Ganglioside and Non-ganglioside Mediated Host Responses to the Mouse Polyomavirus
Publication Date
October 16, 2015
Journal
PLOS Pathogens
Authors
John You, Samantha D. O’hara, Palanivel Velupillai, Sherry Castle, et al
Volume
11
Issue
10
Pages
e1005175
DOI
https://dx.plos.org/10.1371/journal.ppat.1005175
Publisher URL
http://journals.plos.org/plospathogens/article?id=10.1371%2Fjournal.ppat.1005175
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/26474471
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4608836
Europe PMC
http://europepmc.org/abstract/MED/26474471
Web of Science
000364462700019
Scopus
84946053985
Mendeley
http://www.mendeley.com/research/ganglioside-nonganglioside-mediated-host-responses-mouse-polyomavirus
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Mendeley | Further Information

{"title"=>"Ganglioside and Non-ganglioside Mediated Host Responses to the Mouse Polyomavirus", "type"=>"journal", "authors"=>[{"first_name"=>"John", "last_name"=>"You", "scopus_author_id"=>"7201683440"}, {"first_name"=>"Samantha D.", "last_name"=>"O’Hara", "scopus_author_id"=>"56940681500"}, {"first_name"=>"Palanivel", "last_name"=>"Velupillai", "scopus_author_id"=>"6602652135"}, {"first_name"=>"Sherry", "last_name"=>"Castle", "scopus_author_id"=>"19933699300"}, {"first_name"=>"Steven", "last_name"=>"Levery", "scopus_author_id"=>"7006104559"}, {"first_name"=>"Robert L.", "last_name"=>"Garcea", "scopus_author_id"=>"7004407503"}, {"first_name"=>"Thomas", "last_name"=>"Benjamin", "scopus_author_id"=>"7101694135"}], "year"=>2015, "source"=>"PLoS Pathogens", "identifiers"=>{"issn"=>"15537374", "sgr"=>"84946053985", "doi"=>"10.1371/journal.ppat.1005175", "pmid"=>"26474471", "scopus"=>"2-s2.0-84946053985", "pui"=>"606741106"}, "id"=>"3a2cf693-e315-3db9-8d15-3bf9c9b7839f", "abstract"=>"Gangliosides serve as receptors for internalization and infection by members of the polyomavirus family. Specificity is determined by recognition of carbohydrate moieties on the ganglioside by the major viral capsid protein VP1. For the mouse polyomavirus (MuPyV), gangliosides with terminal sialic acids in specific linkages are essential. Although many biochemical and cell culture experiments have implicated gangliosides as MuPyV receptions, the role of gangliosides in the MuPyV-infected mouse has not been investigated. Here we report results of studies using ganglioside-deficient mice and derived cell lines. Knockout mice lacking complex gangliosides were completely resistant to the cytolytic and pathogenic effects of the virus. Embryo fibroblasts from these mice were likewise resistant to infection, and supplementation with specific gangliosides restored infectibility. Although lacking receptors for viral infection, cells from ganglioside-deficient mice retained the ability to respond to the virus. Ganglioside-deficient fibroblasts responded rapidly to virus exposure with a transient induction of c-fos as an early manifestation of a mitogenic response. Additionally, splenocytes from ganglioside-deficient mice responded to MuPyV by secretion of IL-12, previously recognized as a key mediator of the innate immune response. Thus, while gangliosides are essential for infection in the animal, gangliosides are not required for mitogenic responses and innate immune responses to the virus.", "link"=>"http://www.mendeley.com/research/ganglioside-nonganglioside-mediated-host-responses-mouse-polyomavirus", "reader_count"=>9, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>1, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>1, "Student > Bachelor"=>2, "Unspecified"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>1, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>1, "Student > Bachelor"=>2, "Unspecified"=>1}, "reader_count_by_subject_area"=>{"Agricultural and Biological Sciences"=>6, "Medicine and Dentistry"=>1, "Immunology and Microbiology"=>1, "Unspecified"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>6}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"United States"=>2, "France"=>1}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2364356"], "description"=>"<p>(A) B4 and St8 knockouts in pathways of ganglioside biosynthesis. Gangliosides previously shown or shown here to function as MuPyV receptors are outlined. Modified from U. Neu and T. Stehle. (B) High performance TLC on acidic lipid fractions from kidneys of wild-type and B4 knockout mice. Lane 1 –standards for GM1, GD1a, GD1b and GT1b; lane 2 –standards for GM1 and GD1a loaded at 50% volume of lane 1; lane 3 –B4 -/-; lane 4—B4 +/-; lane 5 –B4 +/+; lane 6 –GM3 standard; lane 7 –GM2 standard; lane 8 –GD3 standard. (C) St8 KO MEFs retain a-series gangliosides. GD1a staining of WT and St8 KO MEFs show that both cell lines express GD1a. B4 KO and B4St8 KO MEFs do not express GD1a.