Interferon Impedes an Early Step of Hepatitis Delta Virus Infection
Publication Date
July 19, 2011
Journal
PLOS ONE
Authors
Ziying Han, Shoko Nogusa, Emmanuelle Nicolas, Siddharth Balachandran, et al
Volume
6
Issue
7
Pages
e22415
DOI
https://dx.plos.org/10.1371/journal.pone.0022415
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0022415
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/21811602
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3139649
Europe PMC
http://europepmc.org/abstract/MED/21811602
Web of Science
000292929500060
Scopus
79960442858
Mendeley
http://www.mendeley.com/research/interferon-impedes-early-step-hepatitis-delta-virus-infection
Events
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Mendeley | Further Information

{"title"=>"Interferon impedes an early step of hepatitis delta virus infection", "type"=>"journal", "authors"=>[{"first_name"=>"Ziying", "last_name"=>"Han", "scopus_author_id"=>"7402859100"}, {"first_name"=>"Shoko", "last_name"=>"Nogusa", "scopus_author_id"=>"8606232000"}, {"first_name"=>"Emmanuelle", "last_name"=>"Nicolas", "scopus_author_id"=>"7005638673"}, {"first_name"=>"Siddharth", "last_name"=>"Balachandran", "scopus_author_id"=>"35595842300"}, {"first_name"=>"John", "last_name"=>"Taylor", "scopus_author_id"=>"55574205239"}], "year"=>2011, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"79960442858", "doi"=>"10.1371/journal.pone.0022415", "pui"=>"362161276", "pmid"=>"21811602", "scopus"=>"2-s2.0-79960442858", "issn"=>"19326203", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)"}, "id"=>"5d08e9f8-2155-3516-ae1c-fb72be300a2a", "abstract"=>"Hepatitis delta virus (HDV) infects hepatocytes, the major cell type of the liver. Infection of the liver may be either transient or chronic. The prognosis for patients with chronic HDV infection is poor, with a high risk of cirrhosis and hepatocellular carcinoma. The best antiviral therapy is weekly administration for at least one year of high doses of interferon alpha. This efficacy of interferon therapy has been puzzling in that HDV replication in transfected cell lines is reported as insensitive to administration of interferon alpha or gamma. Similarly, this study shows that even when an interferon response was induced by transfection of poly(IC) into a cell line, HDV RNA accumulation was only modestly inhibited. However, when the HDV replication was initiated by infection of primary human hepatocytes, simultaneous addition of interferons alpha or gamma at 600 units/ml, a concentration comparable to that achieved in treated patients, the subsequent HDV RNA accumulation was inhibited by at least 80%. These interferon treatments were shown to produce significant time-dependent increases of host response proteins such as for Stat-1, phosphoStat-1, Mx1/2/3 and PKR, and yet interferon pretreatment of hepatocytes did not confer an increased inhibition of HDV replication over interferon treatment at the time of (or after) infection. These and other data support the interpretation that interferon action against HDV replication can occur and is largely mediated at the level of entry into primary human hepatocytes. Thus in vivo, the success of long-term interferon therapy for chronic HDV, may likewise involve blocking HDV spread by interfering with the initiation of productive infection of naïve hepatocytes.", "link"=>"http://www.mendeley.com/research/interferon-impedes-early-step-hepatitis-delta-virus-infection", "reader_count"=>22, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Student > Doctoral Student"=>5, "Researcher"=>5, "Student > Ph. D. Student"=>3, "Student > Postgraduate"=>2, "Student > Master"=>4, "Other"=>1, "Student > Bachelor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Student > Doctoral Student"=>5, "Researcher"=>5, "Student > Ph. D. Student"=>3, "Student > Postgraduate"=>2, "Student > Master"=>4, "Other"=>1, "Student > Bachelor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>2, "Agricultural and Biological Sciences"=>8, "Medicine and Dentistry"=>8, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Psychology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>8}, "Psychology"=>{"Psychology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>8}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>2}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"Germany"=>1}, "group_count"=>2}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/755620"], "description"=>"<p>Times of addition of inhibitors are measured relative to 3-h of virus exposure. The preS1 peptide was present at 50 nM while the interferons were at 600 U/ml. All assays were performed in at least triplicate, and the data expressed relative to control hepatocytes that were not treated with inhibitors. The indicated standard error of the mean includes the errors in both the control and the treated cultures.</p>", "links"=>[], "tags"=>["replication", "inhibited", "interferons", "alpha"], "article_id"=>425993, "categories"=>["Infectious Diseases", "Immunology"], "users"=>["Ziying Han", "Shoko Nogusa", "Emmanuelle Nicolas", "Siddharth Balachandran", "John Taylor"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0022415.t001", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_HDV_replication_is_inhibited_by_application_of_interferons_alpha_or_gamma_/425993", "title"=>"HDV replication is inhibited by application of interferons alpha or gamma.