Toll-Like Receptor 3 (TLR3) Plays a Major Role in the Formation of Rabies Virus Negri Bodies
Publication Date
February 27, 2009
Journal
PLOS Pathogens
Authors
Pauline Ménager, Pascal Roux, Françoise Mégret, Jean Pierre Bourgeois, et al
Volume
5
Issue
2
Pages
e1000315
DOI
https://dx.plos.org/10.1371/journal.ppat.1000315
Publisher URL
http://journals.plos.org/plospathogens/article?id=10.1371%2Fjournal.ppat.1000315
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/19247444
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2642728
Europe PMC
http://europepmc.org/abstract/MED/19247444
Web of Science
000263928000006
Scopus
61449235415
Mendeley
http://www.mendeley.com/research/tolllike-receptor-3-tlr3-plays-major-role-formation-rabies-virus-negri-bodies
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Mendeley | Further Information

{"title"=>"Toll-Like Receptor 3 (TLR3) Plays a Major Role in the Formation of Rabies Virus Negri Bodies", "type"=>"journal", "authors"=>[{"first_name"=>"Pauline", "last_name"=>"Ménager"}, {"first_name"=>"Pascal", "last_name"=>"Roux"}, {"first_name"=>"Françoise", "last_name"=>"Mégret"}, {"first_name"=>"Jean-Pierre", "last_name"=>"Bourgeois"}, {"first_name"=>"Anne-Marie", "last_name"=>"Le Sourd"}, {"first_name"=>"Anne", "last_name"=>"Danckaert"}, {"first_name"=>"Mireille", "last_name"=>"Lafage"}, {"first_name"=>"Christophe", "last_name"=>"Préhaud"}, {"first_name"=>"Monique", "last_name"=>"Lafon"}], "year"=>2009, "source"=>"PLoS Pathogens", "identifiers"=>{"doi"=>"10.1371/journal.ppat.1000315", "pmid"=>"19247444", "issn"=>"1553-7374", "isbn"=>"1553-7374 (Electronic)\\r1553-7366 (Linking)"}, "id"=>"e4300c17-2515-3f25-8fb1-1404e44aeca2", "abstract"=>"Human neurons express the innate immune response receptor, Toll-like receptor 3 (TLR3). TLR3 levels are increased in pathological conditions such as brain virus infection. Here, we further investigated the production, cellular localisation, and function of neuronal TLR3 during neuronotropic rabies virus (RABV) infection in human neuronal cells. Following RABV infection, TLR3 is not only present in endosomes, as observed in the absence of infection, but also in detergent-resistant perinuclear inclusion bodies. As well as TLR3, these inclusion bodies contain the viral genome and viral proteins (N and P, but not G). The size and composition of inclusion bodies and the absence of a surrounding membrane, as shown by electron microscopy, suggest they correspond to the previously described Negri Bodies (NBs). NBs are not formed in the absence of TLR3, and TLR3(-/-) mice -- in which brain tissue was less severely infected -- had a better survival rate than WT mice. These observations demonstrate that TLR3 is a major molecule involved in the spatial arrangement of RABV-induced NBs and viral replication. This study shows how viruses can exploit cellular proteins and compartmentalisation for their own benefit.", "link"=>"http://www.mendeley.com/research/tolllike-receptor-3-tlr3-plays-major-role-formation-rabies-virus-negri-bodies", "reader_count"=>55, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>4, "Researcher"=>11, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>17, "Student > Postgraduate"=>2, "Student > Master"=>3, "Other"=>3, "Student > Bachelor"=>8, "Professor"=>3}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>4, "Researcher"=>11, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>17, "Student > Postgraduate"=>2, "Student > Master"=>3, "Other"=>3, "Student > Bachelor"=>8, "Professor"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Biochemistry, Genetics and Molecular Biology"=>4, "Agricultural and Biological Sciences"=>28, "Medicine and Dentistry"=>7, "Neuroscience"=>1, "Veterinary Science and Veterinary Medicine"=>5, "Social Sciences"=>1, "Immunology and Microbiology"=>6}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>7}, "Neuroscience"=>{"Neuroscience"=>1}, "Social Sciences"=>{"Social Sciences"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>6}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>28}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>4}, "Unspecified"=>{"Unspecified"=>3}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>5}}, "reader_count_by_country"=>{"Colombia"=>1, "United States"=>2, "Japan"=>1, "Portugal"=>1}, "group_count"=>0}