</p>", "links"=>[], "tags"=>["mitogenic responses", "ganglioside", "il", "Embryo fibroblasts", "Mouse Polyomavirus Gangliosides", "MuPyV receptions", "virus exposure", "carbohydrate moieties", "mitogenic response", "infection", "Knockout mice", "report results", "capsid protein VP 1.", "terminal sialic acids", "mouse polyomavirus", "cell culture experiments", "polyomavirus family", "Cell lines"], "article_id"=>1579054, "categories"=>["Biological Sciences"], "users"=>["John You", "Samantha D. O’Hara", "Palanivel Velupillai", "Sherry Castle", "Steven Levery", "Robert L. Garcea", "Thomas Benjamin"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1005175.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Ganglioside_and_Non_ganglioside_Mediated_Host_Responses_to_the_Mouse_Polyomavirus_Fig_1_/1579054", "title"=>"Ganglioside and Non-ganglioside Mediated Host Responses to the Mouse Polyomavirus - Fig 1", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-10-16 04:49:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/2364357"], "description"=>"<p>A. Kaplan-Meier survival curves for wild-type and ganglioside-knockout mice. Newborn mice were inoculated intraperitoneally with ~10<sup>6</sup> PFU of the LID strain of virus and followed using death as an endpoint. B. Susceptibility of wild-type, ST8, and B4 MEFs to infection. Large T-antigen immunofluorescence of MuPyV-infected mouse embryo fibroblasts from wild-type and ganglioside-deficient mice. Cells were infected with the RA virus at an MOI of 1–2 PFU/cell.</p>", "links"=>[], "tags"=>["mitogenic responses", "ganglioside", "il", "Embryo fibroblasts", "Mouse Polyomavirus Gangliosides", "MuPyV receptions", "virus exposure", "carbohydrate moieties", "mitogenic response", "infection", "Knockout mice", "report results", "capsid protein VP 1.", "terminal sialic acids", "mouse polyomavirus", "cell culture experiments", "polyomavirus family", "Cell lines"], "article_id"=>1579055, "categories"=>["Biological Sciences"], "users"=>["John You", "Samantha D. O’Hara", "Palanivel Velupillai", "Sherry Castle", "Steven Levery", "Robert L. Garcea", "Thomas Benjamin"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1005175.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Characterization_of_St8_and_B4_KO_mice_/1579055", "title"=>"Characterization of St8 and B4 KO mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-10-16 04:49:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/2364359"], "description"=>"<p>A. GT1a and GD1b restore infectibility to B4St8 MEFs. GT1a, GD1a, and GD1b supplementation of B4St8 KO MEFs rescued RA infection in a dose responsive manner (0.5μM to 2μM). GM1 supplementation did not rescue infection of B4St8 KO MEFs. B. Virus binding to wild-type, B4St8, and GD1a-supplemented B4St8 MEFs. WT, B4St8, and GD1a-supplemented B4St8 KO MEFs were assayed for MuPyV binding by flow cytometry. Cells were starved overnight in serum free media with or without 5μM GD1a. Cells were then infected with MuPyV (NG59RA, MOI 10) at 4°C. After 30 mins at 4°C, bound virus was detected by VP1 staining. WT, B4St8, and GD1a-supplemented B4ST8 KO MEFs had a 6 to 8 fold increase in VP1 staining compared to uninfected cells (shown in grey). GD1a-supplemented B4St8 KO MEFs showed a similar VP1 binding pattern as WT MEFs and B4St8 KO MEFs showed lower levels of VP1 accumulation on the cell surface. The x-axis is VP1 staining and the y-axis is normalized cell counts, each sample contained >10,000 cells.