Rapid Dissemination of SIV Follows Multisite Entry after Rectal Inoculation
Publication Date
May 09, 2011
Journal
PLOS ONE
Authors
Patricia Ribeiro Dos Santos, Magali Rancez, Jean Luc Prétet, Alice Michel Salzat, et al
Volume
6
Issue
5
Pages
e19493
DOI
https://dx.plos.org/10.1371/journal.pone.0019493
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0019493
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/21573012
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3090405
Europe PMC
http://europepmc.org/abstract/MED/21573012
Web of Science
000290386800016
Scopus
79955831984
Mendeley
http://www.mendeley.com/research/rapid-dissemination-siv-follows-multisite-entry-after-rectal-inoculation
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Mendeley | Further Information

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Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/389600", "https://ndownloader.figshare.com/files/389613", "https://ndownloader.figshare.com/files/389619", "https://ndownloader.figshare.com/files/389635", "https://ndownloader.figshare.com/files/389643", "https://ndownloader.figshare.com/files/389649", "https://ndownloader.figshare.com/files/389662"], "description"=>"<div><p>Receptive ano-rectal intercourse is a major cause of HIV infection in men having sex with men and in heterosexuals. Current knowledge of the mechanisms of entry and dissemination during HIV rectal transmission is scarce and does not allow the development of preventive strategies. We investigated the early steps of rectal infection in rhesus macaques inoculated with the pathogenic isolate SIVmac251 and necropsied four hours to nine days later. All macaques were positive for SIV. Control macaques inoculated with heat-inactivated virus were consistently negative for SIV. SIV DNA was detected in the rectum as early as four hours post infection by nested PCR for <em>gag</em> in many laser-microdissected samples of lymphoid aggregates and lamina propria but never in follicle-associated epithelium. Scarce SIV antigen positive cells were observed by immunohistofluorescence in the rectum, among intraepithelial and lamina propria cells as well as in clusters in lymphoid aggregates, four hours post infection and onwards. These cells were T cells and non-T cells that were not epithelial cells, CD68<sup>+</sup> macrophages, DC-SIGN<sup>+</sup> cells or fascin<sup>+</sup> dendritic cells. DC-SIGN<sup>+</sup> cells carried infectious virus. Detection of <em>Env</em> singly spliced mRNA in the mucosa by nested RT-PCR indicated ongoing viral replication. Strikingly, four hours post infection colic lymph nodes were also infected in all macaques as either SIV DNA or infectious virus was recovered. Rapid SIV entry and dissemination is consistent with trans-epithelial transport. Virions appear to cross the follicle-associated epithelium, and also the digestive epithelium. Viral replication could however be more efficient in lymphoid aggregates. The initial sequence of events differs from both vaginal and oral infections, which implies that prevention strategies for rectal transmission will have to be specific. Microbicides will need to protect both digestive and follicle-associated epithelia. Vaccines will need to induce immunity in lymph nodes as well as in the rectum.</p> </div>", "links"=>[], "tags"=>["dissemination", "siv", "follows", "multisite", "rectal", "inoculation"], "article_id"=>136932, "categories"=>["Cancer", "Microbiology"], "users"=>["Patricia Ribeiro dos Santos", "Magali Rancez", "Jean-Luc Prétet", "Alice Michel-Salzat", "Valérie Messent", "Anna Bogdanova", "Anne Couëdel-Courteille", "Evelyne Souil", "Rémi Cheynier", "Cécile Butor"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0019493.s001", "https://dx.doi.org/10.1371/journal.pone.0019493.s002", "https://dx.doi.org/10.1371/journal.pone.0019493.s003", "https://dx.doi.org/10.1371/journal.pone.0019493.s004", "https://dx.doi.org/10.1371/journal.pone.0019493.s005", "https://dx.doi.org/10.1371/journal.pone.0019493.s006", "https://dx.doi.org/10.1371/journal.pone.0019493.s007"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Rapid_Dissemination_of_SIV_Follows_Multisite_Entry_after_Rectal_Inoculation/136932", "title"=>"Rapid