Paucity of Intact Non-Induced Provirus with Early, Long-Term Antiretroviral Therapy of Perinatal HIV Infection
Publication Date
February 08, 2017
Authors
Kaitlin Rainwater Lovett, Carrie Ziemniak, Douglas Watson, Katherine Luzuriaga, et al
Volume
12
Issue
2
Pages
e0170548
DOI
https://dx.plos.org/10.1371/journal.pone.0170548
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0170548
Scopus
85012004465
Mendeley
http://www.mendeley.com/research/paucity-intact-noninduced-provirus-early-longterm-antiretroviral-therapy-perinatal-hiv-infection
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Mendeley | Further Information

{"title"=>"Paucity of intact non-induced provirus with early, long-Term antiretroviral therapy of perinatal HIV infection", "type"=>"journal", "authors"=>[{"first_name"=>"Kaitlin", "last_name"=>"Rainwater-Lovett", "scopus_author_id"=>"16686795300"}, {"first_name"=>"Carrie", "last_name"=>"Ziemniak", "scopus_author_id"=>"14038373500"}, {"first_name"=>"Douglas", "last_name"=>"Watson", "scopus_author_id"=>"7402906086"}, {"first_name"=>"Katherine", "last_name"=>"Luzuriaga", "scopus_author_id"=>"7003728717"}, {"first_name"=>"George", "last_name"=>"Siberry", "scopus_author_id"=>"57193359327"}, {"first_name"=>"Ann", "last_name"=>"Petru", "scopus_author_id"=>"6701791057"}, {"first_name"=>"Ya Hui", "last_name"=>"Chen", "scopus_author_id"=>"57196264533"}, {"first_name"=>"Priyanka", "last_name"=>"Uprety", "scopus_author_id"=>"35574957800"}, {"first_name"=>"Margaret", "last_name"=>"Mcmanus", "scopus_author_id"=>"7103027895"}, {"first_name"=>"Ya Chi", "last_name"=>"Ho", "scopus_author_id"=>"14066156000"}, {"first_name"=>"Susanna L.", "last_name"=>"Lamers", "scopus_author_id"=>"6602771913"}, {"first_name"=>"Deborah", "last_name"=>"Persaud", "scopus_author_id"=>"35447008400"}], "year"=>2017, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-85012004465", "sgr"=>"85012004465", "issn"=>"19326203", "doi"=>"10.1371/journal.pone.0170548", "pmid"=>"28178277", "isbn"=>"1111111111", "pui"=>"614348178"}, "id"=>"28da319f-5225-39db-b5af-486f98050a22", "abstract"=>"The latent reservoir is a major barrier to HIV eradication. Reservoir size is emerging as an important biomarker to assess the likelihood of HIV remission in the absence of antiretroviral therapy (ART) and may be reduced by earlier initiation of ART that restricts HIV spread into CD4+ T cells. Reservoir size is traditionally measured with a quantitative viral outgrowth assay (QVOA) that induces replication-competent HIV production through in vitro stimulation of resting CD4+ T cells. However, the recent identification of replication-intact, non-induced proviral genomes (NIPG) suggests the QVOA significantly underestimates (by 62-fold) latent reservoir size in chronically-infected adults. Whether formation and persistence of Intact, NIPG is thwarted by early ART initiation and long-Term virologic suppression in perinatal infection is unclear. Here, we show that the latent reservoir in 11 early treated, long-Term suppressed perinatally infected children and adolescents was not inducible by QVOA and dominated by defective, NIPG. Single genome analysis of 164 NIPG from 232 million cultured resting CD4+ T cells revealed no replication-intact, near-full length sequences. Forty-Three (26%) NIPG contained APOBEC3G-mediated hypermutation, 115 (70%) NIPG contained large internal deletions, one NIPG contained nonsense mutations and indels, and 5 (3%) NIPG were assigned as Not Evaluable due to multiple failed sequencing attempts that precluded further classification. The lack of replication competent inducible provirus and intact NIPG in this cohort indicate early, long-Term ART of perinatal infection leads to marked diminution of replication-competent HIV-1 reservoirs, creating a favorable state towards interventions aimed at virologic remission.", "link"=>"http://www.mendeley.com/research/paucity-intact-noninduced-provirus-early-longterm-antiretroviral-therapy-perinatal-hiv-infection", "reader_count"=>10, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Student > Doctoral Student"=>2, "Researcher"=>1, "Student > Ph. D. Student"=>2, "Other"=>3}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Student > Doctoral Student"=>2, "Researcher"=>1, "Student > Ph. D. Student"=>2, "Other"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>2, "Medicine and Dentistry"=>2, "Agricultural and Biological Sciences"=>3, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>3}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>2}}, "group_count"=>1}

Scopus | Further Information

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