Interleukin-10 Promotes Porcine Circovirus Type 2 Persistent Infection in Mice and Aggravates the Tissue Lesions by Suppression of T Cell Infiltration

Du, Qian; Zhang, Huan; He, Mingrui; Zhao, Xuan; He, Jia; Cui, Beibei; Yang, Xuefeng; Tong, Dewen; Huang, Yong

doi:10.3389/fmicb.2019.02050

Cited by 6 publications

(6 citation statements)

References 34 publications

(42 reference statements)

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“…Moreover, as reported previously, IFN and IL-2 enhance PCV2 infection [3][4][5][6][7]. IL-10 promoted persistent infection of PCV2 and aggravated tissue damage by inhibiting T cell infiltration [42], which, in turn, leads to immunosuppression in persistent and chronic viral infection [42,43]. These results suggest porcine TRIM21 positively regulates immune responses during PCV2 infection, thus enhancing PCV2 replication.…”

Section: Discussionsupporting

confidence: 78%

Porcine TRIM21 Enhances Porcine Circovirus 2 Infection and Host Immune Responses, But Inhibits Apoptosis of PCV2-Infected Cells

Yang

Liu

Zhang

et al. 2022

Viruses

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Tripartite motif protein 21 (TRIM21) is an interferon-inducible E3 ligase, containing one RING finger domain, one B-box motif, one coiled-coil domain at the N-terminal, as well as one PRY domain and one SPRY domain at the C-terminal. TRIM21 is expressed in many tissues and plays an important role in systemic autoimmunity. However, TRIM21 plays different roles in different virus infections. In this study, we evaluate the relationship between porcine TRIM21 and PCV2 infection as well as host immune responses. We found that PCV2 infection modulated the expression of porcine TRIM21. TRIM21 can enhance interferons and proinflammatory factors and decrease cellular apoptosis in PCV2-infected cells. These results indicate that porcine TRIM21 plays a critical role in enhancing PCV2 infection, which is a promising target for controlling and developing the treatment of PCV2 infection.

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Section: Discussionsupporting

confidence: 78%

Porcine TRIM21 Enhances Porcine Circovirus 2 Infection and Host Immune Responses, But Inhibits Apoptosis of PCV2-Infected Cells

Yang

Liu

Zhang

et al. 2022

Viruses

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“…PCV2, as the most prevalent pathogen in global pig populations [ 60 ], leads to the infected pigs more susceptible to other pathogens [ 39 ]. Our previous studies have showed that PCV2 infection suppresses IL-12p40 expression to lower host Th1 immunity through the Cap and gC1qR interaction–mediated PI3K/Akt and p38 MAPK pathway and employs IL-10 to block the transfer of T cells, promotes the polarization of macrophage M2, and attenuates the production of pro-inflammatory cytokines [ 27 , 61 ]. These studies provide a new theory for explaining why PCV2 infection increases susceptibility to other pathogens.…”

Section: Discussionmentioning

confidence: 99%

PCV2 targets cGAS to inhibit type I interferon induction to promote other DNA virus infection

Wang

Chen

et al. 2021

PLoS Pathog

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Viruses use diverse strategies to impair the antiviral immunity of host in order to promote infection and pathogenesis. Herein, we found that PCV2 infection promotes the infection of DNA viruses through inhibiting IFN-β induction in vivo and in vitro. In the early phase of infection, PCV2 promotes the phosphorylation of cGAS at S278 via activation of PI3K/Akt signaling, which directly silences the catalytic activity of cGAS. Subsequently, phosphorylation of cGAS at S278 can facilitate the K48-linked poly-ubiquitination of cGAS at K389, which can been served as a signal for recognizing by the ubiquitin-binding domain of histone deacetylase 6 (HDAC6), to promote the translocation of K48-ubiquitinated-cGAS from cytosol to autolysosome depending on the deacetylase activity of HDAC6, thereby eventually resulting in a markedly increased cGAS degradation in PCV2 infection-induced autophagic cells relative to Earle’s Balanced Salt Solution (EBSS)-induced autophagic cells (a typical starving autophagy). Importantly, we found that PCV2 Cap and its binding protein gC1qR act as predominant regulators to promote porcine cGAS phosphorylation and HDAC6 activation through mediating PI3K/AKT signaling and PKCδ signaling activation. Based on this finding, gC1qR-binding activity deficient PCV2 mutant (PCV2RmA) indeed show a weakened inhibitory effect on IFN-β induction and a weaker boost effect for other DNA viruses infection compared to wild-type PCV2. Collectively, our findings illuminate a systematic regulation mechanism by which porcine circovirus counteracts the cGAS-STING signaling pathway to inhibit the type I interferon induction and promote DNA virus infection, and identify gC1qR as an important regulator for the immunosuppression induced by PCV2.

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“… 2015 ; Du et al. 2019 ). IL-10 supports PCV2 replication in the late phase of infection and the viral load correlates with the IL-10 level (Darwich et al.…”

Section: Molecular Background Of Il-10/il-12 Pathway Modulationsmentioning

confidence: 99%

“… 2008 ; Du et al. 2019 ). The IL-10 mRNA level has been shown to increase in the lymphoid tissues and has been related with the degree of lymphocyte depletion in the thymus of pigs with PCVAD (Darwich et al.…”

Section: Molecular Background Of Il-10/il-12 Pathway Modulationsmentioning

confidence: 99%

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Mechanisms of circovirus immunosuppression and pathogenesis with a focus on porcine circovirus 2: a review

Fehér

Jakab

Bányai

2023

Veterinary Quarterly

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Certain pathogens, due to their adverse effects on the immune reaction, aggravate the course of concomitant heterologous infections. Here we summarize mechanisms by which circoviruses, including the most studied porcine circovirus 2, and other mammalian and avian circoviruses, trigger their own replication and confound the hosts’ immune response. At different stages of infection, from latent state to disease induction, these viruses markedly influence the cellular signaling pathways. Circoviruses have been found to interfere with interferon and proinflammatory cytokine producing and responsive pathways. Apoptotic processes, altered cellular transport and constraint of the mitotic phase all support the viral replication. The cytokine imbalance and lymphocyte depletion, thus the impaired immunity, favors invasion of super- or co-infecting agents, which in concert with circoviruses induce illnesses with increased severity. The information summarized in this review point out the diversity of host and viral factors involved in the mechanisms of disease progression during circovirus infections.

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Interleukin-10 Promotes Porcine Circovirus Type 2 Persistent Infection in Mice and Aggravates the Tissue Lesions by Suppression of T Cell Infiltration

Cited by 6 publications

References 34 publications

Porcine TRIM21 Enhances Porcine Circovirus 2 Infection and Host Immune Responses, But Inhibits Apoptosis of PCV2-Infected Cells

Porcine TRIM21 Enhances Porcine Circovirus 2 Infection and Host Immune Responses, But Inhibits Apoptosis of PCV2-Infected Cells

PCV2 targets cGAS to inhibit type I interferon induction to promote other DNA virus infection

Mechanisms of circovirus immunosuppression and pathogenesis with a focus on porcine circovirus 2: a review

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