Dissemination of SIV Follows Multisite Entry after Rectal Inoculation", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2011-05-09 01:55:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/776409"], "description"=>"<p>Serial paraffin sections of R-H4.1 (sacrificed four hours pi; A and B) and R-H16.2 (sacrificed sixteen hours pi; C and D) were labeled by IHF for gp130 (Alexa-546, A and C), CD3 (TRITC, B and D) or fascin (Alexa-488, B and D) and nuclei were stained with DAPI (A–D). CR, crypt; LP, lamina propria; RL, rectal lumen. Arrows on serial sections point to intraepithelial T lymphocytes positive for SIV antigens. Cell-associated virus in the epithelial cell fraction was assayed by co-culture of cells isolated from the rectum. Results are expressed as TCID<sub>50</sub> per million cells. The viral load does not increase over the first four days of infection; + the TCID<sub>50</sub> could not be calculated due to small number of wells positive for SIV antigen (E).</p>", "links"=>[], "tags"=>["rectal", "epithelium"], "article_id"=>446772, "categories"=>["Microbiology", "Virology", "Infectious Diseases"], "users"=>["Patricia Ribeiro dos Santos", "Magali Rancez", "Jean-Luc Prétet", "Alice Michel-Salzat", "Valérie Messent", "Anna Bogdanova", "Anne Couëdel-Courteille", "Evelyne Souil", "Rémi Cheynier", "Cécile Butor"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0019493.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_SIV_is_present_in_the_rectal_epithelium_as_early_as_four_hours_post_infection_/446772", "title"=>"SIV is present in the rectal epithelium as early as four hours post infection.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-05-09 01:52:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/776715"], "description"=>"<p>SIV DNA is amplified by nested PCR for <i>gag</i> in most lymphoid aggregates microdissected from paraffin sections of macaques sacrificed four hours to two days pi (A); ratios indicate the number of lymphoid aggregates positive for SIV DNA relative to the total number of lymphoid aggregates tested for each macaque. Clusters of SIV-antigen positive cells are observed in paraffin embedded sections of the colo-rectal mucosa of R-H4.1 (sacrificed four hours pi; B, C and D, serial sections, dashed circle indicates the same area in the three micrographs), R-H16.1 (sacrificed sixteen hours pi; E, F enlargement of area boxed in E), and R-H24.1 (sacrificed twenty-four hours pi; G, H enlargement of area boxed in G). These clusters of SIV<sup>+</sup> cells are not observed in serial sections of R-H16.1 (I, J enlargement of area boxed in I) or R-H24.1 (K, L enlargement of area boxed in K) labeled with an irrelevant antibody of the same isotype. These clusters contain T cells but not CD68<sup>+</sup> macrophages or fascin<sup>+</sup> DCs. Sections were labeled by IHF for gp130 (Alexa-546, C), p27 (Alexa-488, E, F, G and H), CD3 (TRITC, B, D–H, K and L), fascin (Alexa-488, B), CD68 (Alexa-488, D), irrelevant antibody (Alexa-488 I–L) and nuclei were stained with DAPI (B–L). CR, crypt; LP, lamina propria; TA, T cell area of mucosal lymphoid aggregate; BF, B cell follicle.</p>", "links"=>[], "tags"=>["lymphoid", "aggregates", "colo-rectal", "mucosa"], "article_id"=>447072, "categories"=>["Microbiology", "Virology", "Infectious Diseases"], "users"=>["Patricia Ribeiro dos Santos", "Magali Rancez", "Jean-Luc Prétet", "Alice Michel-Salzat", "Valérie Messent", "Anna Bogdanova", "Anne Couëdel-Courteille", "Evelyne Souil", "Rémi Cheynier", "Cécile Butor"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0019493.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_SIV_is_present_in_lymphoid_aggregates_of_the_colo_rectal_mucosa_starting_from_four_hours_post_infection_/447072", "title"=>"SIV is present in lymphoid aggregates of the colo-rectal mucosa starting from four hours post infection.