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. 2024 Oct 22:14:1452158.
doi: 10.3389/fcimb.2024.1452158. eCollection 2024.

Apoptosis, inflammatory and innate immune responses induced by infection with a novel goose astrovirus in goose embryonic kidney cells

Affiliations

Apoptosis, inflammatory and innate immune responses induced by infection with a novel goose astrovirus in goose embryonic kidney cells

Zhanpeng Hou et al. Front Cell Infect Microbiol. .

Abstract

Introduction: Since 2016, a highly lethal visceral gout induced by infection with the novel goose astrovirus (GoAstV) resulted in an ongoing outbreak in goslings in China, with a mortality rate ranging from 10% to 50%, and causing considerable economic losses in the goose industry. However, the pathogenesis of GoAstV and the molecular mechanism by which kidney lesions are induced by GoAstV infection are unclear.

Methods: In the present study, a GEK cell infection model for GoAstV was established, and the apoptosis, inflammatory and innate immune responses induced by GoAstV were investigated in GEK cells.

Results: The results shown that the expression of proapoptotic proteins, including Bax, caspase-3, caspase-9 and cytochrome c, increased in the infection group; however, the expression of the antiapoptotic protein Bcl-2 decreased, indicating that apoptosis was induced by GoAstV infection in GEK cells. Besides, the activation of the RIG-I/MDA5 pathway and the downstream upregulation of proinflammatory cytokines, including the adapter proteins MAVS, IRF7 and NF-κB and the proinflammatory cytokines IL-6, IL-8 and TNF-α, were detected in GEK cells infected with GoAstV. In addition, GoAstV infection induces the activation of the NLPR3 pathway and further stimulates the increased production of IL-1β. In summary, the present study revealed that GoAstV infection could induce apoptosis and the activation of the RIG-I/MDA5 and NLRP3 pathways in GEK cells, as well as the massive release of proinflammatory cytokines.

Discussion: These results are helpful for elucidating the molecular mechanism of pathological lesions in the kidney in gout goslings infected with GoAstV and the interaction between GoAstV and the innate immune system of the host.

Keywords: GoAstV; NLRP3; apoptosis; inflammatory response; innate immune.

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Conflict of interest statement

The authors declare the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
GEK cells infected with GoAstV were identified by indirect immunofluorescence at 48 hours post infection.
Figure 2
Figure 2
Apoptosis induced by GoAstV infection in GEK cells. (A) The mRNA expression levels of Bax, Bcl-2, Caspase-3 and Caspase-9 at 12 hpi, 24 hpi and 48 hpi. (B) The protein expression levels of Bax, Bcl-2, cleaved caspase-3, cleaved caspase-9 and cytochrome c (Cyt c), which are responsible for mitochondrial apoptosis, in GEK cells infected with GoAstV at 12 hpi, 24 hpi and 48 hpi. (C) The histogram summarizes the protein expression levels. **, p < 0.01; ***, p < 0.001.
Figure 3
Figure 3
The activation of the RIG-I/MDA5 pathway and inflammatory cytokine expression induced by GoAstV infection. (A) The mRNA expression levels of genes involved in the RIG-I/MDA5 pathway (RIG-I, MDA5, MAVS, IRF7 and NF-κB) and inflammatory cytokines (IL-6, IL-8 and TNF-α) in GEK cells infected with GoAstV at 12 hpi, 24 hpi and 48 hpi. (B) The protein expression levels of genes involved in the RIG-I/MDA5 pathway (MDA5, MAVS, IRF7 and pNF-κB) and inflammatory cytokines (IL-6 and TNF-α) in GEK cells infected with GoAstV at 12 hpi, 24 hpi and 48 hpi. (C) The histogram summarizes the protein expression levels. *, p < 0.05; **, p < 0.01; ***, p < 0.001.
Figure 4
Figure 4
Activation of NLRP3 induced by GoAstV infection in GEK cells. (A) The mRNA expression levels of NLRP3, Caspase-1 and IL-1β in GEK cells infected with GoAstV at 12 hpi, 24 hpi and 48 hpi. (B) The protein expression levels of NLRP3, cleaved caspase-1 and IL-1β in GEK cells infected with GoAstV at 12 hpi, 24 hpi and 48 hpi. (C) The histogram summarizes the protein expression levels. **, p < 0.01; ***, p < 0.001.

References

    1. Allen I. C., Scull M. A., Moore C. B., Holl E. K., McElvania-TeKippe E., Taxman D. J., et al. . (2009). The NLRP3 inflammasome mediates in vivo innate immunity to influenza A virus through recognition of viral RNA. Immunity 30, 556–565. doi: 10.1016/j.immuni.2009.02.005 - DOI - PMC - PubMed
    1. An D., Zhang J., Yang J., Tang Y., Diao Y. (2020). Novel goose-origin astrovirus infection in geese: the effect of age at infection. Poultry Sci. 99, 4323–4333. doi: 10.1016/j.psj.2020.05.041 - DOI - PMC - PubMed
    1. Chu J. H., Li L. X., Gao P. C., Chen X. W., Wang Z. Y., Fan R. F. (2022). Mercuric chloride induces sequential activation of ferroptosis and necroptosis in chicken embryo kidney cells by triggering ferritinophagy. Free Radical Biol. Med. 188, 35–44. doi: 10.1016/j.freeradbiomed.2022.06.002 - DOI - PubMed
    1. Danthi P. (2016). Viruses and the diversity of cell death. Annu. Rev. Virol. 3, 533–553. doi: 10.1146/annurev-virology-110615-042435 - DOI - PubMed
    1. DeBiasi R. L., Robinson B. A., Sherry B., Bouchard R., Brown R. D., Rizeq M., et al. . (2004). Caspase inhibition protects against reovirus-induced myocardial injury in vitro and in vivo . J. Virol. 78, 11040–11050. doi: 10.1128/JVI.78.20.11040-11050.2004 - DOI - PMC - PubMed

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