Discovery of candidate HIV-1 latency biomarkers using an OMICs approach

Belshan, Michael; Holbrook, Alexander K.; George, Jaiben; Durant, Hannah E.; Callahan, Michael A.; Jaquet, Spencer; West, John T.; Siedlik, Jacob A.; Ciborowski, Paweł

doi:10.1016/j.virol.2021.03.003

Cited by 4 publications

(7 citation statements)

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“…In patients infected with HIV-1, CD70 expression is upregulated in NK cells [46]. A similar phenomenon was reported in a previous study, in which the cell surface expression of both CD147 and CD231 was lower in HIV-1 latent cells [11]. Based on the important functions of CD molecules, we hypothesized that HIV-1 decreases macrophage activity by inhibiting CD protein expression to favor HIV latency.…”

Section: Discussionsupporting

confidence: 79%

“…Although ART drastically increases the survival of individuals infected with HIV [21], patients need to take drugs during their lifetime because the virus cannot be fully eradicated from its reservoirs [22]. The mechanism of HIV latency has not been completely elucidated [23], and HIV-1 latency biomarkers must be identi ed [11]. The cells of HIV-latent reservoirs are unexpectedly dynamic and diverse [24],…”

Section: Discussionmentioning

confidence: 99%

“…It is important to nd new biomarkers and mechanisms related to HIV-1 latency [23,30]. Proteomic technologies are high-throughput methods that have been widely used for studying HIV latency infection [10,11], and some potential biomarkers of HIV-1 latency have been discovered, such as LAG-3 and CypB [11], CAPG [10], burton tyrosine kinase (BTK) [12], and CD2 [31]. However, the HIV latency is much more complex and far from explicit.…”

Section: Discussionmentioning

confidence: 99%

“…OMICS technologies, such as genomics [9] and proteomics [10,11], have been used to identify potential biomarkers of HIV latency. Some proteins related to HIV latency have been discovered, such as the X-linked inhibitor of apoptosis, and phosphate of Bruton's tyrosine kinase [12], and CD30 [13].…”

Section: Introductionmentioning

confidence: 99%

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iTRAQ-based proteomic study discovered LAMP2 related to HIV-1 latency

Wang

Liu

et al. 2023

Preprint

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To identify potential biomarkers related to HIV latency on the cell surface, a subcellular proteomic study was performed using an HIV-1 latency cell line (U1 (HIV-1-integrated U937 cell line)) and a control (U937). Differentially expressed proteins were analyzed using bioinformatics, followed by western blotting and multiple reaction monitoring of cell lines and/or resting CD4 + T cells from patients. The relationship between a differentially expressed protein (lysosome-associated membrane glycoprotein 2) and HIV-1 reactivation (by panobinostat) or a lysosomotropic agent (hydroxychloroquine) was studied. Totally, 110 differentially expressed proteins were identified in U1 cells compared with U937 cells. Bioinformatics analysis suggested that the immune response and phagosomes were associated with the altered proteins. LAMP2, leukocyte surface antigen CD47, CD55 and ITGA6 were downregulated in HIV-1 latent cells. LAMP2 was downregulated in enriched resting CD4 + T cells from patients infected with HIV. LAMP2 can be upregulated after HIV-1 reactivation and hydroxychloroquine stimulation. Our results indicated that the endosomal/lysosomal pathway was involved in HIV latency in macrophage cell lines. LAMP2 down-modulation was associated with HIV latency, and the re-expression of LAMP2 accompanied the viral latency/productive infection transition. This study offers new clues for understanding the mechanism of HIV-1 latency and the eradication of HIV reservoirs.

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Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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iTRAQ-based proteomic study discovered LAMP2 related to HIV-1 latency

Wang

Liu

et al. 2023

Preprint

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“…New DIA approaches, such as sequential window acquisition of all theoretical mass spectra (SWATH-MS) combine the benefits of both targeted and shotgun approaches to provide high-throughput, accurate quantification and reproducible measurements within a single experimental setup ( 59 , 63 – 65 ). SWATH-MS has become a useful methodology in the context of drug or vaccines development ( 66 ), identification of biomarkers of HIV-1 ( 67 ), evaluation of changes in tissue-specific protein profiles in sepsis ( 68 ), evaluation of changes in the proteome under antibiotic pressure ( 69 ) and providing novel insights from central nervous system (CNS) functioning and the host response with meningitis ( 70 ).…”