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-05-09 01:57:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/776939"], "description"=>"<p>SIV DNA is amplified by nested PCR for <i>gag</i> in some lamina propria samples microdissected from paraffin sections four to twenty four hours pi (A); ratios indicate the number of lamina propria sites positive for SIV DNA relative to the total number of lamina propria sites tested for each macaque. Serial paraffin sections of R-H16.3 (sacrificed sixteen hours pi; B and C) were labeled for p27 (Alexa-488, B) and CD3 (TRITC, C) and nuclei were stained with DAPI (B and C). CR, crypt; LP, lamina propria. Arrows on serial sections point to a lamina propria T lymphocyte positive for SIV antigen.</p>", "links"=>[], "tags"=>["colo-rectal", "lamina", "propria"], "article_id"=>447299, "categories"=>["Microbiology", "Virology", "Infectious Diseases"], "users"=>["Patricia Ribeiro dos Santos", "Magali Rancez", "Jean-Luc Prétet", "Alice Michel-Salzat", "Valérie Messent", "Anna Bogdanova", "Anne Couëdel-Courteille", "Evelyne Souil", "Rémi Cheynier", "Cécile Butor"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0019493.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_SIV_is_present_in_the_colo_rectal_lamina_propria_as_early_as_four_hours_post_infection_/447299", "title"=>"SIV is present in the colo-rectal lamina propria as early as four hours post infection.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-05-09 02:01:39"}
  • {"files"=>["https://ndownloader.figshare.com/files/777108"], "description"=>"<p>DC-SIGN<sup>+</sup> cells are observed in lymphoid aggregates of R-H4.2 (sacrificed four hours pi; A) and lamina propria of R-H4.1 (sacrificed four hours pi; C) and R-H16.3 (sacrificed sixteen hours pi; B and D). DC-SIGN<sup>+</sup> cells express only occasionally MHC-II molecules (A and B, arrows), but co-express PM-2K (C) and CD68 (D) marking them as macrophages. Frozen sections of colo-rectal mucosa were labeled for DC-SIGN (Alexa-488), CD3 (Alexa-350, A, B and D), MHC-II Mamula-DR (Alexa-546, A, B and C) or PM-2K (Alexa-350, C), CD68 (Alexa-546, D) and nuclei were stained with TO-PRO®-3 (A–D). The computer-generated merged images are shown. CR, crypt; LP, lamina propria; S, submucosal connective tissue; TA, T cell area of mucosal lymphoid aggregate; HEV, high endothelial venule.</p>", "links"=>[], "tags"=>["cells", "macrophages", "colo-rectal", "mucosa", "sixteen"], "article_id"=>447465, "categories"=>["Microbiology", "Virology", "Infectious Diseases"], "users"=>["Patricia Ribeiro dos Santos", "Magali Rancez", "Jean-Luc Prétet", "Alice Michel-Salzat", "Valérie Messent", "Anna Bogdanova", "Anne Couëdel-Courteille", "Evelyne Souil", "Rémi Cheynier", "Cécile Butor"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0019493.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_DC_SIGN_cells_are_macrophages_in_the_colo_rectal_mucosa_during_the_first_sixteen_hours_of_infection_/447465", "title"=>"DC-SIGN<sup>+</sup> cells are macrophages in the colo-rectal mucosa during the first sixteen hours of infection.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-05-09 02:04:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/777305"], "description"=>"<p>Flow cytometry analysis of cells from the rectal collagenase fraction of R-H16.3 (sacrificed sixteen hours pi) shows enrichment of DC-SIGN<sup>+</sup> cells from total cells (A) in the DC-SIGN<sup>+</sup> fraction (B) and depletion in the DC-SIGN<sup>−</sup> fraction (C); left dot plots show side scatter (SSC) versus forward scatter (FSC) and gate in which expression of DC-SIGN is analyzed; right histograms show expression of DC-SIGN and percentage of DC-SIGN<sup>+</sup> cells (bar on histogram); gray filled histogram in A corresponds to isotype control. Cell-associated viral load (expressed as TCID<sub>50</sub> per million cells; D) shows that over twenty-fold more cell-associated virus is found in the DC-SIGN enriched cell fraction than in the DC-SIGN depleted cell fraction (D).