Limits...
Host Responses and Regulation by NFκB Signaling in the Liver and Liver Epithelial Cells Infected with A Novel Tick-borne Bunyavirus.

Sun Q, Jin C, Zhu L, Liang M, Li C, Cardona CJ, Li D, Xing Z - Sci Rep (2015)

Bottom Line: Viral nonstructural protein NSs was inhibitory to the induction of IFN-β, but interestingly, NFκB activation was enhanced in the presence of NSs.Therefore, NSs plays dual roles in the suppression of antiviral IFN-β induction as well as the promotion of proinflammatory responses.Our findings provide the first evidence for elucidating host responses and regulation in liver epithelial cells infected by an emerging bunyavirus.

View Article: PubMed Central - PubMed

Affiliation: The State Key Laboratory of Pharmaceutical Biotechnology and Medical School, Nanjing University, Nanjing, China.

ABSTRACT
Infection in humans by severe fever with thrombocytopenia syndrome virus (SFTSV), a novel bunyavirus transmitted by ticks, is often associated with pronounced liver damage, especially in fatal cases. Little has been known, however, about how liver cells respond to SFTSV and how the response is regulated. In this study we report that proinflammatory cytokines were induced in liver tissues of C57/BL6 mice infected with SFTSV, which may cause tissue necrosis in mice. Human liver epithelial cells were susceptible to SFTSV and antiviral interferon (IFN) and IFN-inducible proteins were induced upon infection. We observed that infection of liver epithelial cells led to significant increases in proinflammatory cytokines and chemokines, including IL-6, RANTES, IP-10, and MIP-3a, which were regulated by NFκB signaling, and the activation of NFκB signaling during infection promoted viral replication in liver epithelial cells. Viral nonstructural protein NSs was inhibitory to the induction of IFN-β, but interestingly, NFκB activation was enhanced in the presence of NSs. Therefore, NSs plays dual roles in the suppression of antiviral IFN-β induction as well as the promotion of proinflammatory responses. Our findings provide the first evidence for elucidating host responses and regulation in liver epithelial cells infected by an emerging bunyavirus.

No MeSH data available.


Related in: MedlinePlus

Apoptosis induced by infection of SFTSV in HepG2 cells.(A) Cells were infected with SFTSV at an m.o.i of 1. In situ apoptosis was detected from 24–72 hrs p.i. by an FITC-dUTP labeled TUNEL assay. (B) Transcript levels of TNF-α, FasL, and TRAIL from 6–72 hrs p.i. in infected cells were measured by realtime RT-PCR with specific primers to corresponding cytokines. (C) Concentration of TNF-α induced in infected cells. Cultural media of cells infected with SFTSV were collected at various times points p.i. and used for ELISA measurement of the concentration of TNF-α. The assays were repeated at least three times.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4488873&req=5

f3: Apoptosis induced by infection of SFTSV in HepG2 cells.(A) Cells were infected with SFTSV at an m.o.i of 1. In situ apoptosis was detected from 24–72 hrs p.i. by an FITC-dUTP labeled TUNEL assay. (B) Transcript levels of TNF-α, FasL, and TRAIL from 6–72 hrs p.i. in infected cells were measured by realtime RT-PCR with specific primers to corresponding cytokines. (C) Concentration of TNF-α induced in infected cells. Cultural media of cells infected with SFTSV were collected at various times points p.i. and used for ELISA measurement of the concentration of TNF-α. The assays were repeated at least three times.

Mentions: We next tried to characterize cell death of liver cells, which may play a role in viral pathogenesis in SFTSV infection, by examining the regulation of death receptor ligands in infected cells by realtime RT-PCR. We found that in HepG2 cells TNF-α and FasL were induced robustly up to 36- and 21-fold at 72 hr p.i. in response to infection (Fig. 3B), but TRAIL remained mainly unchanged (Fig. 3C). While mRNA transcript of TNF-α was upregulated up to 16- and 38-fold at 36 and 72 hr p.i., respectively, TNF-α concentration rose up to 1157 pg/ml in the cultural medium (Fig. 3D).