</p>", "links"=>[], "tags"=>["mitogenic responses", "ganglioside", "il", "Embryo fibroblasts", "Mouse Polyomavirus Gangliosides", "MuPyV receptions", "virus exposure", "carbohydrate moieties", "mitogenic response", "infection", "Knockout mice", "report results", "capsid protein VP 1.", "terminal sialic acids", "mouse polyomavirus", "cell culture experiments", "polyomavirus family", "Cell lines"], "article_id"=>1579057, "categories"=>["Biological Sciences"], "users"=>["John You", "Samantha D. O’Hara", "Palanivel Velupillai", "Sherry Castle", "Steven Levery", "Robert L. Garcea", "Thomas Benjamin"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1005175.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Ganglioside_and_Non_ganglioside_Mediated_Host_Responses_to_the_Mouse_Polyomavirus_Fig_3_/1579057", "title"=>"Ganglioside and Non-ganglioside Mediated Host Responses to the Mouse Polyomavirus - Fig 3", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-10-16 04:49:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/2364361"], "description"=>"<p>Wild-type MEFs were infected with MuPyV and then fixed at the indicated times post infection (30 min, 3hrs). <b>(A)</b> Slides were stained for cell surface VP1 (red), and then permeabilized and stained for total VP1, showing both cell surface and intracellular VP1 (green). <b>(B)</b> At 30 mins post-infection line scan analysis shows that MEFs exhibit similar staining for cell surface and total VP1, indicating minimal virus internalization. <b>(C)</b> At 3 hrs post-infection line scan analysis shows that MEFs exhibit abundant intracellular VP1 staining (green only), indicating internalized virus.</p>", "links"=>[], "tags"=>["mitogenic responses", "ganglioside", "il", "Embryo fibroblasts", "Mouse Polyomavirus Gangliosides", "MuPyV receptions", "virus exposure", "carbohydrate moieties", "mitogenic response", "infection", "Knockout mice", "report results", "capsid protein VP 1.", "terminal sialic acids", "mouse polyomavirus", "cell culture experiments", "polyomavirus family", "Cell lines"], "article_id"=>1579059, "categories"=>["Biological Sciences"], "users"=>["John You", "Samantha D. O’Hara", "Palanivel Velupillai", "Sherry Castle", "Steven Levery", "Robert L. Garcea", "Thomas Benjamin"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1005175.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Virus_Internalization_in_Wild_Type_MEFs_/1579059", "title"=>"Virus Internalization in Wild-Type MEFs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-10-16 04:49:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/2364363"], "description"=>"<p>B4St8 knock out MEFs were infected with MuPyV and then fixed at the indicated times post infection (30 min, 3 hrs). <b>(A)</b> Slides were stained for cell surface VP1 (red), and then permeabilized and stained for total VP1, showing both cell surface and intracellular VP1 (green). <b>(B)</b> At 30 mins post-infection line scan analysis shows that B4St8 MEFs exhibit similar staining for cell surface and total VP1, indicating minimal virus internalization. <b>(C)</b> At 3 hrs post-infection line scan analysis shows that B4St8 KO MEFs exhibit abundant intracellular VP1 staining (green only), indicating internalized virus.</p>", "links"=>[], "tags"=>["mitogenic responses", "ganglioside", "il", "Embryo fibroblasts", "Mouse Polyomavirus Gangliosides", "MuPyV receptions", "virus exposure", "carbohydrate moieties", "mitogenic response", "infection", "Knockout mice", "report results", "capsid protein VP 1.", "terminal sialic acids", "mouse polyomavirus", "cell culture experiments", "polyomavirus family", "Cell lines"], "article_id"=>1579061, "categories"=>["Biological Sciences"], "users"=>["John You", "Samantha D. O’Hara", "Palanivel Velupillai", "Sherry Castle", "Steven Levery", "Robert L. Garcea", "Thomas Benjamin"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1005175.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Virus_Internalization_in_B4St8_KO_MEFs_/1579061", "title"=>"Virus Internalization in B4St8 KO MEFs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-10-16 04:49:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/2364364"], "description"=>"<p>Purified virus in serum-free medium was used to infect wild-type and B4St8 KO MEFs. Cell extracts were made at the indicated times post-infection and subjected to western blot analysis with anti-fos antibody.