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Global Reprogramming of Host SUMOylation during Influenza Virus Infection.

Domingues P, Golebiowski F, Tatham MH, Lopes AM, Taggart A, Hay RT, Hale BG - Cell Rep (2015)

Bottom Line: This is paralleled by widespread host deSUMOylation.Depletion screening identified ten virus-induced SUMO targets as potential antiviral factors, including C18orf25 and the SMC5/6 and PAF1 complexes.Mechanistic studies further uncovered a role for SUMOylation of the PAF1 complex component, parafibromin (CDC73), in potentiating antiviral gene expression.

View Article: PubMed Central - PubMed

Affiliation: MRC-University of Glasgow Centre for Virus Research, Garscube Campus, 464 Bearsden Road, Glasgow G61 1QH, UK.

No MeSH data available.


Related in: MedlinePlus

SUMO Conjugation Patterns and Intracellular Distribution following Infection with a Panel of Nuclear- and Cytoplasmic-Replicating RNA Viruses(A) Western blot of lysates from A549s infected with IAV (5 PFU/cell) as indicated. SUMO1, SUMO2/3, NS1, and actin were detected.(B and C) Western blot of Vero cells infected with IAV or influenza B virus (IBV) for 16 hr at 33°C (B) or infected with IAV, LACV, VSV, or SFV for 12 hr at 37°C (all ∼5 PFU/cell) (C). SUMO2/3, actin, and individual viral proteins were detected.(D and E) Immunofluorescent analysis and quantification of MRC5s infected with IAV at 0.1 PFU/cell as indicated. SUMO1 and SUMO2/3 (D) or hDaxx, SP100, PML (E), and IAV NP were visualized after staining. Scale bars represent 5 μm. Statistical significance (∗∗∗p < 0.0001) in (D) was determined using the Student’s t test. See also Figure S1.
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fig1: SUMO Conjugation Patterns and Intracellular Distribution following Infection with a Panel of Nuclear- and Cytoplasmic-Replicating RNA Viruses(A) Western blot of lysates from A549s infected with IAV (5 PFU/cell) as indicated. SUMO1, SUMO2/3, NS1, and actin were detected.(B and C) Western blot of Vero cells infected with IAV or influenza B virus (IBV) for 16 hr at 33°C (B) or infected with IAV, LACV, VSV, or SFV for 12 hr at 37°C (all ∼5 PFU/cell) (C). SUMO2/3, actin, and individual viral proteins were detected.(D and E) Immunofluorescent analysis and quantification of MRC5s infected with IAV at 0.1 PFU/cell as indicated. SUMO1 and SUMO2/3 (D) or hDaxx, SP100, PML (E), and IAV NP were visualized after staining. Scale bars represent 5 μm. Statistical significance (∗∗∗p < 0.0001) in (D) was determined using the Student’s t test. See also Figure S1.

Mentions: Human cells express three main SUMO paralogues as follows: SUMO2 and SUMO3, which only differ by 3 amino acids in their mature state (hereafter referred to as SUMO2/3); and SUMO1, which shares ∼50% sequence identity with SUMO2/3. Consistent with the results of others (Pal et al., 2011), western blot analysis of total human lung epithelial cell (A549) lysates revealed that IAV infection triggers an increase in the abundance of proteins modified by both SUMO1 and SUMO2/3, whereas the amounts of free, unconjugated SUMO1 and SUMO2/3 are depleted (Figure 1A). This SUMOylation response is not due to an increase in SUMO mRNA transcripts during infection (Figure S1A), indicating that new SUMO conjugates arise from the pre-existing SUMO pool. Furthermore, this response is not unique to IAV, as influenza B virus (which also replicates in the nucleus) triggered similar SUMO conjugate induction during infection (Figure 1B). Nevertheless, infection with a panel of cytoplasmic-replicating RNA viruses (including members of the Bunyaviridae [−ve sense, segmented RNA genome], Rhabdoviridae [−ve sense, single-stranded RNA genome], and Togaviridae [+ve sense, single-stranded RNA genome]) revealed that these viruses do not trigger gross SUMO conjugate induction (Figure 1C). These data suggest a specific induction of SUMO conjugates in response to nuclear-replicating influenza viruses.