CrossRef

Scopus | Further Information

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  • {"files"=>["https://ndownloader.figshare.com/files/907987"], "description"=>"<p>Comparison of RABV infection in TLR3<sup>−/−</sup> and C57Bl6 (WT) mice. (A) Kaplan-Meier survival curves for TLR3<sup>−/−</sup> (gray curve and circles) and WT (black curve and triangles) mice after injection of RABV (n = 8 WT and n = 9 KO mice). Chi-square = 2.24 (<3,6) with a degree of freedom of 1 and a significance of P (0.134). The hazard ratio was 0.2882. (B) Cumulative clinical scores are significantly different at P value<0.05. (C) Viral load (RABV genome) was measured by relative Q-PCR at day 11 pi in the brain of TLR3<sup>−/−</sup> and WT mice (three mice each). Histogram represents means with SD. P value = 0.002. Two separate experiments were performed.</p>", "links"=>[], "tags"=>["mice", "neuroinvasiveness"], "article_id"=>578435, "categories"=>["Immunology", "Medicine", "Infectious Diseases"], "users"=>["Pauline Ménager", "Pascal Roux", "Françoise Mégret", "Jean-Pierre Bourgeois", "Anne-Marie Le Sourd", "Anne Danckaert", "Mireille Lafage", "Christophe Préhaud", "Monique Lafon"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1000315.g009", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Rabies_is_less_severe_in_TLR3_8722_8722_mice_and_neuroinvasiveness_is_reduced_/578435", "title"=>"Rabies is less severe in TLR3<sup>−/−</sup> mice and neuroinvasiveness is reduced.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-02-27 02:20:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/907768"], "description"=>"<p>To analyze the role of microtubules in the NBs outcome, 24 h RABV–infected SK-N-SH cells were either treated with colcemid (a drug which disrupts microtubule network), with PBS (vehicle), or in the absence of drug for 24 h. (A) Efficiency of colcemid on microtubules stability was assayed by staining 24 h PBS–treated (upper panels), and colcemid treated cells (lower panels) with an Ab directed against tubulin (red). Nuclei are stained with DAPI (blue). Bar = 10 µm. (B and C) Effect of colcemid on size and number of NBs per cell in 48 h RABV–infected cells. After fixation, cells were stained with viral NC Ab. Size (units = pixels) and number of viral inclusions were determined and analysed using Acapella software. Infection levels were similar in presence or in absence of colcemid. (B) Colcemid treatment modifies the size of NBs in the culture by increasing the number of NBs of intermediary range size (200–350 pixels). (C) Colcemid treatment interrupts the increase of NBs per cell (>8 NBs/cell) seen 48 h after infection. In absence of treatment 75% of 48 h RABV infected cells contains >8 NBs per cell. This percentage is reduced by one half (35–40%) after a 24 h colcemid treatment. Graphs represent means and SD (standard deviation).</p>", "links"=>[], "tags"=>["microtubule", "nbs"], "article_id"=>578220, "categories"=>["Immunology", "Medicine", "Infectious Diseases"], "users"=>["Pauline Ménager", "Pascal Roux", "Françoise Mégret", "Jean-Pierre Bourgeois", "Anne-Marie Le Sourd", "Anne Danckaert", "Mireille Lafage", "Christophe Préhaud", "Monique Lafon"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1000315.g007", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Involvement_of_the_microtubule_network_in_NBs_dynamics_/578220", "title"=>"Involvement of the microtubule network in NBs dynamics.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-02-27 02:17:00"}
