Functional proteomic atlas of HIV infection in primary human CD4+ T cells

Naamati, Adi; Williamson, James C; Greenwood, Edward Jd; Marelli, Sara; Lehner, Paul J.; Matheson, Nicholas J

doi:10.7554/elife.41431

Cited by 39 publications

(58 citation statements)

References 105 publications

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“…C -Classical monocyte sample, I -Intermediate monocyte sample, NC -Non-classical monocyte sample. (2020) 10:4560 | https://doi.org/10.1038/s41598-020-61356-w www.nature.com/scientificreports www.nature.com/scientificreports/ other cell surface proteomic analyses in primary cells have been limited to CD4+ T-cells 16 , erythrocytes 17,18 , NK cells, adipocytes and a subset of tumour cells 19 . We quantify 373 cell surface proteins from classical monocytes, and further quantify 313 proteins across all monocyte subsets.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive cell surface proteomics defines markers of classical, intermediate and non-classical monocytes

Ravenhill

Soday

Houghton

et al. 2020

Sci Rep

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Monocytes are a critical component of the cellular innate immune system, and can be subdivided into classical, intermediate and non-classical subsets on the basis of surface CD14 and CD16 expression. classical monocytes play the canonical role of phagocytosis, and account for the majority of circulating cells. Intermediate and non-classical cells are known to exhibit varying levels of phagocytosis and cytokine secretion, and are differentially expanded in certain pathological states. Characterisation of cell surface proteins expressed by each subset is informative not only to improve understanding of phenotype, but may also provide biological insights into function. Here we use highly multiplexed Tandem-Mass-Tag (TMT)-based mass spectrometry with selective cell surface biotinylation to characterise the classical monocyte surface proteome, then interrogate the phenotypic differences between each monocyte subset to identify novel protein markers. Monocytes play critical roles in the response to infection and inflammation and antigen presentation. Key effector functions are mediated by differentiated cells, including macrophages and myeloid dendritic cells. Monocytes can be divided into subsets based on the presence of the cell surface lipopolysaccharide (LPS) co-receptor CD14, and Fc-Gamma Receptor III (CD16). CD14++ CD16− classical monocytes account for ~85% of circulating monocytes, intermediate cells (CD14++ CD16+) for ~5% and non-classical cells (CD14+ CD16++) for ~10% of circulating monocytes 1,2. It has become increasingly well established that each subset plays divergent roles in different diseases, as well as differing in the ability to secrete cytokines and respond to pathogen associated molecular patterns (PAMPs). Classical monocytes are phagocytic and readily secrete inflammatory cytokines. Conversely, the CD16 positive non-classical cells are poorly phagocytic and are suggested to secrete TNFα in response to some stimuli, but less of other pro-inflammatory molecules 2-4. Intermediate monocytes are increased in diseases such as severe asthma, rheumatoid arthritis and sarcoidosis, and there is some evidence for expansion of classical monocytes in atherosclerosis 5-8. It is still unclear whether intermediate monocytes represent a truly distinct monocyte subset, or merely a transitional stage between classical and non-classical cells 9. Cells of the innate and adaptive immune systems can be categorised on the basis of microscopic appearance and expression of plasma membrane (PM) proteins, enabling separation by fluorescence activated cell sorting (FACS). As such, systematic evaluation of the entire cell surface proteome expressed by a given immune cell population is a powerful tool to characterise cellular function and distinguish cell types. Previous studies of monocytes subsets have examined transcriptional differences and offer varying depths of information about subset markers, suitability of individual proteins for discriminating subsets by cell surface flow cytometry and the importance of each protein...

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Section: Discussionmentioning

confidence: 99%

Comprehensive cell surface proteomics defines markers of classical, intermediate and non-classical monocytes

Ravenhill

Soday

Houghton

et al. 2020

Sci Rep

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“…This represents the first cell surface proteomic study in primary monocyte subsets. Up to now, other cell surface proteomic analyses in primary cells have been limited to CD4+ T-cells 16 , erythrocytes 17,18 , NK cells, adipocytes and a subset of tumour cells 19 . We quantify 373 cell surface proteins from classical monocytes, and further quantify 313 proteins across all monocyte subsets.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive cell surface proteomics defines markers of classical, intermediate and non-classical monocytes

Ravenhill

Soday

Houghton

et al. 2020

Preprint

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“…Vpr/Vif-mediated G2/M arrest studies have been performed in cycling cells including T cell lines [107,109,111,113,121,122], THP-1 [99], Hela and HEK293 [98,113,122], and primary CD4 T cells [120,123].…”

Section: What Is the Role Of Vpr/vif-mediated G2/m Arrest In Terminalmentioning

confidence: 99%

“…Indeed the Vif-dependent depletion of PPP2R5A causes an increase in protein phosphorylation in HIV-infected cells, including that of substrates of the aurora kinases and CDK1 [ 114 ]. It has been concluded that the depletion of the PPP2R5 family subunits is necessary for Vif-dependent cell cycle arrest [ 101 , 113 , 119 , 120 ].…”

Section: Hiv-1 Regulates the Host Cell Cyclementioning

confidence: 99%

Cell Cycle Regulation in Macrophages and Susceptibility to HIV-1

Ferreira

Porterfield

Gupta

et al. 2020

Viruses

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Macrophages are the first line of defence against invading pathogens. They play a crucial role in immunity but also in regeneration and homeostasis. Their remarkable plasticity in their phenotypes and function provides them with the ability to quickly respond to environmental changes and infection. Recent work shows that macrophages undergo cell cycle transition from a G0/terminally differentiated state to a G1 state. This G0-to-G1 transition presents a window of opportunity for HIV-1 infection. Macrophages are an important target for HIV-1 but express high levels of the deoxynucleotide-triphosphate hydrolase SAMHD1, which restricts viral DNA synthesis by decreasing levels of dNTPs. While the G0 state is non-permissive to HIV-1 infection, a G1 state is very permissive to HIV-1 infection. This is because macrophages in a G1 state switch off the antiviral restriction factor SAMHD1 by phosphorylation, thereby allowing productive HIV-1 infection. Here, we explore the macrophage cell cycle and the interplay between its regulation and permissivity to HIV-1 infection.

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Functional proteomic atlas of HIV infection in primary human CD4+ T cells

Cited by 39 publications

References 105 publications

Comprehensive cell surface proteomics defines markers of classical, intermediate and non-classical monocytes

Comprehensive cell surface proteomics defines markers of classical, intermediate and non-classical monocytes

Comprehensive cell surface proteomics defines markers of classical, intermediate and non-classical monocytes

Cell Cycle Regulation in Macrophages and Susceptibility to HIV-1

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