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Quantitative humoral profiling of the HIV-1 proteome in elite controllers and patients with very long-term efficient antiretroviral therapy
KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab. Karolinska Inst, Sweden.
KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.ORCID iD: 0000-0002-0242-358X
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2017 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 666Article in journal (Refereed) Published
Abstract [en]

A major challenge in evaluating the success of HIV eradication approaches is the need for accurate measurement of persistent HIV during effective antiretroviral therapy (ART). Previous studies have reported that the anti-HIV antibody assay "luciferase immuno-precipitation systems (LIPS)"can distinguish HIV-infected individuals harboring different sizes of the viral reservoirs. We performed antibody profiling of HIV-1 proteomes using LIPS in viremic progressors (n = 38), elite controllers (ECs; n = 19) and patients with fully suppressive long-term antiretroviral therapy (ART) (n = 19) (mean 17 years). IgG was quantified against six HIV-1 fusion proteins: p24, gp41, RT, Tat, integrase and protease. Lower antibody levels to all six-fusion proteins were observed in long-term ART patients compared to viremics (p < 0.05). In contrast ECs had lower antibody levels only against Tat and Integrase (p < 0.05). Principal component analysis and cluster-network analysis identified that 68% (13/19) of the long-term ART patients clustered together with 26% (5/19) ECs. The remaining ECs clustered together with the viremics indicating non-homogeneity among the ECs. The low anti-HIV levels in the long-term treated patients may indicate a restricted remaining viral replication. In contrast, the higher levels in ECs suggest a continuous viral expression with a limited concomitant release of extracellular virus.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP , 2017. Vol. 7, article id 666
National Category
Nano Technology
Identifiers
URN: urn:nbn:se:kth:diva-206253DOI: 10.1038/s41598-017-00759-8ISI: 000398545400010PubMedID: 28386076Scopus ID: 2-s2.0-85018367653OAI: oai:DiVA.org:kth-206253DiVA, id: diva2:1095320
Note

QC 20170512

Available from: 2017-05-12 Created: 2017-05-12 Last updated: 2019-01-29Bibliographically approved
In thesis
1. Development of novel molecular and microfluidics tools for identification and characterization of latent HIV-1 reservoir
Open this publication in new window or tab >>Development of novel molecular and microfluidics tools for identification and characterization of latent HIV-1 reservoir
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The existence of latent HIV-1 reservoir (LR) in all HIV-1 infected patients serves as a major obstacle to completely cure HIV-1 infection. However, up to now there is still no available assay that provides an accurate measurement of the reservoir size. This thesis aims to address this challenge from different aspects with several novel technologies, using both molecular and microfluidics-based tools. To find a proper tool to identify the latent HIV-1 reservoir, in Paper I and II, LIPS assay, RNAflow, and RNAscope assay were optimized and evaluated for indirect and direct detection of latent HIV-1 reservoir. The results indicated the LIPS method might not be sufficient for latent HIV-1 reservoir detection, although it has been proposed to quantify the latent HIV-1 reservoir indirectly. Furthermore, the optimized RNAscope technique performed better than RNAflow for transcription and translation competent latent HIV-1 reservoir identification. The RNAscope was also found to be independent of the HIV-1 subtype and can be applied to patient samples at single cell level. As there are currently no available surface biomarkers for latent HIV-1 reservoir, in Paper III, transcriptomics and proteomics-based analysis method for high-throughput selection of potential biomarker were established and applied to different patient groups. Twelve membrane protein-coding genes were identified as downregulated in the patient group who were hypothesized to have lower latent reservoir. These proteins might have the potential to be used as surface biomarkers for latent HIV-1 reservoir. CD4+ T cells, monocyte/macrophages, and natural killer cells are believed to be the primary source for HIV-1 reservoirs in peripheral blood. In paper IV, a microfluidic chip was developed to simultaneously isolate these three mononuclear leukocyte cell types directly from whole blood. The microfluidic method reduces the sample volume requirement and is a promising tool for latent HIV-1 reservoir study. Together, though further improvement and clinical verification are necessary, the work in this thesis has contributed to the advancement of latent HIV-1 reservoir characterization and may facilitate future development of the latent HIV-1 reservoir targeting and clearance methods with the ultimate goal – to cure HIV-1 infection.

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2019. p. 65
Series
TRITA-CBH-FOU ; 2019:8
Keywords
HIV-1, Latent HIV-1 reservoir, HIV-1 characterization, Microfludics, Molecular detection
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Research subject
Medical Technology
Identifiers
urn:nbn:se:kth:diva-242235 (URN)978-91-7873-089-6 (ISBN)
Public defence
2019-03-01, Air&Fire, Science for life lab, Tomtebodavägen 23a, 171 65 Solna, Stockholm, 13:00 (English)
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Note

QC 20190129

Available from: 2019-01-29 Created: 2019-01-28 Last updated: 2019-01-29Bibliographically approved

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