  • {"files"=>["https://ndownloader.figshare.com/files/907271"], "description"=>"<p>(A) RABV-infected Ntera-2clD/1 cells were co-stained with Ab directed against the viral nucleocapsid (NC green), TLR3 (Ab Sc-C20, red), and Hoechst (nuclei, blue). In all infected cells TLR3–positive aggregates colocalize with viral NC forming perinuclear structures (Merge, lower panel). Bar = 10 µm. (B) RABV-infected Ntera-2clD/1 cells were co-stained with Ab directed against the viral nucleocapsid (NC green), TLR3 (Ab Sc-C20, red), and Hoechst (nuclei in blue). T is the transmission picture. The merged picture shows that NC accumulates with some perinuclear TLR3–positive aggregates (arrow). These perinuclear aggregates are visible in the transmission image. M is the 3D rendering (Imaris, Bitplane AG) after deconvolution (Huygens, Scientific Volume, Imaging). TLR3 constitutes the core of the structure (red internal core), surrounded by a coating of viral NC (green halo). Nuclear material was not present in these structures. Bar = 5 µm. (C) Enlargement of a 3D rendering of a TLR3–containing aggregate, showing the typical organisation of RABV–induced inclusions bodies composed of an inner core (TLR3 in red) surrounded by a viral NC protein cage (green halo). Diameter of the aggregate is 2.7 µm.</p>", "links"=>[], "tags"=>["viral", "nc", "proteins", "assembled", "spherical", "perinuclear"], "article_id"=>577717, "categories"=>["Immunology", "Medicine", "Infectious Diseases"], "users"=>["Pauline Ménager", "Pascal Roux", "Françoise Mégret", "Jean-Pierre Bourgeois", "Anne-Marie Le Sourd", "Anne Danckaert", "Mireille Lafage", "Christophe Préhaud", "Monique Lafon"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1000315.g003", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_TLR3_and_viral_NC_proteins_are_assembled_in_spherical_perinuclear_structures_/577717", "title"=>"TLR3 and viral NC proteins are assembled in spherical perinuclear structures.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-02-27 02:08:37"}
  • {"files"=>["https://ndownloader.figshare.com/files/907028"], "description"=>"<p>(A) Neuronal precursors (Ntera-2clD/1), human post-mitotic neurons (NT2-N), and neuroblastoma cells (SK-N-SH) express <i>TLR3</i> transcripts (size 527 bp), as shown by RT–PCR. 18S was used as a reporter gene. (B) RT–PCR was performed with a pair of primers corresponding to exon 4 of <i>TLR3</i>. The amplified fragments from Ntera-2clD/1, astrocytes (U373 MG), microglia (CHME) (upper panel), or SK-N-SH (lower panel) were a similar size (345 bp), suggesting that <i>TLR3</i> does not undergo alternative splicing in these neural cell types. Alternative splicing was not observed during infection, monitored by viral <i>N protein</i> (N) transcription (lower panel). M denotes molecular weight. (C) TLR3 protein was detected in RIPA lysates of non-infected (NI) and RABV–infected Ntera-2clD/1 cells using a mAb (cloneIMG315-A) directed to the NH2 terminal of TLR3. Infection was monitored by detection of the viral N (N) and P (P) proteins. TLR3 protein (102 kD) was not upregulated by infection, as shown by quantification of TLR3 (histogram) using calnexin (Cx) as a standard (GeneTools, Syngene). The same results were obtained for proteins extracted using Phosphosafe extraction buffer. Graph was generated using GraphPad Prism. (D) Cytofluorimetry analysis showed that TLR3 has an intracellular location and cannot be detected at the surface of SK-N-SH cells. This distribution pattern was not modified by infection. The viral nucleocapsid (NC)—left panels—is strictly intracellular, and its detection was thus used as a control for membrane impermeability. The solid line corresponds to RABV–infected cells and the histogram to NI cells. TLR3 protein (right panels) was analysed by flow cytometry using a polyclonal antibody directed to the NH2 terminal of TLR3 (Sc-Q18) in NI and RABV–infected cells. Histograms correspond to secondary Ab and solid lines to TLR3 staining. Numbers represent the percentages of cells positive for TLR3 or NC proteins. These results are representative of at least 5 separate experiments.</p>", "links"=>[], "tags"=>["tlr3", "non-infected", "neuronal"], "article_id"=>577478, "categories"=>["Immunology", "Medicine", "Infectious Diseases"], "users"=>["Pauline Ménager", "Pascal Roux", "Françoise Mégret", "Jean-Pierre Bourgeois", "Anne-Marie Le Sourd", "Anne Danckaert", "Mireille Lafage", "Christophe Préhaud", "Monique Lafon"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1000315.g001", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expression_of_TLR3_in_non_infected_and_RABV_8211_infected_neuronal_cells_/577478", "title"=>"Expression of TLR3 in non-infected and RABV–infected neuronal cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-02-27 