Host Responses and Regulation by NFκB Signaling in the Liver and Liver Epithelial Cells Infected with A Novel Tick-borne Bunyavirus.

Sun Q, Jin C, Zhu L, Liang M, Li C, Cardona CJ, Li D, Xing Z - Sci Rep (2015)

Apoptosis induced by infection of SFTSV in HepG2 cells.(A) Cells were infected with SFTSV at an m.o.i of 1. In situ apoptosis was detected from 24–72 hrs p.i. by an FITC-dUTP labeled TUNEL assay. (B) Transcript levels of TNF-α, FasL, and TRAIL from 6–72 hrs p.i. in infected cells were measured by realtime RT-PCR with specific primers to corresponding cytokines. (C) Concentration of TNF-α induced in infected cells. Cultural media of cells infected with SFTSV were collected at various times points p.i. and used for ELISA measurement of the concentration of TNF-α. The assays were repeated at least three times.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4488873&req=5

f3: Apoptosis induced by infection of SFTSV in HepG2 cells.(A) Cells were infected with SFTSV at an m.o.i of 1. In situ apoptosis was detected from 24–72 hrs p.i. by an FITC-dUTP labeled TUNEL assay. (B) Transcript levels of TNF-α, FasL, and TRAIL from 6–72 hrs p.i. in infected cells were measured by realtime RT-PCR with specific primers to corresponding cytokines. (C) Concentration of TNF-α induced in infected cells. Cultural media of cells infected with SFTSV were collected at various times points p.i. and used for ELISA measurement of the concentration of TNF-α. The assays were repeated at least three times.
Mentions: We next tried to characterize cell death of liver cells, which may play a role in viral pathogenesis in SFTSV infection, by examining the regulation of death receptor ligands in infected cells by realtime RT-PCR. We found that in HepG2 cells TNF-α and FasL were induced robustly up to 36- and 21-fold at 72 hr p.i. in response to infection (Fig. 3B), but TRAIL remained mainly unchanged (Fig. 3C). While mRNA transcript of TNF-α was upregulated up to 16- and 38-fold at 36 and 72 hr p.i., respectively, TNF-α concentration rose up to 1157 pg/ml in the cultural medium (Fig. 3D).

Bottom Line: Viral nonstructural protein NSs was inhibitory to the induction of IFN-β, but interestingly, NFκB activation was enhanced in the presence of NSs.Therefore, NSs plays dual roles in the suppression of antiviral IFN-β induction as well as the promotion of proinflammatory responses.Our findings provide the first evidence for elucidating host responses and regulation in liver epithelial cells infected by an emerging bunyavirus.

View Article: PubMed Central - PubMed

Affiliation: The State Key Laboratory of Pharmaceutical Biotechnology and Medical School, Nanjing University, Nanjing, China.

ABSTRACT
Infection in humans by severe fever with thrombocytopenia syndrome virus (SFTSV), a novel bunyavirus transmitted by ticks, is often associated with pronounced liver damage, especially in fatal cases. Little has been known, however, about how liver cells respond to SFTSV and how the response is regulated. In this study we report that proinflammatory cytokines were induced in liver tissues of C57/BL6 mice infected with SFTSV, which may cause tissue necrosis in mice. Human liver epithelial cells were susceptible to SFTSV and antiviral interferon (IFN) and IFN-inducible proteins were induced upon infection. We observed that infection of liver epithelial cells led to significant increases in proinflammatory cytokines and chemokines, including IL-6, RANTES, IP-10, and MIP-3a, which were regulated by NFκB signaling, and the activation of NFκB signaling during infection promoted viral replication in liver epithelial cells. Viral nonstructural protein NSs was inhibitory to the induction of IFN-β, but interestingly, NFκB activation was enhanced in the presence of NSs. Therefore, NSs plays dual roles in the suppression of antiviral IFN-β induction as well as the promotion of proinflammatory responses. Our findings provide the first evidence for elucidating host responses and regulation in liver epithelial cells infected by an emerging bunyavirus.

No MeSH data available.


Related in: MedlinePlus