Global Reprogramming of Host SUMOylation during Influenza Virus Infection.

Domingues P, Golebiowski F, Tatham MH, Lopes AM, Taggart A, Hay RT, Hale BG - Cell Rep (2015)

SUMO Conjugation Patterns and Intracellular Distribution following Infection with a Panel of Nuclear- and Cytoplasmic-Replicating RNA Viruses(A) Western blot of lysates from A549s infected with IAV (5 PFU/cell) as indicated. SUMO1, SUMO2/3, NS1, and actin were detected.(B and C) Western blot of Vero cells infected with IAV or influenza B virus (IBV) for 16 hr at 33°C (B) or infected with IAV, LACV, VSV, or SFV for 12 hr at 37°C (all ∼5 PFU/cell) (C). SUMO2/3, actin, and individual viral proteins were detected.(D and E) Immunofluorescent analysis and quantification of MRC5s infected with IAV at 0.1 PFU/cell as indicated. SUMO1 and SUMO2/3 (D) or hDaxx, SP100, PML (E), and IAV NP were visualized after staining. Scale bars represent 5 μm. Statistical significance (∗∗∗p < 0.0001) in (D) was determined using the Student’s t test. See also Figure S1.
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fig1: SUMO Conjugation Patterns and Intracellular Distribution following Infection with a Panel of Nuclear- and Cytoplasmic-Replicating RNA Viruses(A) Western blot of lysates from A549s infected with IAV (5 PFU/cell) as indicated. SUMO1, SUMO2/3, NS1, and actin were detected.(B and C) Western blot of Vero cells infected with IAV or influenza B virus (IBV) for 16 hr at 33°C (B) or infected with IAV, LACV, VSV, or SFV for 12 hr at 37°C (all ∼5 PFU/cell) (C). SUMO2/3, actin, and individual viral proteins were detected.(D and E) Immunofluorescent analysis and quantification of MRC5s infected with IAV at 0.1 PFU/cell as indicated. SUMO1 and SUMO2/3 (D) or hDaxx, SP100, PML (E), and IAV NP were visualized after staining. Scale bars represent 5 μm. Statistical significance (∗∗∗p < 0.0001) in (D) was determined using the Student’s t test. See also Figure S1.
Mentions: Human cells express three main SUMO paralogues as follows: SUMO2 and SUMO3, which only differ by 3 amino acids in their mature state (hereafter referred to as SUMO2/3); and SUMO1, which shares ∼50% sequence identity with SUMO2/3. Consistent with the results of others (Pal et al., 2011), western blot analysis of total human lung epithelial cell (A549) lysates revealed that IAV infection triggers an increase in the abundance of proteins modified by both SUMO1 and SUMO2/3, whereas the amounts of free, unconjugated SUMO1 and SUMO2/3 are depleted (Figure 1A). This SUMOylation response is not due to an increase in SUMO mRNA transcripts during infection (Figure S1A), indicating that new SUMO conjugates arise from the pre-existing SUMO pool. Furthermore, this response is not unique to IAV, as influenza B virus (which also replicates in the nucleus) triggered similar SUMO conjugate induction during infection (Figure 1B). Nevertheless, infection with a panel of cytoplasmic-replicating RNA viruses (including members of the Bunyaviridae [−ve sense, segmented RNA genome], Rhabdoviridae [−ve sense, single-stranded RNA genome], and Togaviridae [+ve sense, single-stranded RNA genome]) revealed that these viruses do not trigger gross SUMO conjugate induction (Figure 1C). These data suggest a specific induction of SUMO conjugates in response to nuclear-replicating influenza viruses.

Bottom Line: This is paralleled by widespread host deSUMOylation.Depletion screening identified ten virus-induced SUMO targets as potential antiviral factors, including C18orf25 and the SMC5/6 and PAF1 complexes.Mechanistic studies further uncovered a role for SUMOylation of the PAF1 complex component, parafibromin (CDC73), in potentiating antiviral gene expression.

View Article: PubMed Central - PubMed

Affiliation: MRC-University of Glasgow Centre for Virus Research, Garscube Campus, 464 Bearsden Road, Glasgow G61 1QH, UK.

No MeSH data available.


Related in: MedlinePlus