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Poly(I:C) induces antiviral immune responses in Japanese flounder (Paralichthys olivaceus) that require TLR3 and MDA5 and is negatively regulated by Myd88.

Zhou ZX, Zhang BC, Sun L - PLoS ONE (2014)

Bottom Line: We found that poly(I:C) exhibited strong antiviral activity and enhanced activation of head kidney macrophages and peripheral blood leukocytes.In vivo studies showed that (i) TLR3 as well as MDA5 knockdown reduced poly(I:C)-mediated immune response and antiviral activity to significant extents; (ii) when Myd88 was overexpressed in flounder, poly(I:C)-mediated antiviral activity was significantly decreased; (iii) when Myd88 was inactivated, the antiviral effect of poly(I:C) was significantly increased.These results provide insights to the working mechanism of poly(I:C), TLR3, and Myd88 in fish.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, China.

ABSTRACT
Polyinosinic:polycytidylic acid (poly(I:C)) is a ligand of toll-like receptor (TLR) 3 that has been used as an immunostimulant in humans and mice against viral diseases based on its ability to enhance innate and adapt immunity. Antiviral effect of poly(I:C) has also been observed in teleost, however, the underling mechanism is not clear. In this study, we investigated the potential and signaling mechanism of poly(I:C) as an antiviral agent in a model of Japanese flounder (Paralichthys olivaceus) infected with megalocytivirus. We found that poly(I:C) exhibited strong antiviral activity and enhanced activation of head kidney macrophages and peripheral blood leukocytes. In vivo studies showed that (i) TLR3 as well as MDA5 knockdown reduced poly(I:C)-mediated immune response and antiviral activity to significant extents; (ii) when Myd88 was overexpressed in flounder, poly(I:C)-mediated antiviral activity was significantly decreased; (iii) when Myd88 was inactivated, the antiviral effect of poly(I:C) was significantly increased. Cellular study showed that (i) the NF-κB activity induced by poly(I:C) was upregulated in Myd88-overexpressing cells and unaffected in Myd88-inactivated cells; (ii) Myd88 overexpression inhibited and upregulated the expression of poly(I:C)-induced antiviral genes and inflammatory genes respectively; (iii) Myd88 inactivation enhanced the expression of the antiviral genes induced by poly(I:C). Taken together, these results indicate that poly(I:C) is an immunostimulant with antiviral potential, and that the immune response of poly(I:C) requires TLR3 and MDA5 and is negatively regulated by Myd88 in a manner not involving NK-κB. These results provide insights to the working mechanism of poly(I:C), TLR3, and Myd88 in fish.

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Antiviral effect of poly(I:C) in Japanese flounder.Flounder pre-administered with or without (control) poly(I:C) were infected with megalocytivirus. The amounts of virus in kidney (A), spleen (B) and liver (C) were determined at 3 days (d), 5 d, and 7 d post-infection. Data are expressed as the mean ± SE (N = 3). N, the number of experimental repeat. *P<0.05; **P<0.01.
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pone-0112918-g001: Antiviral effect of poly(I:C) in Japanese flounder.Flounder pre-administered with or without (control) poly(I:C) were infected with megalocytivirus. The amounts of virus in kidney (A), spleen (B) and liver (C) were determined at 3 days (d), 5 d, and 7 d post-infection. Data are expressed as the mean ± SE (N = 3). N, the number of experimental repeat. *P<0.05; **P<0.01.

Mentions: To investigate the potential effect of poly(I:C) on viral replication in Japanese flounder, flounder were administered with or without poly(I:C) and then infected with megalocytivirus. At 3 days post-infection (dpi), 5 dpi, and 7 dpi, viral loads in kidney, spleen, and liver of the fish were examined. The results showed that treatment with poly(I:C) significantly reduced the number of virus in all examined tissues at all examined time points (Fig. 1).


Poly(I:C) induces antiviral immune responses in Japanese flounder (Paralichthys olivaceus) that require TLR3 and MDA5 and is negatively regulated by Myd88.

Zhou ZX, Zhang BC, Sun L - PLoS ONE (2014)

Antiviral effect of poly(I:C) in Japanese flounder.Flounder pre-administered with or without (control) poly(I:C) were infected with megalocytivirus. The amounts of virus in kidney (A), spleen (B) and liver (C) were determined at 3 days (d), 5 d, and 7 d post-infection. Data are expressed as the mean ± SE (N = 3). N, the number of experimental repeat. *P<0.05; **P<0.01.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4231074&req=5

pone-0112918-g001: Antiviral effect of poly(I:C) in Japanese flounder.Flounder pre-administered with or without (control) poly(I:C) were infected with megalocytivirus. The amounts of virus in kidney (A), spleen (B) and liver (C) were determined at 3 days (d), 5 d, and 7 d post-infection. Data are expressed as the mean ± SE (N = 3). N, the number of experimental repeat. *P<0.05; **P<0.01.
Mentions: To investigate the potential effect of poly(I:C) on viral replication in Japanese flounder, flounder were administered with or without poly(I:C) and then infected with megalocytivirus. At 3 days post-infection (dpi), 5 dpi, and 7 dpi, viral loads in kidney, spleen, and liver of the fish were examined. The results showed that treatment with poly(I:C) significantly reduced the number of virus in all examined tissues at all examined time points (Fig. 1).

Bottom Line: We found that poly(I:C) exhibited strong antiviral activity and enhanced activation of head kidney macrophages and peripheral blood leukocytes.In vivo studies showed that (i) TLR3 as well as MDA5 knockdown reduced poly(I:C)-mediated immune response and antiviral activity to significant extents; (ii) when Myd88 was overexpressed in flounder, poly(I:C)-mediated antiviral activity was significantly decreased; (iii) when Myd88 was inactivated, the antiviral effect of poly(I:C) was significantly increased.These results provide insights to the working mechanism of poly(I:C), TLR3, and Myd88 in fish.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, China.

ABSTRACT
Polyinosinic:polycytidylic acid (poly(I:C)) is a ligand of toll-like receptor (TLR) 3 that has been used as an immunostimulant in humans and mice against viral diseases based on its ability to enhance innate and adapt immunity. Antiviral effect of poly(I:C) has also been observed in teleost, however, the underling mechanism is not clear. In this study, we investigated the potential and signaling mechanism of poly(I:C) as an antiviral agent in a model of Japanese flounder (Paralichthys olivaceus) infected with megalocytivirus. We found that poly(I:C) exhibited strong antiviral activity and enhanced activation of head kidney macrophages and peripheral blood leukocytes. In vivo studies showed that (i) TLR3 as well as MDA5 knockdown reduced poly(I:C)-mediated immune response and antiviral activity to significant extents; (ii) when Myd88 was overexpressed in flounder, poly(I:C)-mediated antiviral activity was significantly decreased; (iii) when Myd88 was inactivated, the antiviral effect of poly(I:C) was significantly increased. Cellular study showed that (i) the NF-κB activity induced by poly(I:C) was upregulated in Myd88-overexpressing cells and unaffected in Myd88-inactivated cells; (ii) Myd88 overexpression inhibited and upregulated the expression of poly(I:C)-induced antiviral genes and inflammatory genes respectively; (iii) Myd88 inactivation enhanced the expression of the antiviral genes induced by poly(I:C). Taken together, these results indicate that poly(I:C) is an immunostimulant with antiviral potential, and that the immune response of poly(I:C) requires TLR3 and MDA5 and is negatively regulated by Myd88 in a manner not involving NK-κB. These results provide insights to the working mechanism of poly(I:C), TLR3, and Myd88 in fish.

Show MeSH
Related in: MedlinePlus