Porcine reproductive and respiratory syndrome virus(PRRSV) shows characteristic antibody-dependent enhancement(ADE) of infection and causes porcine systemic inflammation, which is similar to a type I allergic reaction...Porcine reproductive and respiratory syndrome virus(PRRSV) shows characteristic antibody-dependent enhancement(ADE) of infection and causes porcine systemic inflammation, which is similar to a type I allergic reaction; however, the role of porcine FceεRI in ADE is still unclear. In this study, the expression of different Fc receptors(Fc Rs) on macrophages was investigated in a PRRSV 3D4/21 cell infection model in the presence or absence of PRRSV antibody. The transcription level of Fcc II and FceεRI was significantly up-regulated under PRRSV-antibody complex infection. Internalization and proliferation of PRRSV were promoted by the ADE mechanism when FceεRI was expressed in permissive 3D4/21 cells and the non-permissive cell line HEK 293T. Transcriptome sequencing data showed that the expression levels of AKT,ERK and other signal molecules in the anti-inflammatory pathway were significantly increased, especially in the cells infected with the PRRSV-antibody immune complex. Inflammatory regulatory molecules such as PLA2G6, LOX, TRPM8 and TRPM4 were significantly up-regulated following PRRSV infection but significantly down-regulated in the cells infected with the PRRSV-antibody immune complex. Our results demonstrated that FceεRI could be involved in PRRSV ADE, the antigen presenting process and regulation of the inflammatory response during PRRSV infection, which provides new insights into PRRSV infection mediated by FceεRI and the PRRSV-antibody immune complex.展开更多
Porcine reproductive and respiratory syndrome(PRRS) is an important infectious disease caused by porcine reproductive and respiratory syndrome virus(PRRSV), leading to significant economic losses in swine industry wor...Porcine reproductive and respiratory syndrome(PRRS) is an important infectious disease caused by porcine reproductive and respiratory syndrome virus(PRRSV), leading to significant economic losses in swine industry worldwide. Although several studies have shown that PRRSV can affect the cell cycle of infected cells, it is still unclear how it manipulates the cell cycle to facilitate its proliferation. In this study, we analyzed the mRNA expression profiles of transcription factors in PRRSV-infected 3D4/21 cells by RNA-sequencing. The result shows that the expression of transcription factor DP2(TFDP2) is remarkably upregulated in PRRSV-infected cells. Further studies show that TFDP2 contributes to PRRSV proliferation and the PRRSV nucleocapsid(N) protein induces TFDP2 expression by activating C/EBPb. TFDP2 positively regulates cyclin A expression and triggers a less proportion of cells in the S phase, which contributes to PRRSV proliferation. This study proposes a novel mechanism by which PRRSV utilizes host protein to regulate the cell cycle to favor its infection. Findings from this study will help us for a better understanding of PRRSV pathogenesis.展开更多
To the Editor:Bullous pemphigoid(BP)is a rare autoimmune skin disorder characterized by significant mortality,with BP prevalence ranging from 1.46 to 47.99 cases per 100,000 people.[1]The pathogenic mechanism of BP is...To the Editor:Bullous pemphigoid(BP)is a rare autoimmune skin disorder characterized by significant mortality,with BP prevalence ranging from 1.46 to 47.99 cases per 100,000 people.[1]The pathogenic mechanism of BP is attributed to pathogenic autoantibodies targeting BP180 and BP230 antigens,resulting in the formation of subepidermal blisters.[1]Reports indicate that some BP patients also have circulating anti-desmoglein(Dsg)autoantibodies,which are pathogenic antibodies in pemphigus.[2]However,it remains uninvestigated whether the concomitant anti-Dsg antibodies in BP are pathogenic and thereby represent a coincidental occurrence or signify the coexistence of the two diseases.This knowledge gap introduces uncertainty in patient care management.Therefore,a comprehensive analysis was performed to explore the clinicohistopathological characteristics,human leukocyte antigen(HLA)genetic risk factors,and pathogenicity of anti-Dsg antibodies in BP patients with anti-Dsg antibodies compared to those without.展开更多