</p>", "links"=>[], "tags"=>["mitogenic responses", "ganglioside", "il", "Embryo fibroblasts", "Mouse Polyomavirus Gangliosides", "MuPyV receptions", "virus exposure", "carbohydrate moieties", "mitogenic response", "infection", "Knockout mice", "report results", "capsid protein VP 1.", "terminal sialic acids", "mouse polyomavirus", "cell culture experiments", "polyomavirus family", "Cell lines"], "article_id"=>1579062, "categories"=>["Biological Sciences"], "users"=>["John You", "Samantha D. O’Hara", "Palanivel Velupillai", "Sherry Castle", "Steven Levery", "Robert L. Garcea", "Thomas Benjamin"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1005175.g006"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Induction_of_c_fos_in_wild_type_and_B4St8_KO_MEFs_/1579062", "title"=>"Induction of c-fos in wild-type and B4St8 KO MEFs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-10-16 04:49:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/2364365"], "description"=>"<p>Susceptibility of wild-type and ganglioside deficient MEFs to small plaque and large plaque polyomavirus strains.</p>", "links"=>[], "tags"=>["mitogenic responses", "ganglioside", "il", "Embryo fibroblasts", "Mouse Polyomavirus Gangliosides", "MuPyV receptions", "virus exposure", "carbohydrate moieties", "mitogenic response", "infection", "Knockout mice", "report results", "capsid protein VP 1.", "terminal sialic acids", "mouse polyomavirus", "cell culture experiments", "polyomavirus family", "Cell lines"], "article_id"=>1579063, "categories"=>["Biological Sciences"], "users"=>["John You", "Samantha D. O’Hara", "Palanivel Velupillai", "Sherry Castle", "Steven Levery", "Robert L. Garcea", "Thomas Benjamin"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1005175.t001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Susceptibility_of_wild_type_and_ganglioside_deficient_MEFs_to_small_plaque_and_large_plaque_polyomavirus_strains_/1579063", "title"=>"Susceptibility of wild-type and ganglioside deficient MEFs to small plaque and large plaque polyomavirus strains.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-10-16 04:49:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/2364366"], "description"=>"<p>GD3 Supplementation of B4ST8 MEFs.</p>", "links"=>[], "tags"=>["mitogenic responses", "ganglioside", "il", "Embryo fibroblasts", "Mouse Polyomavirus Gangliosides", "MuPyV receptions", "virus exposure", "carbohydrate moieties", "mitogenic response", "infection", "Knockout mice", "report results", "capsid protein VP 1.", "terminal sialic acids", "mouse polyomavirus", "cell culture experiments", "polyomavirus family", "Cell lines"], "article_id"=>1579064, "categories"=>["Biological Sciences"], "users"=>["John You", "Samantha D. O’Hara", "Palanivel Velupillai", "Sherry Castle", "Steven Levery", "Robert L. Garcea", "Thomas Benjamin"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1005175.t002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_GD3_Supplementation_of_B4ST8_MEFs_/1579064", "title"=>"GD3 Supplementation of B4ST8 MEFs.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-10-16 04:49:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/2364367"], "description"=>"<p>IL-12 response to MuPyV by splenocytes in KO mice.</p>", "links"=>[], "tags"=>["mitogenic responses", "ganglioside", "il", "Embryo fibroblasts", "Mouse Polyomavirus Gangliosides", "MuPyV receptions", "virus exposure", "carbohydrate moieties", "mitogenic response", "infection", "Knockout mice", "report results", "capsid protein VP 1.", "terminal sialic acids", "mouse polyomavirus", "cell culture experiments", "polyomavirus family", "Cell lines"], "article_id"=>1579065, "categories"=>["Biological Sciences"], "users"=>["John You", "Samantha D. O’Hara", "Palanivel Velupillai", "Sherry Castle", "Steven Levery", "Robert L. Garcea", "Thomas Benjamin"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1005175.t003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_IL_12_response_to_MuPyV_by_splenocytes_in_KO_mice_/1579065", "title"=>"IL-12 response to MuPyV by splenocytes in KO mice.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-10-16 04:49:03"}

PMC Usage Stats | Further Information

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Relative Metric

{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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