02:04:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/907665"], "description"=>"<p>(A) RABV–infected cells were immunostained with Ab against viral NC (1 and 4) and co-stained with either anti-pan-tubulin (2 and 3) or anti-vimentin Ab (5 and 6). Merged images are shown in 3 and 6. NBs (arrows) are associated with tubulin fibres (3); however, in contrast to canonical aggresomes, NBs are not surrounded by a ‘cage’ of the intermediate filament protein vimentin (6). N = nucleus. Bars = 10 µm. (B) RABV–infected cells were co-stained with Abs directed against viral NC (1) and anti Hsp70 (2). NBs are associated with the chaperone Hsp70, as shown by confocal analysis and 3D modelling [3 is the merged image; 4 is a 3D rendering (Imaris®, Bitplane AG) after deconvolution (Huygens, Scientific Volume, Imaging) of the perinuclear area (white square) from 3]. Bar = 5 µm. (C) NBs (green) are not formed at the MTOC/centrosome, detected using an antibody directed against γ-tubulin (arrows). N = nucleus. Bar = 10 µm. (D) RABV–infected cell lysates were separated after detergent treatment, into soluble (S) and insoluble (IS) fractions. The IS fraction contained the insoluble cytoskeletal protein vimentin but not tubulin or calnexin (Western Blot, upper panel). The IS fraction also contained NBs, which showed positively with anti-NC (green) and anti-TLR3 Ab (red). Bars = 2 µm.</p>", "links"=>[], "tags"=>["nbs", "characteristics"], "article_id"=>578115, "categories"=>["Immunology", "Medicine", "Infectious Diseases"], "users"=>["Pauline Ménager", "Pascal Roux", "Françoise Mégret", "Jean-Pierre Bourgeois", "Anne-Marie Le Sourd", "Anne Danckaert", "Mireille Lafage", "Christophe Préhaud", "Monique Lafon"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1000315.g006", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_RABV_8211_induced_NBs_exhibit_some_characteristics_of_aggresomes_/578115", "title"=>"RABV–induced NBs exhibit some characteristics of aggresomes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-02-27 02:15:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/907140"], "description"=>"<p>Co-immunostaining of TLR3 (Ab sc-Q18, green) with late (A) and early (B) endosomal compartments using anti-CD63 and anti-EEA1 Ab (red), respectively, in non-infected (NI) (A: left panels, B: upper panels) and RABV-infected (A: right panels ; B: lower panels) Ntera-2clD/1cells. Nuclei are stained with Hoechst. TLR3 colocalises with CD63 in NI (A, Merge left, arrow) and in RABV–infected cells (A, Merge right, arrow). TLR3 protein additionally forms perinuclear aggregates that do not contain endosomal markers (A and B, arrowheads). Images were acquired using a Zeiss LSM 510 META confocal microscope. Projection of 8–10 confocal images is shown. Bars = 10 µm. (C) Colocalisation of TLR3 with endosomal markers: correlation diagrams and Pearson's correlation coefficients (Rcoloc) are shown: TLR3 (Y axis) with either EEA1 (1) or CD63 (2 and 3) (X axis) are shown for NI (1–2) and RABV–infected cells (3). TLR3 shows very little association with the early endosomal compartment (1), but is strongly associated with the late endosomal marker in the absence of infection (2). Colocalisation with the late endosomal marker decreases following RABV infection (3).</p>", "links"=>[], "tags"=>["colocalises", "endosomal", "compartment", "non-infected", "cells", "relocates", "perinuclear", "aggregates", "rabv"], "article_id"=>577583, "categories"=>["Immunology", "Medicine", "Infectious Diseases"], "users"=>["Pauline Ménager", "Pascal Roux", "Françoise Mégret", "Jean-Pierre Bourgeois", "Anne-Marie Le Sourd", "Anne Danckaert", "Mireille Lafage", "Christophe Préhaud", "Monique Lafon"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1000315.g002", "stats"=>{"downloads"=>2, "page_views"=>109, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_TLR3_partially_colocalises_with_the_endosomal_compartment_of_non_infected_and_RABV_8211_infected_Ntera_2clD_1_cells_and_relocates_into_perinuclear_aggregates_after_RABV_infection_/577583", "title"=>"TLR3 partially colocalises with the endosomal compartment of non-infected and RABV–infected Ntera-2clD/1 cells and relocates into perinuclear aggregates after RABV infection.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-02-27 02:06:23"}
