus particles. Further characterization of the aqueous extract demonstrated that even high doses had only moderate effects on viability of cultured and primary cells (PBMCs). Imaging-based techniques revealed extract effects on the plasma membrane and actin filaments as well as induction of apoptosis at concentrations exceeding EC50 of anti-HIV-1 activity by more than 400 fold. In summary, we show for the first time that L. variegata extracts inhibit HIV-1 entry, thereby suggesting this alga as promising source for the development of novel HIV-1 inhibitors.", "link"=>"http://www.mendeley.com/research/aqueous-extracts-marine-brown-alga-lobophora-variegata-inhibit-hiv1-infection-level-virus-entry-cell", "reader_count"=>26, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Researcher"=>5, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>2, "Student > Master"=>6, "Other"=>1, "Student > Bachelor"=>3, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Researcher"=>5, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>2, "Student > Master"=>6, "Other"=>1, "Student > Bachelor"=>3, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Environmental Science"=>4, "Medicine and Dentistry"=>2, "Agricultural and Biological Sciences"=>14, "Pharmacology, Toxicology and Pharmaceutical Science"=>3, "Chemistry"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Chemistry"=>{"Chemistry"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>14}, "Unspecified"=>{"Unspecified"=>1}, "Environmental Science"=>{"Environmental Science"=>4}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>3}}, "reader_count_by_country"=>{"Saudi Arabia"=>1, "Brazil"=>1}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1646706"], "description"=>"<p><b>A</b>: Time-of-compound addition dependent inhibition of HIV-1 replication. HIV-1 indicator cells were treated with various reference compounds targeting approved steps of HIV-1 replication (GRFT: virus attachment; T-20: virus/cell fusion; AZT: reverse transcription, competitive; EFV: reverse transcription, non-competitive) and the <i>L. variegata</i> aqueous extract at concentrations of 2× EC50. All LC5-RIC indicator cell cultures were exposed to HIV-1 LAI. at time point 0 with test and reference compounds were added to the cells at different time points. At least 10 different time points in triplicates were measured for each compound. <b>B</b>: Analysis of HIV-1 attachment using GFP-labeled HIV-1 particles. HIV-1 indicator cells were exposed to the HIV-1 NL4-3 Gag-iGFP reporter virus for 4 hours in the presence of the fusion inhibitor T20 and test compounds (250 µg/ml aqueous <i>L. variegata</i> extract or 50 nM Griffithsin). Nuclei were stained with DAPI.</p>", "links"=>[], "tags"=>["variegata extracts", "ec", "pbmc", "Marine Brown Alga Lobophora variegata Inhibit HIV", "alga Lobophora variegata"], "article_id"=>1148699, "categories"=>["Biological Sciences"], "users"=>["Stephan Kremb", "Markus Helfer", "Birgit Kraus", "Horst Wolff", "Christian Wild", "Martha Schneider", "Christian R. Voolstra", "Ruth Brack-Werner"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0103895.g004", "stats"=>{"downloads"=>2, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Analysis_of_the_mechanism_of_action_of_the_L_variegata_extract_/1148699", "title"=>"Analysis of the mechanism-of-action of the <i>L. variegata</i> extract.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-08-21 04:33:16"}
