Novel decay dynamics revealed for virus-mediated drug activation in cytomegalovirus infection
Publication Date
April 13, 2017
Authors
Jessica Rose, Vincent C. Emery, Deepali Kumar, Anders Asberg, et al
Volume
13
Issue
4
Pages
e1006299
DOI
https://dx.plos.org/10.1371/journal.ppat.1006299
Publisher URL
http://journals.plos.org/plospathogens/article?id=10.1371%2Fjournal.ppat.1006299
Scopus
85018315156
Mendeley
http://www.mendeley.com/research/novel-decay-dynamics-revealed-virusmediated-drug-activation-cytomegalovirus-infection
Events
Loading … Spinner

Mendeley | Further Information

{"title"=>"Novel decay dynamics revealed for virus-mediated drug activation in cytomegalovirus infection", "type"=>"journal", "authors"=>[{"first_name"=>"Jessica", "last_name"=>"Rose", "scopus_author_id"=>"57074940400"}, {"first_name"=>"Vincent C.", "last_name"=>"Emery", "scopus_author_id"=>"7102404974"}, {"first_name"=>"Deepali", "last_name"=>"Kumar", "scopus_author_id"=>"7402293996"}, {"first_name"=>"Anders", "last_name"=>"Asberg", "scopus_author_id"=>"7005233234"}, {"first_name"=>"Anders", "last_name"=>"Hartmann", "scopus_author_id"=>"55204304800"}, {"first_name"=>"Alan G.", "last_name"=>"Jardine", "scopus_author_id"=>"34569675200"}, {"first_name"=>"Angelo A.", "last_name"=>"Bignamini", "scopus_author_id"=>"7004559940"}, {"first_name"=>"Atul", "last_name"=>"Humar", "scopus_author_id"=>"7006190495"}, {"first_name"=>"Avidan U.", "last_name"=>"Neumann", "scopus_author_id"=>"7201740253"}], "year"=>2017, "source"=>"PLoS Pathogens", "identifiers"=>{"isbn"=>"1111111111", "doi"=>"10.1371/journal.ppat.1006299", "pui"=>"615827182", "issn"=>"15537374", "sgr"=>"85018315156", "scopus"=>"2-s2.0-85018315156"}, "id"=>"35e1f63b-4172-32f0-855a-55ce42b60c08", "abstract"=>"Human cytomegalovirus (CMV) infection is a substantial cause of morbidity and mortality in immunocompromised hosts and globally is one of the most important congenital infections. The nucleoside analogue ganciclovir (GCV), which requires initial phosphorylation by the viral UL97 kinase, is the mainstay for treatment. To date, CMV decay kinetics during GCV therapy have not been extensively investigated and its clinical implications not fully appreciated. We measured CMV DNA levels in the blood of 92 solid organ transplant recipients with CMV disease over the initial 21 days of ganciclovir therapy and identified four distinct decay patterns, including a new pattern exhibiting a transient viral rebound (Hump) following initial decline. Since current viral dynamics models were unable to account for this Hump profile, we developed a novel multi-level model, which includes the intracellular role of UL97 in the continued activation of ganciclovir, that successfully described all the decline patterns observed. Fitting the data allowed us to estimate ganciclovir effectiveness in vivo (mean 92%), infected cell half-life (mean 0.7 days), and other viral dynamics parameters that determine which of the four kinetic patterns will ensue. An important clinical implication of our results is that the virological efficacy of GCV operates over a broad dose range. The model also raises the possibility that GCV can drive replication to a new lower steady state but ultimately cannot fully eradicate it. This model is likely to be generalizable to other anti-CMV nucleoside analogs that require activation by viral enzymes such as UL97 or its homologues. Copyright � 2017 Rose et al.", "link"=>"http://www.mendeley.com/research/novel-decay-dynamics-revealed-virusmediated-drug-activation-cytomegalovirus-infection", "reader_count"=>4, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Student > Ph. D. Student"=>1, "Other"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Student > Ph. D. Student"=>1, "Other"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Medicine and Dentistry"=>2, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Unspecified"=>{"Unspecified"=>1}}, "group_count"=>1}

Scopus | Further Information

{"@_fa"=>"true", "link"=>[{"@_fa"=>"true", "@ref"=>"self", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/85018315156"}, {"@_fa"=>"true", "@ref"=>"author-affiliation", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/85018315156?field=author,affiliation"}, {"@_fa"=>"true", "@ref"=>"scopus", "@href"=>"https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85018315156&origin=inward"}, {"@_fa"=>"true", "@ref"=>"scopus-citedby", "@href"=>"https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85018315156&origin=inward"}], "prism:url"=>"https://api.elsevier.com/content/abstract/scopus_id/85018315156", "dc:identifier"=>"SCOPUS_ID:85018315156", "eid"=>"2-s2.0-85018315156", "dc:title"=>"Novel decay dynamics revealed for virus-mediated drug activation in cytomegalovirus infection", "dc:creator"=>"Rose J.", "prism:publicationName"=>"PLoS Pathogens", "prism:issn"=>"15537366", "prism:eIssn"=>"15537374", "prism:volume"=>"13", "prism:issueIdentifier"=>"4", "prism:pageRange"=>nil, "prism:coverDate"=>"2017-04-01", "prism:coverDisplayDate"=>"April 2017", "prism:doi"=>"10.1371/journal.ppat.1006299", "citedby-count"=>"2", "affiliation"=>[{"@_fa"=>"true", "affilname"=>"The Ruth and Bruce Rappaport Faculty of Medicine", "affiliation-city"=>"Haifa", "affiliation-country"=>"Israel"}, {"@_fa"=>"true", "affilname"=>"Bar-Ilan University", "affiliation-city"=>"Ramat Gan", "affiliation-country"=>"Israel"}], "pubmed-id"=>"28406982", "prism:aggregationType"=>"Journal", "subtype"=>"ar", "subtypeDescription"=>"Article", "article-number"=>"e1006299", "source-id"=>"4000151809", "openaccess"=>"1", "openaccessFlag"=>true}

