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

Induction of IFN-β was suppressed by NSs.HepG2 (A, B and C) and HeLa (D, E and F) cells were transfected with cDNA expressing HA-tagged NSs or blank plasmid. After 24 hrs, the cells were mock infected or infected with SFTSV. Total RNA was prepared from non-infected and infected cells at various time points p.i., and real-time RT-PCR was performed to measure the levels of IFN-β (A and D) and viral S gene copy numbers (C and F). Cultural media of HepG2 cells were collected at various times points p.i. for ELISA to measure the concentration of IFN-β (B and E).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f10: Induction of IFN-β was suppressed by NSs.HepG2 (A, B and C) and HeLa (D, E and F) cells were transfected with cDNA expressing HA-tagged NSs or blank plasmid. After 24 hrs, the cells were mock infected or infected with SFTSV. Total RNA was prepared from non-infected and infected cells at various time points p.i., and real-time RT-PCR was performed to measure the levels of IFN-β (A and D) and viral S gene copy numbers (C and F). Cultural media of HepG2 cells were collected at various times points p.i. for ELISA to measure the concentration of IFN-β (B and E).

Mentions: We further examined the effect of viral NSs on the induction of antiviral IFN-β and viral replication. Twenty-four hours prior to SFTSV infection, HepG2 and HeLa cells were transfected either with the plasmid expressing NSs or the blanket plasmid. Total RNA was prepared from the cells after SFTSV infection and analyzed with realtime RT-PCR. We also analyzed the IFN-β concentration in the cultural media with or without overexpression of NSs. Our data indicate that induction of IFN-β was suppressed at both RNA and protein levels in the presence of NSs (Fig. 10A,B). Similar results were obtained in HeLa cells as shown in Fig. 10D,E. We also quantified the copy numbers of the viral S gene and detected significant increase of the S gene copy numbers in HepG2 (Fig. 10C) and HeLa cells (Fig. 10F), respectively. Taken together, our data demonstrate that viral NSs may function as a negative modulator of antiviral IFN-β induction and a promoter of viral replication in liver epithelial cells.


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)

Induction of IFN-β was suppressed by NSs.HepG2 (A, B and C) and HeLa (D, E and F) cells were transfected with cDNA expressing HA-tagged NSs or blank plasmid. After 24 hrs, the cells were mock infected or infected with SFTSV. Total RNA was prepared from non-infected and infected cells at various time points p.i., and real-time RT-PCR was performed to measure the levels of IFN-β (A and D) and viral S gene copy numbers (C and F). Cultural media of HepG2 cells were collected at various times points p.i. for ELISA to measure the concentration of IFN-β (B and E).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f10: Induction of IFN-β was suppressed by NSs.HepG2 (A, B and C) and HeLa (D, E and F) cells were transfected with cDNA expressing HA-tagged NSs or blank plasmid. After 24 hrs, the cells were mock infected or infected with SFTSV. Total RNA was prepared from non-infected and infected cells at various time points p.i., and real-time RT-PCR was performed to measure the levels of IFN-β (A and D) and viral S gene copy numbers (C and F). Cultural media of HepG2 cells were collected at various times points p.i. for ELISA to measure the concentration of IFN-β (B and E).
Mentions: We further examined the effect of viral NSs on the induction of antiviral IFN-β and viral replication. Twenty-four hours prior to SFTSV infection, HepG2 and HeLa cells were transfected either with the plasmid expressing NSs or the blanket plasmid. Total RNA was prepared from the cells after SFTSV infection and analyzed with realtime RT-PCR. We also analyzed the IFN-β concentration in the cultural media with or without overexpression of NSs. Our data indicate that induction of IFN-β was suppressed at both RNA and protein levels in the presence of NSs (Fig. 10A,B). Similar results were obtained in HeLa cells as shown in Fig. 10D,E. We also quantified the copy numbers of the viral S gene and detected significant increase of the S gene copy numbers in HepG2 (Fig. 10C) and HeLa cells (Fig. 10F), respectively. Taken together, our data demonstrate that viral NSs may function as a negative modulator of antiviral IFN-β induction and a promoter of viral replication in liver epithelial cells.

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