  • {"files"=>["https://ndownloader.figshare.com/files/1646714"], "description"=>"<div><p>In recent years, marine algae have emerged as a rich and promising source of molecules with potent activities against various human pathogens. The widely distributed brown alga <i>Lobophora variegata</i> that is often associated with tropical coral reefs exerts strong antibacterial and antiprotozoal effects, but so far has not been associated with specific anti-viral activities. This study investigated potential HIV-1 inhibitory activity of <i>L. variegata</i> collected from different geographical regions, using a cell-based full replication HIV-1 reporter assay. Aqueous <i>L. variegata</i> extracts showed strong inhibitory effects on several HIV-1 strains, including drug-resistant and primary HIV-1 isolates, and protected even primary cells (PBMC) from HIV-1-infection. Anti-viral potency was related to ecological factors and showed clear differences depending on light exposition or epiphyte growth. Assays addressing early events of the HIV-1 replication cycle indicated that <i>L. variegata</i> extracts inhibited entry of HIV-1 into cells at a pre-fusion step possibly by impeding mobility of virus particles. Further characterization of the aqueous extract demonstrated that even high doses had only moderate effects on viability of cultured and primary cells (PBMCs). Imaging-based techniques revealed extract effects on the plasma membrane and actin filaments as well as induction of apoptosis at concentrations exceeding EC<sub>50</sub> of anti-HIV-1 activity by more than 400 fold. In summary, we show for the first time that <i>L. variegata</i> extracts inhibit HIV-1 entry, thereby suggesting this alga as promising source for the development of novel HIV-1 inhibitors.</p></div>", "links"=>[], "tags"=>["variegata extracts", "ec", "pbmc", "Marine Brown Alga Lobophora variegata Inhibit HIV", "alga Lobophora variegata"], "article_id"=>1148707, "categories"=>["Biological Sciences"], "users"=>["Stephan Kremb", "Markus Helfer", "Birgit Kraus", "Horst Wolff", "Christian Wild", "Martha Schneider", "Christian R. Voolstra", "Ruth Brack-Werner"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0103895", "stats"=>{"downloads"=>0, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Aqueous_Extracts_of_the_Marine_Brown_Alga_Lobophora_variegata_Inhibit_HIV_1_Infection_at_the_Level_of_Virus_Entry_into_Cells/1148707", "title"=>"Aqueous Extracts of the Marine Brown Alga <i>Lobophora variegata</i> Inhibit HIV-1 Infection at the Level of Virus Entry into Cells", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-08-21 04:33:16"}
  • {"files"=>["https://ndownloader.figshare.com/files/1646699"], "description"=>"<p><b>A</b>: Dose-dependent inhibition of HIV-1 (strain HIV-LAI) replication in LC5-RIC reporter cells by aqueous extracts from specimens collected at various geographical locations including the Caribbean (Turneffe Reef, Belize), northern Red Sea (Sinai, Egypt, Canyon Reef) and the central Red Sea (Rose Reef, Kingdom of Saudi Arabia). Cells were treated with serial dilutions of the aqueous <i>L. variegata</i> extract (ranging from 3.2 up to 100 µg/ml) in triplicates and exposed to the HIV-1 LAI strain. <b>B</b>: Effects of different concentrations of <i>L. variegata</i> extract (collected from Turneffe Reef, Belize) on viability of indicator cells were measured by the colorimetric MTT assay. LC5-RIC reporter cells were treated with serial dilutions (ranging from 3.1 up to 400 µg/ml) of the aqueous <i>L. variegata</i> extract for 48 hours. Data are given relative to untreated cells (100%).</p>", "links"=>[], "tags"=>["variegata extracts", "ec", "pbmc", "Marine Brown Alga Lobophora variegata Inhibit HIV", "alga Lobophora variegata"], "article_id"=>1148692, "categories"=>["Biological Sciences"], "users"=>["Stephan Kremb", "Markus Helfer", "Birgit Kraus", "Horst Wolff", "Christian Wild", "Martha Schneider", "Christian R. Voolstra", "Ruth Brack-Werner"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0103895.g001", "stats"=>{"downloads"=>0, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Dose_dependent_inhibition_of_HIV_1_replication_and_vitality_of_reporter_cells_/1148692", "title"=>"Dose-dependent inhibition of HIV-1 replication and vitality of reporter cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-08-21 04:33:16"}