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-20 16:39:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/755124"], "description"=>"<p>Panel A: 293-δAg cells in a 24-well format were transfected with the indicated amounts of poly(IC) and after 6 h induced with or without TET. At 24 h total RNA was extracted and assayed by realtime PCR for interferon-beta1. Panels B and C: As in A, but using 293-HDV cells. In B and C the assays are for interferon-beta1 and HDV RNA, respectively. The experiment was performed in triplicate. Values are expressed in arbitrary units along with the standard error of the mean which includes the errors in both the control and the treated cultures.</p>", "links"=>[], "tags"=>["293-hdv", "tet"], "article_id"=>425486, "categories"=>["Infectious Diseases", "Immunology"], "users"=>["Ziying Han", "Shoko Nogusa", "Emmanuelle Nicolas", "Siddharth Balachandran", "John Taylor"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0022415.g001", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Transfection_of_poly_IC_into_293_948_Ag_and_293_HDV_cells_with_and_without_TET_induction_/425486", "title"=>"Transfection of poly(IC) into 293-δAg and 293-HDV cells, with and without TET induction.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 16:36:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/755496"], "description"=>"<p>For HDV infections the inhibitors were present from 24 h prior to infection and during the 16 h of exposure to virus. Replication was assayed at 6 days post-infection by realtime PCR, as in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0022415#pone-0022415-g001\" target=\"_blank\">Fig. 1C</a>. The assays were performed in triplicate, and average values are expressed as a percentage relative to the untreated controls, with the indicated standard error of the mean. For the VSV infections, the interferon was only present during the 16 h of virus exposure. VSV replication was assayed at 16 h by counting GFP positive cells. The values are expressed relative to untreated controls and the errors indicate the standard deviation as the square root of the mean. Interferon-alpha concentrations are expressed here as molarities, with 600 units/ml = 0.12 nM. The preS1 peptide, like interferon-alpha, can inhibit HDV infection, but the needed molarity is 300-times more. Interferon-alpha can inhibit VSV infection but the concentration is 1,000-time less than that needed to inhibit HDV.</p>", "links"=>[], "tags"=>["hdv", "vsv", "infections", "interferon-alpha", "pres1"], "article_id"=>425865, "categories"=>["Infectious Diseases", "Immunology"], "users"=>["Ziying Han", "Shoko Nogusa", "Emmanuelle Nicolas", "Siddharth Balachandran", "John Taylor"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0022415.g004", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Dose_response_of_HDV_and_VSV_infections_to_interferon_alpha_and_preS1_peptide_/425865", "title"=>"Dose response of HDV and VSV infections to interferon-alpha and preS1 peptide.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 16:38:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/755376"], "description"=>"<p>Hepatocytes were exposed to either interferons alpha or gamma at 600 units/ml. At time points out to 24 h, as indicated, total cell protein was extracted and analyzed by immunoblot to detect the indicated host proteins. Note that after 2 hours of treatment with interferon gamma, the pSTAT1 increases but not the total STAT1; this is because only a small fraction of the total STAT1 undergoes phosphorylation.</p>", "links"=>[], "tags"=>["induction", "interferons", "alpha", "gamma", "innate", "proteins"], "article_id"=>425746, "categories"=>["Infectious Diseases", "Immunology"], "users"=>["Ziying Han", "Shoko Nogusa", "Emmanuelle Nicolas", "Siddharth Balachandran", "John Taylor"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0022415.g003", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Time_dependent_induction_by_interferons_alpha_and_gamma_of_innate_immune_response_proteins_in_primary_hepatocytes_/425746", "title"=>"Time-dependent induction by interferons alpha and gamma of innate immune response proteins in primary hepatocytes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 16:38:11"}
  • {"files"=>["https://ndownloader.figshare.com/files/755229"], "description"=>"<p>For the five time-lines shown the open box indicates the period of HDV exposure and the shaded box the exposure to inhibitor. The effects on HDV replication of such treatments with three different inhibitors are summarized in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0022415#pone-0022415-t001\" target=\"_blank\">Table 1</a>.</p>", "links"=>[], "tags"=>["time-lines", "hepatocytes", "hdv"], "article_id"=>425599, "categories"=>["Infectious Diseases", "Immunology"], "users"=>["Ziying Han", "Shoko Nogusa", "Emmanuelle Nicolas", "Siddharth Balachandran", "John Taylor"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0022415.g002", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Representation_of_time_lines_for_exposure_of_primary_hepatocytes_to_HDV_and_potential_inhibitors_/425599", "title"=>"Representation of time-lines for exposure of primary hepatocytes to HDV and potential inhibitors.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 16:37:22"}

PMC Usage Stats | Further Information

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Relative Metric

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