2019
DOI: 10.1371/journal.ppat.1008062
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Induction of PGRN by influenza virus inhibits the antiviral immune responses through downregulation of type I interferons signaling

Abstract: Type I interferons (IFNs) play a critical role in host defense against influenza virus infection, and the mechanism of influenza virus to evade type I IFNs responses remains to be fully understood. Here, we found that progranulin (PGRN) was significantly increased both in vitro and in vivo during influenza virus infection. Using a PGRN knockdown assay and PGRN-deficient mice model, we demonstrated that influenza virus-inducing PGRN negatively regulated type I IFNs production by inhibiting the activation of NF-… Show more

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Cited by 29 publications
(27 citation statements)
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“…Third, ORM1 , which drives the differentiation of monocytes to anti-inflammatory M2b macrophages (Nakamura et al, 2015), was significantly different between the two trajectories. Fourth, genes known to reduce the type I interferon response, GRN and BCL6 (Wei et al, 2019; Wu et al, 2016), were positively correlated with severity ( Figure S4C ). Most importantly, all genes but GRN positively correlated with severity in the independent cohort of patients with SARS-CoV-2 infection ( Figure 5H and Figure S4D ).…”
Section: Resultsmentioning
confidence: 98%
“…Third, ORM1 , which drives the differentiation of monocytes to anti-inflammatory M2b macrophages (Nakamura et al, 2015), was significantly different between the two trajectories. Fourth, genes known to reduce the type I interferon response, GRN and BCL6 (Wei et al, 2019; Wu et al, 2016), were positively correlated with severity ( Figure S4C ). Most importantly, all genes but GRN positively correlated with severity in the independent cohort of patients with SARS-CoV-2 infection ( Figure 5H and Figure S4D ).…”
Section: Resultsmentioning
confidence: 98%
“…The hPIV V protein interacts with MDA5 to inhibit STAT activation and downstream signaling, and hPIV's C and V proteins directly inhibit STAT1 phosphorylation in the IFNλ signaling cascade (48,49). NF-κB and various interferon regulatory factors (IRFs), often IRF/3/7, are inhibited or degraded by IAV progranulin (PGRN) and type 2 cytokines produced by RV infection (50,51). The RSV F protein also inhibits IRF1 outside of the classical IFNλ signaling pathway through activation of the epithelial growth factor receptor (EGFR) (52).…”
Section: Type I and Iii Interferon Responses In The Lungmentioning
confidence: 99%
“…ORM1 , which drives the differentiation of monocytes to anti-inflammatory M2b macrophages ( Nakamura et al., 2015 ), was significantly different between the two trajectories. Genes known to reduce the type I interferon (IFN) response, GRN and BCL6 ( Wei et al., 2019 ; Wu et al., 2016 ), were positively correlated with severity ( Figure S4 C). All genes but GRN positively correlated with severity in the independent cohort of patients with SARS-CoV-2 infection ( Figure 5 H, Figure S4 D).…”
Section: Resultsmentioning
confidence: 99%