  • {"files"=>["https://ndownloader.figshare.com/files/907884"], "description"=>"<p>Hek293A cells were nucleofected (Q-001 Amaxa Program) with Emerald-GFP-plasmids encoding specific miRNA for TLR3 (miTLR3) or control miRNA (miNEG). 24 h post-nucleofection cells were infected or not with RABV. (A) Efficiency of silencing was assayed at transcriptional level by quantitative PCR (left panel) and at protein level by cytofluorimetry (right panel). TLR3 mRNA levels in miTLR3–treated cells were 60% lower than in miNEG cells. Cytofluorimetry analysis showed that TLR3 levels (shift to the left) in miTLR3–treated cells were lower than in miNEG cells. The values are representative of at least 3 experiments. (B) TLR3 silencing decreases viral multiplication. Control cells (miNEG) and TLR3–silenced cells (miTLR3) were assessed for viral genomic material (left panel, Q-PCR) and RABV protein N levels by flow cytometry (right panel). RABV transcription was decreased by 80% after silencing panel and the percentage of cells producing N was reduced following TLR3 silencing. (C) The absence of NBs was demonstrated by immunofluorescence. TLR3–silenced cells were immunostained with anti–TLR3 (Sc-Q18) (red) and anti-viral N protein Ab (blue). Plasmid encodes emerald-GFP (green). NBs were detected in TLR3-positive cells but not in TLR3–silenced cells as observed in the miTLR3 population. Bars = 20 µm. (D) Enlarged area of C panels.</p>", "links"=>[], "tags"=>["viral"], "article_id"=>578333, "categories"=>["Immunology", "Medicine", "Infectious Diseases"], "users"=>["Pauline Ménager", "Pascal Roux", "Françoise Mégret", "Jean-Pierre Bourgeois", "Anne-Marie Le Sourd", "Anne Danckaert", "Mireille Lafage", "Christophe Préhaud", "Monique Lafon"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1000315.g008", "stats"=>{"downloads"=>3, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_TLR3_is_required_for_the_formation_of_viral_NBs_/578333", "title"=>"TLR3 is required for the formation of viral NBs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-02-27 02:18:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/907394"], "description"=>"<p>They contain viral N and P, but not G. (A) Immunostaining of RABV P protein (P) and N protein (N) using specific Ab shows the colocalisation of the two proteins within the NBs (merge+nuclei) (B) RABV–induced aggregates (NC, green) do not contain RABV G protein (G, red). Bar = 10 µm. (C–D) Ntera-2clD/1 cells were infected with RABV, fixed with PFA, and stained with an Ab directed against NC 12, 24, and 48 h pi. (C) Small perinuclear aggregates are detected as early as 12 h pi and their size increases with time. (D, left panel) Size of aggregates increase as the infection progress from a 1 µm diameter 12 h pi up to 3.0 µm 48 h pi. In this experiment, viral NB diameters were measured manually using the Leica FW 4000 software. Graph represents means with SEM. (D, right panel) 24 h after pi majority of cells contains 1–3 NBs. Viral NB were quantified by Acapella Software.</p>", "links"=>[], "tags"=>["inclusion", "bodies", "correspond", "negri"], "article_id"=>577838, "categories"=>["Immunology", "Medicine", "Infectious Diseases"], "users"=>["Pauline Ménager", "Pascal Roux", "Françoise Mégret", "Jean-Pierre Bourgeois", "Anne-Marie Le Sourd", "Anne Danckaert", "Mireille Lafage", "Christophe Préhaud", "Monique Lafon"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1000315.g004", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_RABV_8211_induced_inclusion_bodies_correspond_to_Negri_Bodies_NBs_/577838", "title"=>"RABV–induced inclusion bodies correspond to Negri Bodies (NBs).