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Quantitative temporal viromics: an approach to investigate host-pathogen interaction.

Weekes MP, Tomasec P, Huttlin EL, Fielding CA, Nusinow D, Stanton RJ, Wang EC, Aicheler R, Murrell I, Wilkinson GW, Lehner PJ, Gygi SP - Cell (2014)

Bottom Line: QTV predicted natural killer and T cell ligands, as well as 29 viral proteins present at the cell surface, potential therapeutic targets.Temporal profiles of >80% of HCMV canonical genes and 14 noncanonical HCMV open reading frames were defined.QTV is a powerful method that can yield important insights into viral infection and is applicable to any virus with a robust in vitro model.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA; Cambridge Institute for Medical Research, University of Cambridge, Hills Road, Cambridge CB2 0XY, UK. Electronic address: mpw1001@cam.ac.uk.

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QTV Informs about Mechanism of Modulation of Cell-Surface Targets, Related to Figure 7(A) Further examples of mechanistic insights into downregulated cell surface immunomodulators. TRAILR2 is retained in the ER by UL141 (Smith et al., 2013). MICA is retained in the cis-Golgi by UL142 (Ashiru et al., 2009). UL142 was only quantified at the plasma membrane (Figure S5A) and is not shown here.(B) Examples of mechanistic insights into upregulated cell surface ligands, or receptors with complex patterns of expression. Signal peptide from HCMV UL40 acts to promote cell surface expression of HLA-E (Prod’homme et al., 2012). The WCL pattern of expression of UL40 was extremely similar to cell surface HLA-E, and is shown overlying both PM and WCL data to illustrate this. TNFR1 cell surface expression is upregulated by UL138, which has a dominant effect. Other virally encoded functions may downregulate TNFR1 expression (Montag et al., 2011). The WCL pattern of expression of UL138 is shown overlying both PM and WCL data.Red diamonds – 12h after infection with irradiated HCMV.
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figs7: QTV Informs about Mechanism of Modulation of Cell-Surface Targets, Related to Figure 7(A) Further examples of mechanistic insights into downregulated cell surface immunomodulators. TRAILR2 is retained in the ER by UL141 (Smith et al., 2013). MICA is retained in the cis-Golgi by UL142 (Ashiru et al., 2009). UL142 was only quantified at the plasma membrane (Figure S5A) and is not shown here.(B) Examples of mechanistic insights into upregulated cell surface ligands, or receptors with complex patterns of expression. Signal peptide from HCMV UL40 acts to promote cell surface expression of HLA-E (Prod’homme et al., 2012). The WCL pattern of expression of UL40 was extremely similar to cell surface HLA-E, and is shown overlying both PM and WCL data to illustrate this. TNFR1 cell surface expression is upregulated by UL138, which has a dominant effect. Other virally encoded functions may downregulate TNFR1 expression (Montag et al., 2011). The WCL pattern of expression of UL138 is shown overlying both PM and WCL data.Red diamonds – 12h after infection with irradiated HCMV.

Mentions: We therefore examined other HCMV proteins known to target cell-surface receptors (Table S1A). The profiles of UL138 and ABCC1 were consistent with their codegradation (Weekes et al., 2013), and the profile of HLA-A reflected US2 and US11-mediated degradation (Figure 7B). Other examples are shown in Figures S7A and S7B. The temporal profiles provided by QTV are thus useful to gain mechanistic insights into known interactions between viral and host proteins.


Quantitative temporal viromics: an approach to investigate host-pathogen interaction.

Weekes MP, Tomasec P, Huttlin EL, Fielding CA, Nusinow D, Stanton RJ, Wang EC, Aicheler R, Murrell I, Wilkinson GW, Lehner PJ, Gygi SP - Cell (2014)

QTV Informs about Mechanism of Modulation of Cell-Surface Targets, Related to Figure 7(A) Further examples of mechanistic insights into downregulated cell surface immunomodulators. TRAILR2 is retained in the ER by UL141 (Smith et al., 2013). MICA is retained in the cis-Golgi by UL142 (Ashiru et al., 2009). UL142 was only quantified at the plasma membrane (Figure S5A) and is not shown here.(B) Examples of mechanistic insights into upregulated cell surface ligands, or receptors with complex patterns of expression. Signal peptide from HCMV UL40 acts to promote cell surface expression of HLA-E (Prod’homme et al., 2012). The WCL pattern of expression of UL40 was extremely similar to cell surface HLA-E, and is shown overlying both PM and WCL data to illustrate this. TNFR1 cell surface expression is upregulated by UL138, which has a dominant effect. Other virally encoded functions may downregulate TNFR1 expression (Montag et al., 2011). The WCL pattern of expression of UL138 is shown overlying both PM and WCL data.Red diamonds – 12h after infection with irradiated HCMV.
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4048463&req=5

figs7: QTV Informs about Mechanism of Modulation of Cell-Surface Targets, Related to Figure 7(A) Further examples of mechanistic insights into downregulated cell surface immunomodulators. TRAILR2 is retained in the ER by UL141 (Smith et al., 2013). MICA is retained in the cis-Golgi by UL142 (Ashiru et al., 2009). UL142 was only quantified at the plasma membrane (Figure S5A) and is not shown here.(B) Examples of mechanistic insights into upregulated cell surface ligands, or receptors with complex patterns of expression. Signal peptide from HCMV UL40 acts to promote cell surface expression of HLA-E (Prod’homme et al., 2012). The WCL pattern of expression of UL40 was extremely similar to cell surface HLA-E, and is shown overlying both PM and WCL data to illustrate this. TNFR1 cell surface expression is upregulated by UL138, which has a dominant effect. Other virally encoded functions may downregulate TNFR1 expression (Montag et al., 2011). The WCL pattern of expression of UL138 is shown overlying both PM and WCL data.Red diamonds – 12h after infection with irradiated HCMV.
Mentions: We therefore examined other HCMV proteins known to target cell-surface receptors (Table S1A). The profiles of UL138 and ABCC1 were consistent with their codegradation (Weekes et al., 2013), and the profile of HLA-A reflected US2 and US11-mediated degradation (Figure 7B). Other examples are shown in Figures S7A and S7B. The temporal profiles provided by QTV are thus useful to gain mechanistic insights into known interactions between viral and host proteins.

Bottom Line: QTV predicted natural killer and T cell ligands, as well as 29 viral proteins present at the cell surface, potential therapeutic targets.Temporal profiles of >80% of HCMV canonical genes and 14 noncanonical HCMV open reading frames were defined.QTV is a powerful method that can yield important insights into viral infection and is applicable to any virus with a robust in vitro model.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA; Cambridge Institute for Medical Research, University of Cambridge, Hills Road, Cambridge CB2 0XY, UK. Electronic address: mpw1001@cam.ac.uk.

Show MeSH
Related in: MedlinePlus