</p>", "links"=>[], "tags"=>["cells", "siv", "sixteen"], "article_id"=>447665, "categories"=>["Microbiology", "Virology", "Infectious Diseases"], "users"=>["Patricia Ribeiro dos Santos", "Magali Rancez", "Jean-Luc Prétet", "Alice Michel-Salzat", "Valérie Messent", "Anna Bogdanova", "Anne Couëdel-Courteille", "Evelyne Souil", "Rémi Cheynier", "Cécile Butor"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0019493.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Rectal_DC_SIGN_cells_can_bind_SIV_sixteen_hours_post_infection_/447665", "title"=>"Rectal DC-SIGN<sup>+</sup> cells can bind SIV sixteen hours post infection.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-05-09 02:07:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/777431"], "description"=>"<p>The presence of viral DNA was assayed on cell suspensions, on OCT-frozen samples (*) or on paraffin sections (<sup>§</sup>). +: viral DNA detected; −: no viral DNA detected. PBMC: peripheral blood mononuclear cells.</p>", "links"=>[], "tags"=>["dna", "colic", "lymph", "nodes", "peripheral", "axillary"], "article_id"=>447787, "categories"=>["Microbiology", "Virology", "Infectious Diseases"], "users"=>["Patricia Ribeiro dos Santos", "Magali Rancez", "Jean-Luc Prétet", "Alice Michel-Salzat", "Valérie Messent", "Anna Bogdanova", "Anne Couëdel-Courteille", "Evelyne Souil", "Rémi Cheynier", "Cécile Butor"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0019493.t002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Viral_DNA_is_detected_in_colic_lymph_nodes_prior_to_peripheral_blood_and_axillary_lymph_nodes_/447787", "title"=>"Viral DNA is detected in colic lymph nodes prior to peripheral blood and axillary lymph nodes.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-05-09 02:09:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/777477"], "description"=>"<p>Results are expressed as TCID<sub>50</sub> per million cells.</p><p>*at least one well was positive for SIV antigen, but the TCID<sub>50</sub> could not be calculated due to small number of SIV antigen positive wells. − no SIV antigen positive well in the experiment. PBMC: peripheral blood mononuclear cells.</p>", "links"=>[], "tags"=>["lymph", "nodes", "peripheral"], "article_id"=>447834, "categories"=>["Microbiology", "Virology", "Infectious Diseases"], "users"=>["Patricia Ribeiro dos Santos", "Magali Rancez", "Jean-Luc Prétet", "Alice Michel-Salzat", "Valérie Messent", "Anna Bogdanova", "Anne Couëdel-Courteille", "Evelyne Souil", "Rémi Cheynier", "Cécile Butor"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0019493.t003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cell_associated_virus_is_detected_rapidly_in_lymph_nodes_and_peripheral_blood_/447834", "title"=>"Cell-associated virus is detected rapidly in lymph nodes and peripheral blood.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-05-09 02:10:34"}
  • {"files"=>["https://ndownloader.figshare.com/files/777523"], "description"=>"<p>The singly spliced mRNA for the <i>Env</i> gene was detected by nested RT-PCR in the indicated tissues.</p>", "links"=>[], "tags"=>["singly", "spliced", "mrna", "earlier", "colo-rectal", "mucosa", "lymph"], "article_id"=>447881, "categories"=>["Microbiology", "Virology", "Infectious Diseases"], "users"=>["Patricia Ribeiro dos Santos", "Magali Rancez", "Jean-Luc Prétet", "Alice Michel-Salzat", "Valérie Messent", "Anna Bogdanova", "Anne Couëdel-Courteille", "Evelyne Souil", "Rémi Cheynier", "Cécile Butor"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0019493.t001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Env_singly_spliced_mRNA_is_detected_earlier_in_the_colo_rectal_mucosa_than_in_lymph_nodes_/447881", "title"=>"<i>Env</i> singly spliced mRNA is detected earlier in the colo-rectal mucosa than in lymph nodes.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-05-09 02:11:21"}

PMC Usage Stats | Further Information

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