Activation of activating Fc gamma receptors down-regulates the levels of interferon β, interferon γ and interferon λ1 in porcine alveolar macrophages during PRRSV infection

Zhang, Liujun; Wen, Li; Sun, Yangyang; Li, Xiangtong; Kong, Linghao; Xu, Pengli; Xia, Pingan; Yue, Junming

doi:10.1016/j.intimp.2020.106268

Cited by 3 publications

(3 citation statements)

References 40 publications

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“…Rig-I receptors activate and upregulate the expression of the sepsis proinflammatory factor IFN-β [ [27] , [28] , [29] ], so inhibition of the IRF3 signaling pathway may reduce the inflammatory response in sepsis [ 30 ]. In this study, compared with the control group, the ANKRD22 overexpression group exhibited increased IFN-β secretion in macrophages, with or without the induction of poly (I:C).…”

Section: Resultsmentioning

confidence: 99%

ANKRD22 aggravates sepsis-induced ARDS and promotes pulmonary M1 macrophage polarization

Zhang,

Liu,

Zhang

et al. 2024

Journal of Translational Autoimmunity

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Section: Resultsmentioning

confidence: 99%

ANKRD22 aggravates sepsis-induced ARDS and promotes pulmonary M1 macrophage polarization

Zhang,

Liu,

Zhang

et al. 2024

Journal of Translational Autoimmunity

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“…Significantly, our results showed that the expression of six major adaptor molecules (Myd88, IRAK2, IRAK4, TRAF3, TBK-1 and IRF7) downstream of RNA sensors were dramatically decreased in the PAMs with a PRRSV-ADE infection. Meanwhile, the studies of Zhang et al and Bao et al showed that a PRRSV-ADE infection could inhibit the production of IFN-α, IFN-β, IFN-λ and TNF-α [ 6 , 7 , 21 ]. Thus, these results demonstrated that a PRRSV-ADE infection might roundly inhibit the pattern recognition receptor (PRR)-mediated innate immune signals to facilitate a viral proliferation through multiple strategies.…”

Section: Discussionmentioning

confidence: 99%

“…MMP-9 can facilitate virus replication through intercept IFN/JAK-STAT signals [ 22 ]. Meanwhile, multiple studies reported that the IFN signals were dramatically down-regulated during the PRRSV-ADE infection [ 6 , 7 , 21 ]. It indicates that a PRRSV-ADE infection may have inhibited the JAK-STAT signals to block the expression of antiviral proteins by various ways.…”

Section: Discussionmentioning

confidence: 99%

Proteomic Characterization of PAMs with PRRSV-ADE Infection

Zhao

et al. 2022

Viruses

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The antibody-dependent enhancement (ADE) effect of a PRRSV infection is that the preexisting sub- or non-neutralizing antibodies specific against PRRSV can facilitate the virus entry and replication, and it is likely to be a great obstacle for the selection of immune strategies and the development of high-efficiency PRRSV vaccines. However, the proteomic characterization of primary alveolar macrophages (PAMs) with a PRRSV-ADE infection has not yet been investigated so far. Therefore, we performed a tandem mass tag (TMT)-based quantitative proteomic analysis of PAMs with a PRRSV-ADE infection in this study. The results showed that a total of 3935 differentially expressed proteins (DEPs) were identified in the PAMs infected with PRRSV-ADE, including 2004 up-regulated proteins and 1931 down-regulated proteins. Further, the bioinformatics analysis for these DEPs revealed that a PRRSV-ADE infection might disturb the functions of ribosome, proteasome and mitochondria. Interestingly, we also found that the expression of the key molecules in the innate immune pathways and antiviral proteins were significantly down-regulated during a PRRSV-ADE infection. This study was the first attempt to analyze the proteomic characterization of PAMs with a PRRSV-ADE infection in vitro. Additionally, the findings will provide valuable information for a better understanding of the mechanism of virus–antibody–host interactions during a PRRSV-ADE infection.

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Nanobody Nb6 fused with porcine IgG Fc as the delivering tag to inhibit porcine reproductive and respiratory syndrome virus replication in porcine alveolar macrophages

Zhang

Wang

Cao

et al. 2021

Vet Res

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Porcine reproductive and respiratory syndrome virus (PRRSV) is a highly contagious virus that has led to enormous economic loss worldwide because of ineffective prevention and treatment. In view of their minimized size, high target specificity and affinity, nanobodies have been extensively investigated as diagnostic tools and treatments of many diseases. Previously, a PRRSV Nsp9-specific nanobody (Nb6) was identified as a PRRSV replication inhibitor. When it was fused with cell-penetrating peptide (CPP) TAT, Nb6-TAT could enter the cells for PRRSV suppression. However, delivery of molecules by CPP lack cell specificity and have a short duration of action. PRRSV has a tropism for monocyte/macrophage lineage, which expresses high levels of Fcγ receptors. Herein, we designed a nanobody containing porcine IgG Fc (Fcγ) to inhibit PRRSV replication in PRRSV permissive cells. Fcγ fused Nb6 chimeric antibody (Nb6-pFc) was assembled into a dimer with interchain disulfide bonds and expressed in a Pichia pastoris system. The results show that Nb6-pFc exhibits a well-binding ability to recombinant Nsp9 or PRRSV-encoded Nsp9 and that FcγR-mediated endocytosis of Nb6-pFc into porcine alveolar macrophages (PAM) was in a dose-dependent manner. Nb6-pFc can inhibit PRRSV infection efficiently not only by binding with Nsp9 but also by upregulating proinflammatory cytokine production in PAM. Together, this study proposes the design of a porcine IgG Fc-fused nanobody that can enter PRRSV susceptible PAM via FcγR-mediated endocytosis and inhibit PRRSV replication. This research reveals that nanobody-Fcγ chimeric antibodies might be effective for the control and prevention of monocyte/macrophage lineage susceptible pathogeneses.

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Activation of activating Fc gamma receptors down-regulates the levels of interferon β, interferon γ and interferon λ1 in porcine alveolar macrophages during PRRSV infection

Cited by 3 publications

References 40 publications

ANKRD22 aggravates sepsis-induced ARDS and promotes pulmonary M1 macrophage polarization

ANKRD22 aggravates sepsis-induced ARDS and promotes pulmonary M1 macrophage polarization

Proteomic Characterization of PAMs with PRRSV-ADE Infection

Nanobody Nb6 fused with porcine IgG Fc as the delivering tag to inhibit porcine reproductive and respiratory syndrome virus replication in porcine alveolar macrophages

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