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-02-27 02:10:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/448797", "https://ndownloader.figshare.com/files/448830", "https://ndownloader.figshare.com/files/448857", "https://ndownloader.figshare.com/files/448893"], "description"=>"<div><p>Human neurons express the innate immune response receptor, Toll-like receptor 3 (TLR3). TLR3 levels are increased in pathological conditions such as brain virus infection. Here, we further investigated the production, cellular localisation, and function of neuronal TLR3 during neuronotropic rabies virus (RABV) infection in human neuronal cells. Following RABV infection, TLR3 is not only present in endosomes, as observed in the absence of infection, but also in detergent-resistant perinuclear inclusion bodies. As well as TLR3, these inclusion bodies contain the viral genome and viral proteins (N and P, but not G). The size and composition of inclusion bodies and the absence of a surrounding membrane, as shown by electron microscopy, suggest they correspond to the previously described Negri Bodies (NBs). NBs are not formed in the absence of TLR3, and TLR3<sup>−/−</sup> mice—in which brain tissue was less severely infected—had a better survival rate than WT mice. These observations demonstrate that TLR3 is a major molecule involved in the spatial arrangement of RABV–induced NBs and viral replication. This study shows how viruses can exploit cellular proteins and compartmentalisation for their own benefit.</p></div>", "links"=>[], "tags"=>["toll-like", "receptor", "plays", "rabies", "negri", "bodies"], "article_id"=>148440, "categories"=>["Immunology", "Medicine", "Cancer"], "users"=>["Pauline Ménager", "Pascal Roux", "Françoise Mégret", "Jean-Pierre Bourgeois", "Anne-Marie Le Sourd", "Anne Danckaert", "Mireille Lafage", "Christophe Préhaud", "Monique Lafon"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1000315.s001", "https://dx.doi.org/10.1371/journal.ppat.1000315.s002", "https://dx.doi.org/10.1371/journal.ppat.1000315.s003", "https://dx.doi.org/10.1371/journal.ppat.1000315.s004"], "stats"=>{"downloads"=>4, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Toll_Like_Receptor_3_TLR3_Plays_a_Major_Role_in_the_Formation_of_Rabies_Virus_Negri_Bodies/148440", "title"=>"Toll-Like Receptor 3 (TLR3) Plays a Major Role in the Formation of Rabies Virus Negri Bodies", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2009-02-27 02:20:40"}
  • {"files"=>["https://ndownloader.figshare.com/files/907540"], "description"=>"<p>Aggregates contain RABV genomic material. RABV–infected (A–C) and non-infected (D) BSR cells were incubated with (A, C, D) or without (B) fluorescein-conjugated RNA probes specific for the viral RABV genome. Both fluorescent (upper panels) and transmission images (lower panels) were shown for each condition. (A) Genomic material was detected in the discrete aggregates (arrows) located around the nuclei (N) of RABV–infected cells. (B) No fluorescence is seen in RABV–infected cells in the absence of RNA probes. These pictures were acquired with a Leica DM5000B fluorescence microscope. (C) Detail of a RABV–infected single cell with the anti-genomic probe (confocal stack). (D) No fluorescence was detected in non-infected cells incubated with the fluorescein-conjugated RNA probes. Bars (A–D) = 10 µm. (E and F) Neuroblastoma SK-N-SH cells were infected for 48 h with RABV, fixed and prepared for electron microscopy analysis. (E) Electron microscopy of a section showing that aggregates are located near the nucleus (N) surrounded by mitochondria (M) and rough endoplasmic reticulum (rER). Aggregates are not limited by a membrane. B.w = base of culture well. C.m = culture medium. (F) Viral inclusions are seen close to the sites of viral assembly. Nests of virus particles (arrow) are located close to viral NBs and rER. Bars = 2 µm.</p>", "links"=>[], "tags"=>["viral", "genomic", "suggesting", "specialized", "sites"], "article_id"=>577989, "categories"=>["Immunology", "Medicine", "Infectious Diseases"], "users"=>["Pauline Ménager", "Pascal Roux", "Françoise Mégret", "Jean-Pierre Bourgeois", "Anne-Marie Le Sourd", "Anne Danckaert", "Mireille Lafage", "Christophe Préhaud", "Monique Lafon"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1000315.g005", "stats"=>{"downloads"=>2, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_NBs_contain_viral_genomic_material_suggesting_they_are_specialized_sites_for_viral_multiplication_/577989", "title"=>"NBs contain viral genomic material, suggesting they are specialized sites for viral multiplication.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-02-27 02:13:09"}

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Relative Metric

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