Proteomics, biomarkers, and HIV‐1: A current perspective

Donnelly, Maire Rose; Ciborowski, Paweł

doi:10.1002/prca.201500002

Cited by 17 publications

(19 citation statements)

References 99 publications

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“…However, lack of detection of Tat in exosomes from the infected cells in these two studies cannot simply be interpreted as absence of the protein. LC-MS/MS has not been detected Tat protein in HIV-producing CD4 T cells (Li 2015; Santos et al 2012; Saphire et al 2006) and in sera of HIV-infected patients (Donnelly and Ciborowski 2016). Only one study has detected Tat protein in purified HIV using LC-MS/MS in combination with micro-capillary reversed-phase liquid chromatography (µRPLC) (Chertova et al 2006), which has been shown to improve detection of low-abundant proteins such as Tat (Tomlinson and Chicz 2003).…”

Section: Discussionmentioning

confidence: 99%

Exosome-associated release, uptake, and neurotoxicity of HIV-1 Tat protein

Rahimian

2016

J. Neurovirol.

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HIV-1 Tat is an indispensible transactivator for HIV gene transcription and replication. It has been shown to exit cells as a free protein and enter neighboring cells or interact with surface receptors of neighboring cells to regulate gene expression and cell function. In this study, we report, for the first time, exosome-associated Tat release and uptake. Using a HIV-1 LTR-driven luciferase reporter-based cell assay and Western blotting or in combination with exosome inhibitor, OptiPrep gradient fractionation, and exosome depletion, we demonstrated significant presence of HIV-1 Tat in exosomes derived from Tat-expressing primary astrocytes, Tat-transfected U373.MG and 293T, and HIV-infected MT4. We further showed that exosome-associated Tat from Tat-expressing astrocytes was capable of causing neurite shortening and neuron death, further supporting that this new form of extracellular Tat is biologically active. Lastly, we constructed a Tat mutant deleted of its basic domain and determined the role of the basic domain in Tat trafficking into exosomes. Basic domain-deleted Tat exhibited no apparent effects on Tat trafficking into exosomes, while maintained its dominant-negative function in Tat-mediated LTR transactivation. Taken together, these results show a significant fraction of Tat is secreted and present in the form of exosomes and may contribute to the stability of extracellular Tat and broaden the spectrum of its target cells.

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Section: Discussionmentioning

confidence: 99%

Exosome-associated release, uptake, and neurotoxicity of HIV-1 Tat protein

Rahimian

2016

J. Neurovirol.

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“…Every step brings with it some degree of variability. [ 14 ] Sample preparation, instrumentation, targeted versus global approaches, and data analysis are a few of the factors that influence results, and thus the conclusions are drawn and knowledge gained. These issues can make it difficult to compare study results and to build a clearer picture of HIV infection in macrophages, and ultimately, of HIV infection in humans overall.…”

Section: Quantitative Proteomics: Experimental Design To Maximize Thementioning

confidence: 99%

“…For a more comprehensive discussion of viral proteins, we refer readers to our previous review. [ 14 ]…”

Section: Viral Proteinsmentioning

confidence: 99%

HIV and Proteomics: What We Have Learned from High Throughput Studies

Grabowska

Harwood

Ciborowski

2020

Proteomics Clinical Apps

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The accelerated development of technology over the last three decades has driven biological sciences to high-throughput profiling experiments, now broadly referred to as systems biology. The unprecedented improvement of analytical instrumentation has opened new avenues for more complex experimental designs and expands the knowledge in genomics, proteomics, and other omics fields. Despite the collective efforts of hundreds of researchers, gleaning all the expected information from omics experiments is still quite far. This paper summarizes what has been learned from high-throughput proteomics studies thus far, and what is believed should be done to reveal even more valuable information from such studies. It is drawn from the background in using proteomics to study human immunodeficiency virus 1 infection of macrophages and/or T cells, but it is believed that some conclusions will be more broadly applicable.

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“…Some proteomic studies have also been performed, but they were not very reproducible, as indicated in a recent review by Donnelly and Ciborowski (2016). To our knowledge, few epigenomic studies have been published to date in HIV/AIDS.…”

Section: Proteomic and Epigenomic Studiesmentioning

confidence: 99%

Large-Scale “OMICS” Studies to Explore the Physiopatholgy of HIV-1 Infection

2019

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In this review, we present the main large-scale experimental studies that have been performed in the HIV/AIDS field. These “omics” studies are based on several technologies including genotyping, RNA interference, and transcriptome or epigenome analysis. Due to the direct connection with disease evolution, there has been a large focus on genotyping cohorts of well-characterized patients through genome-wide association studies (GWASs), but there have also been several invitro studies such as small interfering RNA (siRNA) interference or transcriptome analyses of HIV-1–infected cells. After describing the major results obtained with these omics technologies—including some with a high relevance for HIV-1 treatment—we discuss the next steps that the community needs to embrace in order to derive new actionable therapeutic or diagnostic targets. Only integrative approaches that combine all big data results and consider their complex interactions will allow us to capture the global picture of HIV molecular pathogenesis. This novel challenge will require large collaborative efforts and represents a huge open field for innovative bioinformatics approaches.

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Proteomics, biomarkers, and HIV‐1: A current perspective

Cited by 17 publications

References 99 publications

Exosome-associated release, uptake, and neurotoxicity of HIV-1 Tat protein

Exosome-associated release, uptake, and neurotoxicity of HIV-1 Tat protein

HIV and Proteomics: What We Have Learned from High Throughput Studies

Large-Scale “OMICS” Studies to Explore the Physiopatholgy of HIV-1 Infection

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