  • {"files"=>["https://ndownloader.figshare.com/files/1646713"], "description"=>"<p>The panel includes viruses using the chemokine co-receptor CXCR4 (X4 tropic) or CCR5 (R5 tropic), a multi-drug-resistant HIV-1 variant with patient-derived <i>reverse transcriptase</i> mutations, a primary HIV-1 isolate isolated from cerebrospinal fluid, as well as HV-1 virus particles bearing the G-protein of the vesicular stomatitis virus in the envelope. EC<sub>50</sub> values (µg aqueous extract per ml cell culture medium) were calculated by SigmaPlot and R-squared parameters are given.</p>", "links"=>[], "tags"=>["variegata extracts", "ec", "pbmc", "Marine Brown Alga Lobophora variegata Inhibit HIV", "alga Lobophora variegata"], "article_id"=>1148706, "categories"=>["Biological Sciences"], "users"=>["Stephan Kremb", "Markus Helfer", "Birgit Kraus", "Horst Wolff", "Christian Wild", "Martha Schneider", "Christian R. Voolstra", "Ruth Brack-Werner"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0103895.t001", "stats"=>{"downloads"=>1, "page_views"=>18, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Evaluation_of_anti_HIV_1_activity_of_aqueous_L_variegata_extract_activity_with_a_panel_of_HIV_1_strains_and_LC5_RIC_indicator_cells_/1148706", "title"=>"Evaluation of anti-HIV-1 activity of aqueous <i>L. variegata</i> extract activity with a panel of HIV-1 strains and LC5-RIC indicator cells.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-08-21 04:33:16"}
  • {"files"=>["https://ndownloader.figshare.com/files/1646708"], "description"=>"<p><b>A.</b> Reduction of input HIV-1 viral RNA levels by treatment with <i>L. variegata</i> aqueous extract. LC5-CD4 cells were infected with HIV-1 in the absence or presence <i>of L. variegata</i> aqueous extract. 4 hours p.i. cells were washed extensively to remove inoculum and subsequently total RNA was isolated. After reverse transcription, qPCR was performed to quantify viral RNA levels. HIV-1 transcript levels were normalized to RPII levels. Means and standard deviations are shown in relation to untreated/uninfected cells in percent. <b>B.</b> Reduction of HIV-1 DNA loads by treatment with <i>L. variegata</i> aqueous extract. LC5-CD4 cells were infected with HIV-1 in the absence or presence of <i>L. variegata</i> aqueous extract. 24 hours later, cells were washed extensively to remove inoculum RNA isolated and cDNA produced from RNA. To quantify viral DNA loads, absolute qPCR was performed. Means and standard deviations are shown in relation to untreated/uninfected samples in percent.</p>", "links"=>[], "tags"=>["variegata extracts", "ec", "pbmc", "Marine Brown Alga Lobophora variegata Inhibit HIV", "alga Lobophora variegata"], "article_id"=>1148701, "categories"=>["Biological Sciences"], "users"=>["Stephan Kremb", "Markus Helfer", "Birgit Kraus", "Horst Wolff", "Christian Wild", "Martha Schneider", "Christian R. Voolstra", "Ruth Brack-Werner"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0103895.g005", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_L_variegata_aqueous_extract_inhibits_HIV_entry_/1148701", "title"=>"<i>L. variegata</i> aqueous extract inhibits HIV entry.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-08-21 04:33:16"}
  • {"files"=>["https://ndownloader.figshare.com/files/1646702"], "description"=>"<p><b>A</b>: Effects of high extract concentrations on cell loss (left) and nuclear shape of HeLa cells as an indicator of either apoptosis or necrosis (right). <b>B</b>: CYTOO chip single cell assay for morphometry: microscopic images of HeLa cells spotted on fibronectin Y-patterns either control- (top row) or extract- (bottom row) treated (50 mg ml<sup>−1</sup>, nuclei in blue, actin in green, membrane in orange/red). <b>C</b>: Results of automatic feature extraction by High Content Analysis done with approx. 150 cells per experiment and treatment. Asterisks indicate statistical significance (***p<0,001).