Section: Modern Proteomics In the Microbiology Sequencing Eramentioning

confidence: 99%

Proteomic Approaches to Unravel Mechanisms of Antibiotic Resistance and Immune Evasion of Bacterial Pathogens

et al. 2022

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The profound effects of and distress caused by the global COVID-19 pandemic highlighted what has been known in the health sciences a long time ago: that bacteria, fungi, viruses, and parasites continue to present a major threat to human health. Infectious diseases remain the leading cause of death worldwide, with antibiotic resistance increasing exponentially due to a lack of new treatments. In addition to this, many pathogens share the common trait of having the ability to modulate, and escape from, the host immune response. The challenge in medical microbiology is to develop and apply new experimental approaches that allow for the identification of both the microbe and its drug susceptibility profile in a time-sensitive manner, as well as to elucidate their molecular mechanisms of survival and immunomodulation. Over the last three decades, proteomics has contributed to a better understanding of the underlying molecular mechanisms responsible for microbial drug resistance and pathogenicity. Proteomics has gained new momentum as a result of recent advances in mass spectrometry. Indeed, mass spectrometry-based biomedical research has been made possible thanks to technological advances in instrumentation capability and the continuous improvement of sample processing and workflows. For example, high-throughput applications such as SWATH or Trapped ion mobility enable the identification of thousands of proteins in a matter of minutes. This type of rapid, in-depth analysis, combined with other advanced, supportive applications such as data processing and artificial intelligence, presents a unique opportunity to translate knowledge-based findings into measurable impacts like new antimicrobial biomarkers and drug targets. In relation to the Research Topic “Proteomic Approaches to Unravel Mechanisms of Resistance and Immune Evasion of Bacterial Pathogens,” this review specifically seeks to highlight the synergies between the powerful fields of modern proteomics and microbiology, as well as bridging translational opportunities from biomedical research to clinical practice.

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iTRAQ-based proteomic study on monocyte cell model discovered an association of LAMP2 downregulation with HIV-1 latency

Yin,

Wang,

Liu

et al. 2024

Proteome Sci

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Background Patients with immunodeficiency virus-1 (HIV-1) infection are challenging to be cured completely due to the existence of HIV-1 latency reservoirs. However, the knowledge of the mechanisms and biomarkers associated with HIV-1 latency is limited. Therefore, identifying proteins related to HIV-1 latency could provide new insights into the underlying mechanisms of HIV-1 latency, and ultimately contribute to the eradication of HIV reservoirs. Methods An Isobaric Tags for Relative and Absolute Quantification (iTRAQ)-labeled subcellular proteomic study was performed on an HIV-1 latently infected cell model (U1, a HIV-1-integrated U937 cell line) and its control (U937). Differentially expressed proteins (DEPs) were analyzed using STRING-DB. Selected DEPs were further evaluated by western blotting and multiple reaction monitoring technology in both cell model and patient-derived cluster of differentiation 4 (CD4)+ T cells. Finally, we investigated the relationship between a specific DEP lysosome-associated membrane glycoprotein 2 (LAMP2) and HIV-1 reactivation by panobinostat or lysosome regulation by a lysosomotropic agent hydroxychloroquine in U1 and U937 cells. Results In total, 110 DEPs were identified in U1 cells comparing to U937 control cells. Bioinformatics analysis suggested associations of the altered proteins with the immune response and endosomal/lysosomal pathway. LAMP2, leukocyte surface antigen CD47, CD55, and ITGA6 were downregulated in HIV-1 latent cells. Downregulated LAMP2 was further confirmed in resting CD4+ T cells from patients with latent HIV-1 infection. Furthermore, both HIV-1 reactivation by panobinostat and stimulation with hydroxychloroquine upregulated LAMP2 expression. Conclusions Our results indicated the involvement of the endosomal/lysosomal pathway in HIV-1 latency in macrophage cell model. The down-modulation of LAMP2 was associated with HIV latency, and the restoration of LAMP2 expression accompanied the transition of viral latency to active infection. This study provides new insights into the mechanism of HIV-1 latency and potential strategies for eradicating HIV-1 reservoirs by targeting LAMP2 expression.

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Discovery of candidate HIV-1 latency biomarkers using an OMICs approach

Cited by 4 publications

References 73 publications

iTRAQ-based proteomic study discovered LAMP2 related to HIV-1 latency

iTRAQ-based proteomic study discovered LAMP2 related to HIV-1 latency

Proteomic Approaches to Unravel Mechanisms of Antibiotic Resistance and Immune Evasion of Bacterial Pathogens

iTRAQ-based proteomic study on monocyte cell model discovered an association of LAMP2 downregulation with HIV-1 latency

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