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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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Modulation of Viral Restriction Factors during HCMV Infection, Related to Figure 2(A) Sp100 is known to be targeted for degradation by HCMV IE1 (Kim et al., 2011a). Modulation of SAMHD1, ZAP and SLFN11 had not previously been recognized.(B) Quantitation of 21 TRIMs during infection. Results are shown from experiments WCL2 (top sets of panels) and WCL1 (bottom sets of panels). 8 TRIMs were not quantified in experiment WCL1. One-way ANOVA with multiple hypothesis correction (experiment WCL1): ∗p < 0.005.Red diamonds – 12h after infection with irradiated HCMV.
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figs2: Modulation of Viral Restriction Factors during HCMV Infection, Related to Figure 2(A) Sp100 is known to be targeted for degradation by HCMV IE1 (Kim et al., 2011a). Modulation of SAMHD1, ZAP and SLFN11 had not previously been recognized.(B) Quantitation of 21 TRIMs during infection. Results are shown from experiments WCL2 (top sets of panels) and WCL1 (bottom sets of panels). 8 TRIMs were not quantified in experiment WCL1. One-way ANOVA with multiple hypothesis correction (experiment WCL1): ∗p < 0.005.Red diamonds – 12h after infection with irradiated HCMV.

Mentions: We therefore performed a comprehensive search of all other known interferon-induced antiviral genes, to determine which might be similarly or otherwise modulated during HCMV infection (Duggal and Emerman, 2012; Schoggins et al., 2011). Our results were consistent with the reported degradation of RIG-I and of the nuclear HCMV restriction factor Sp100 during infection (Figures 2A and S2A, respectively) (Kim et al., 2011a; Scott, 2009). Many of the tripartite motif-containing proteins (TRIMs) are interferon induced. TRIM5α can restrict HIV, although no viral factor is yet known to antagonize its expression (Rahm and Telenti, 2012). We quantified 21 TRIMs, of which TRIM 5, 16, 22, and 38 were downregulated during infection (Figure S2B). SAM Domain and HD Domain 1 (SAMHD1), zinc finger CCCH-type, antiviral 1 (ZAP/ZC3HAV1), and the novel anti-HIV factor Schlafen 11 (SLFN11) behaved similarly to members of cluster A (Figure S2A). It remains to be determined whether any of these antiviral proteins can restrict HCMV, and if reduction in their expression simply reflects diminished IFN signaling and response, or selective targeting by virus.


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)

Modulation of Viral Restriction Factors during HCMV Infection, Related to Figure 2(A) Sp100 is known to be targeted for degradation by HCMV IE1 (Kim et al., 2011a). Modulation of SAMHD1, ZAP and SLFN11 had not previously been recognized.(B) Quantitation of 21 TRIMs during infection. Results are shown from experiments WCL2 (top sets of panels) and WCL1 (bottom sets of panels). 8 TRIMs were not quantified in experiment WCL1. One-way ANOVA with multiple hypothesis correction (experiment WCL1): ∗p < 0.005.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

figs2: Modulation of Viral Restriction Factors during HCMV Infection, Related to Figure 2(A) Sp100 is known to be targeted for degradation by HCMV IE1 (Kim et al., 2011a). Modulation of SAMHD1, ZAP and SLFN11 had not previously been recognized.(B) Quantitation of 21 TRIMs during infection. Results are shown from experiments WCL2 (top sets of panels) and WCL1 (bottom sets of panels). 8 TRIMs were not quantified in experiment WCL1. One-way ANOVA with multiple hypothesis correction (experiment WCL1): ∗p < 0.005.Red diamonds – 12h after infection with irradiated HCMV.
Mentions: We therefore performed a comprehensive search of all other known interferon-induced antiviral genes, to determine which might be similarly or otherwise modulated during HCMV infection (Duggal and Emerman, 2012; Schoggins et al., 2011). Our results were consistent with the reported degradation of RIG-I and of the nuclear HCMV restriction factor Sp100 during infection (Figures 2A and S2A, respectively) (Kim et al., 2011a; Scott, 2009). Many of the tripartite motif-containing proteins (TRIMs) are interferon induced. TRIM5α can restrict HIV, although no viral factor is yet known to antagonize its expression (Rahm and Telenti, 2012). We quantified 21 TRIMs, of which TRIM 5, 16, 22, and 38 were downregulated during infection (Figure S2B). SAM Domain and HD Domain 1 (SAMHD1), zinc finger CCCH-type, antiviral 1 (ZAP/ZC3HAV1), and the novel anti-HIV factor Schlafen 11 (SLFN11) behaved similarly to members of cluster A (Figure S2A). It remains to be determined whether any of these antiviral proteins can restrict HCMV, and if reduction in their expression simply reflects diminished IFN signaling and response, or selective targeting by virus.

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