</p>", "links"=>[], "tags"=>["variegata extracts", "ec", "pbmc", "Marine Brown Alga Lobophora variegata Inhibit HIV", "alga Lobophora variegata"], "article_id"=>1148695, "categories"=>["Biological Sciences"], "users"=>["Stephan Kremb", "Markus Helfer", "Birgit Kraus", "Horst Wolff", "Christian Wild", "Martha Schneider", "Christian R. Voolstra", "Ruth Brack-Werner"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0103895.g002", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_treatment_with_different_concentrations_of_L_variegata_extracts_on_multiple_cellular_parameters_/1148695", "title"=>"Effects of treatment with different concentrations of <i>L. variegata</i> extracts on multiple cellular parameters.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-08-21 04:33:16"}
  • {"files"=>["https://ndownloader.figshare.com/files/1646703"], "description"=>"<p><b>A</b>: Dose-dependent inhibition of HIV-1 replication in primary cells treated with <i>L. variegata</i> aqueous extract. Peripheral blood mononuclear cells (PBMC) were isolated from whole blood and exposed to the lymphotropic variant HIV1-LAI. Pooled PBMCs were stimulated by treatment with IL-2 for 72 hours, followed by the addition of virus inoculum (HIV-1 LAI) and diluted extracts and continued incubation for 4 days under standard cell culture conditions. The production of infectious HIV-1 progeny was titrated on LC5-RIC indicator cells. <b>B</b>: Vitality of HIV-1-infected PBMC at corresponding extract concentrations.</p>", "links"=>[], "tags"=>["variegata extracts", "ec", "pbmc", "Marine Brown Alga Lobophora variegata Inhibit HIV", "alga Lobophora variegata"], "article_id"=>1148696, "categories"=>["Biological Sciences"], "users"=>["Stephan Kremb", "Markus Helfer", "Birgit Kraus", "Horst Wolff", "Christian Wild", "Martha Schneider", "Christian R. Voolstra", "Ruth Brack-Werner"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0103895.g003", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_the_L_variegata_extract_on_HIV_1_infection_of_primary_cells_/1148696", "title"=>"Effects of the <i>L. variegata</i> extract on HIV-1 infection of primary cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-08-21 04:33:16"}
  • {"files"=>["https://ndownloader.figshare.com/files/1646711"], "description"=>"<p><b>A</b>: Comparison of extract activities of specimens from the Northern Red Sea, collected from sunny or shady locations. <b>B</b>: Comparison of extract activities of specimens from the Caribbean with or without overgrowth by epiphytes. Epiphytes were removed before extraction of <i>L. variegata</i>. All extracts were tested on LC5-RIC reporter cells using the HIV-1 strain HIV-LAI.</p>", "links"=>[], "tags"=>["variegata extracts", "ec", "pbmc", "Marine Brown Alga Lobophora variegata Inhibit HIV", "alga Lobophora variegata"], "article_id"=>1148705, "categories"=>["Biological Sciences"], "users"=>["Stephan Kremb", "Markus Helfer", "Birgit Kraus", "Horst Wolff", "Christian Wild", "Martha Schneider", "Christian R. Voolstra", "Ruth Brack-Werner"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0103895.g006", "stats"=>{"downloads"=>0, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_different_growth_conditions_of_L_variegata_on_the_HIV_1_inhibitory_potential_/1148705", "title"=>"Effects of different growth conditions of <i>L. variegata</i> on the HIV-1 inhibitory potential.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-08-21 04:33:16"}

PMC Usage Stats | Further Information

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Relative Metric

{"start_date"=>"2014-01-01T00:00:00Z", "end_date"=>"2014-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences/Organisms", "average_usage"=>[310]}, {"subject_area"=>"/Earth sciences/Marine and aquatic sciences", "average_usage"=>[343]}, {"subject_area"=>"/Medicine and health sciences", "average_usage"=>[285]}, {"subject_area"=>"/Medicine and health sciences/Pathology and laboratory medicine", "average_usage"=>[287]}]}
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