Counter

  • {"month"=>"4", "year"=>"2017", "pdf_views"=>"89", "xml_views"=>"12", "html_views"=>"1558"}
  • {"month"=>"5", "year"=>"2017", "pdf_views"=>"75", "xml_views"=>"13", "html_views"=>"300"}
  • {"month"=>"6", "year"=>"2017", "pdf_views"=>"21", "xml_views"=>"1", "html_views"=>"91"}
  • {"month"=>"7", "year"=>"2017", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"64"}
  • {"month"=>"8", "year"=>"2017", "pdf_views"=>"26", "xml_views"=>"0", "html_views"=>"41"}
  • {"month"=>"9", "year"=>"2017", "pdf_views"=>"7", "xml_views"=>"2", "html_views"=>"36"}
  • {"month"=>"10", "year"=>"2017", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"28"}
  • {"month"=>"11", "year"=>"2017", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"41"}
  • {"month"=>"12", "year"=>"2017", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"35"}
  • {"month"=>"1", "year"=>"2018", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"35"}
  • {"month"=>"2", "year"=>"2018", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"20"}
  • {"month"=>"3", "year"=>"2018", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"18"}
  • {"month"=>"4", "year"=>"2018", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"20"}
  • {"month"=>"5", "year"=>"2018", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"33"}
  • {"month"=>"6", "year"=>"2018", "pdf_views"=>"10", "xml_views"=>"1", "html_views"=>"22"}
  • {"month"=>"7", "year"=>"2018", "pdf_views"=>"7", "xml_views"=>"4", "html_views"=>"11"}
  • {"month"=>"8", "year"=>"2018", "pdf_views"=>"4", "xml_views"=>"1", "html_views"=>"11"}
  • {"month"=>"9", "year"=>"2018", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"16"}
  • {"month"=>"10", "year"=>"2018", "pdf_views"=>"4", "xml_views"=>"1", "html_views"=>"10"}
  • {"month"=>"11", "year"=>"2018", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"4"}
  • {"month"=>"12", "year"=>"2018", "pdf_views"=>"20", "xml_views"=>"0", "html_views"=>"2"}
  • {"month"=>"1", "year"=>"2019", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"8"}
  • {"month"=>"2", "year"=>"2019", "pdf_views"=>"14", "xml_views"=>"0", "html_views"=>"14"}
  • {"month"=>"3", "year"=>"2019", "pdf_views"=>"8", "xml_views"=>"1", "html_views"=>"12"}
  • {"month"=>"4", "year"=>"2019", "pdf_views"=>"6", "xml_views"=>"1", "html_views"=>"6"}
  • {"month"=>"5", "year"=>"2019", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"15"}
  • {"month"=>"6", "year"=>"2019", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"13"}
  • {"month"=>"7", "year"=>"2019", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"2"}
  • {"month"=>"8", "year"=>"2019", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"12"}
  • {"month"=>"9", "year"=>"2019", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"13"}
  • {"month"=>"10", "year"=>"2019", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"8"}
  • {"month"=>"11", "year"=>"2019", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"12"}
  • {"month"=>"12", "year"=>"2019", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"7"}

PMC Usage Stats

  • {"unique-ip"=>"34", "full-text"=>"28", "pdf"=>"16", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"5"}
  • {"unique-ip"=>"19", "full-text"=>"19", "pdf"=>"10", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2017", "month"=>"6"}
  • {"unique-ip"=>"13", "full-text"=>"48", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"7"}
  • {"unique-ip"=>"9", "full-text"=>"11", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"8"}
  • {"unique-ip"=>"16", "full-text"=>"13", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"9"}
  • {"unique-ip"=>"13", "full-text"=>"14", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"10"}
  • {"unique-ip"=>"6", "full-text"=>"6", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"11"}
  • {"unique-ip"=>"7", "full-text"=>"6", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"12"}
  • {"unique-ip"=>"15", "full-text"=>"15", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"14", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"1"}
  • {"unique-ip"=>"1", "full-text"=>"1", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"2"}
  • {"unique-ip"=>"9", "full-text"=>"8", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2018", "month"=>"3"}
  • {"unique-ip"=>"7", "full-text"=>"12", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"3", "cited-by"=>"1", "year"=>"2019", "month"=>"1"}
  • {"unique-ip"=>"12", "full-text"=>"15", "pdf"=>"9", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2018", "month"=>"5"}
  • {"unique-ip"=>"7", "full-text"=>"10", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"4"}
  • {"unique-ip"=>"6", "full-text"=>"6", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2018", "month"=>"7"}
  • {"unique-ip"=>"6", "full-text"=>"6", "pdf"=>"7", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"6"}
  • {"unique-ip"=>"7", "full-text"=>"10", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"8"}
  • {"unique-ip"=>"5", "full-text"=>"9", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"9"}
  • {"unique-ip"=>"4", "full-text"=>"13", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
  • {"unique-ip"=>"7", "full-text"=>"14", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
  • {"unique-ip"=>"5", "full-text"=>"9", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"7", "full-text"=>"16", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"8", "full-text"=>"10", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"4", "full-text"=>"11", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"11", "full-text"=>"17", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}
  • {"unique-ip"=>"6", "full-text"=>"9", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"8"}
  • {"unique-ip"=>"5", "full-text"=>"11", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"9"}
  • {"unique-ip"=>"6", "full-text"=>"10", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2019", "month"=>"10"}
Loading … Spinner
There are currently no alerts