Mendeley | Further Information

{"title"=>"Novel mechanisms to inhibit HIV reservoir seeding using Jak inhibitors", "type"=>"journal", "authors"=>[{"first_name"=>"Christina", "last_name"=>"Gavegnano", "scopus_author_id"=>"35145674200"}, {"first_name"=>"Jessica H.", "last_name"=>"Brehm", "scopus_author_id"=>"17343449600"}, {"first_name"=>"Franck P.", "last_name"=>"Dupuy", "scopus_author_id"=>"8940648000"}, {"first_name"=>"Aarthi", "last_name"=>"Talla", "scopus_author_id"=>"57045855100"}, {"first_name"=>"Susan Pereira", "last_name"=>"Ribeiro", "scopus_author_id"=>"24492453800"}, {"first_name"=>"Deanna A.", "last_name"=>"Kulpa", "scopus_author_id"=>"6507075670"}, {"first_name"=>"Cheryl", "last_name"=>"Cameron", "scopus_author_id"=>"57196652647"}, {"first_name"=>"Stephanie", "last_name"=>"Santos", "scopus_author_id"=>"57200141994"}, {"first_name"=>"Selwyn J.", "last_name"=>"Hurwitz", "scopus_author_id"=>"7101862038"}, {"first_name"=>"Vincent C.", "last_name"=>"Marconi", "scopus_author_id"=>"22951187600"}, {"first_name"=>"Jean Pierre", "last_name"=>"Routy", "scopus_author_id"=>"7003631689"}, {"first_name"=>"Laurent", "last_name"=>"Sabbagh", "scopus_author_id"=>"15519626600"}, {"first_name"=>"Raymond F.", "last_name"=>"Schinazi", "scopus_author_id"=>"36049673200"}, {"first_name"=>"Rafick Pierre", "last_name"=>"Sékaly", "scopus_author_id"=>"7103324485"}], "year"=>2017, "source"=>"PLoS Pathogens", "identifiers"=>{"scopus"=>"2-s2.0-85039904394", "sgr"=>"85039904394", "doi"=>"10.1371/journal.ppat.1006740", "pui"=>"620067270", "pmid"=>"29267399", "isbn"=>"1111111111", "issn"=>"15537374"}, "id"=>"8e7a4595-cb35-3347-84bc-b6add19a9d91", "abstract"=>"Despite advances in the treatment of HIV infection with ART, elucidating strategies to overcome HIV persistence, including blockade of viral reservoir establishment, maintenance, and expansion, remains a challenge. T cell homeostasis is a major driver of HIV persistence. Cytokines involved in regulating homeostasis of memory T cells, the major hub of the HIV reservoir, trigger the Jak-STAT pathway. We evaluated the ability of tofacitinib and ruxolitinib, two FDA-approved Jak inhibitors, to block seeding and maintenance of the HIV reservoir in vitro. We provide direct demonstration for involvement of the Jak-STAT pathway in HIV persistence in vivo, ex vivo, and in vitro; pSTAT5 strongly correlates with increased levels of integrated viral DNA in vivo, and in vitro Jak inhibitors reduce the frequency of CD4+ T cells harboring integrated HIV DNA. We show that Jak inhibitors block viral production from infected cells, inhibit γ-C receptor cytokine (IL-15)-induced viral reactivation from latent stores thereby preventing transmission of infectious particles to bystander activated T cells. These results show that dysregulation of the Jak-STAT pathway is associated with viral persistence in vivo, and that Jak inhibitors target key events downstream of γ-C cytokine (IL-2, IL-7 and IL-15) ligation to their receptors, impacting the magnitude of the HIV reservoir in all memory CD4 T cell subsets in vitro and ex vivo. Jak inhibitors represent a therapeutic modality to prevent key events of T cell activation that regulate HIV persistence and together, specific, potent blockade of these events may be integrated to future curative strategies.", "link"=>"http://www.mendeley.com/research/novel-mechanisms-inhibit-hiv-reservoir-seeding-using-jak-inhibitors", "reader_count"=>13, "reader_count_by_academic_status"=>{"Librarian"=>1, "Student > Doctoral Student"=>2, "Researcher"=>3, "Student > Ph. D. Student"=>3, "Student > Bachelor"=>2, "Student > Master"=>1, "Unspecified"=>1}, "reader_count_by_user_role"=>{"Librarian"=>1, "Student > Doctoral Student"=>2, "Researcher"=>3, "Student > Ph. D. Student"=>3, "Student > Bachelor"=>2, "Student > Master"=>1, "Unspecified"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>2, "Agricultural and Biological Sciences"=>5, "Arts and Humanities"=>1, "Immunology and Microbiology"=>3}, "reader_count_by_subdiscipline"=>{"Immunology and Microbiology"=>{"Immunology and Microbiology"=>3}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>5}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>2}, "Arts and Humanities"=>{"Arts and Humanities"=>1}}, "group_count"=>1}

CrossRef

• http://doi.org/10.1128/JVI.00856-20
• http://doi.org/10.1186/s12974-019-1565-6
• http://doi.org/10.1097/COH.0000000000000609
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• http://doi.org/10.1016/j.molmed.2020.06.007
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• http://doi.org/10.1073/pnas.1806695115
• http://doi.org/10.1007/s11904-020-00496-0

Scopus | Further Information

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• {"unique-ip"=>"18", "full-text"=>"14", "pdf"=>"11", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"12", "supp-data"=>"7", "cited-by"=>"0", "year"=>"2019", "month"=>"9"}
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• {"unique-ip"=>"20", "full-text"=>"16", "pdf"=>"8", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"41", "cited-by"=>"0", "year"=>"2019", "month"=>"12"}
• {"unique-ip"=>"23", "full-text"=>"22", "pdf"=>"6", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"85", "cited-by"=>"0", "year"=>"2020", "month"=>"2"}
• {"unique-ip"=>"21", "full-text"=>"24", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"9", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2020", "month"=>"3"}
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• {"unique-ip"=>"18", "full-text"=>"25", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"5"}
• {"unique-ip"=>"28", "full-text"=>"24", "pdf"=>"11", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"12", "cited-by"=>"0", "year"=>"2020", "month"=>"6"}
• {"unique-ip"=>"7", "full-text"=>"7", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"7"}
• {"unique-ip"=>"12", "full-text"=>"15", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"8"}
• {"unique-ip"=>"16", "full-text"=>"14", "pdf"=>"10", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2020", "month"=>"9"}
• {"unique-ip"=>"11", "full-text"=>"9", "pdf"=>"7", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2020", "month"=>"10"}
• {"unique-ip"=>"12", "full-text"=>"10", "pdf"=>"6", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"11"}
• {"unique-ip"=>"7", "full-text"=>"7", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"12"}

F1000Prime