基金supported by the National Natural Science Foundation of China (31272540)the underprop project of Tianjin Science and Technology Committee in China (16YFZCNC00640)
文摘Porcine reproductive and respiratory syndrome virus(PRRSV) shows characteristic antibody-dependent enhancement(ADE) of infection and causes porcine systemic inflammation, which is similar to a type I allergic reaction; however, the role of porcine FceεRI in ADE is still unclear. In this study, the expression of different Fc receptors(Fc Rs) on macrophages was investigated in a PRRSV 3D4/21 cell infection model in the presence or absence of PRRSV antibody. The transcription level of Fcc II and FceεRI was significantly up-regulated under PRRSV-antibody complex infection. Internalization and proliferation of PRRSV were promoted by the ADE mechanism when FceεRI was expressed in permissive 3D4/21 cells and the non-permissive cell line HEK 293T. Transcriptome sequencing data showed that the expression levels of AKT,ERK and other signal molecules in the anti-inflammatory pathway were significantly increased, especially in the cells infected with the PRRSV-antibody immune complex. Inflammatory regulatory molecules such as PLA2G6, LOX, TRPM8 and TRPM4 were significantly up-regulated following PRRSV infection but significantly down-regulated in the cells infected with the PRRSV-antibody immune complex. Our results demonstrated that FceεRI could be involved in PRRSV ADE, the antigen presenting process and regulation of the inflammatory response during PRRSV infection, which provides new insights into PRRSV infection mediated by FceεRI and the PRRSV-antibody immune complex.
基金This work was supported by the National Key Research and Development Program of China(2018YFD0500500)the National Natural Science Foundation of China(31272540)。
文摘Porcine reproductive and respiratory syndrome(PRRS) is an important infectious disease caused by porcine reproductive and respiratory syndrome virus(PRRSV), leading to significant economic losses in swine industry worldwide. Although several studies have shown that PRRSV can affect the cell cycle of infected cells, it is still unclear how it manipulates the cell cycle to facilitate its proliferation. In this study, we analyzed the mRNA expression profiles of transcription factors in PRRSV-infected 3D4/21 cells by RNA-sequencing. The result shows that the expression of transcription factor DP2(TFDP2) is remarkably upregulated in PRRSV-infected cells. Further studies show that TFDP2 contributes to PRRSV proliferation and the PRRSV nucleocapsid(N) protein induces TFDP2 expression by activating C/EBPb. TFDP2 positively regulates cyclin A expression and triggers a less proportion of cells in the S phase, which contributes to PRRSV proliferation. This study proposes a novel mechanism by which PRRSV utilizes host protein to regulate the cell cycle to favor its infection. Findings from this study will help us for a better understanding of PRRSV pathogenesis.
基金supported by grants from the Central Guidance for Local Scientific and Technological Development Projects of Shandong Province(No.YDZX2023058)the Shandong Province Taishan Scholar Project(No.tsqn201909141).
文摘To the Editor:Bullous pemphigoid(BP)is a rare autoimmune skin disorder characterized by significant mortality,with BP prevalence ranging from 1.46 to 47.99 cases per 100,000 people.[1]The pathogenic mechanism of BP is attributed to pathogenic autoantibodies targeting BP180 and BP230 antigens,resulting in the formation of subepidermal blisters.[1]Reports indicate that some BP patients also have circulating anti-desmoglein(Dsg)autoantibodies,which are pathogenic antibodies in pemphigus.[2]However,it remains uninvestigated whether the concomitant anti-Dsg antibodies in BP are pathogenic and thereby represent a coincidental occurrence or signify the coexistence of the two diseases.This knowledge gap introduces uncertainty in patient care management.Therefore,a comprehensive analysis was performed to explore the clinicohistopathological characteristics,human leukocyte antigen(HLA)genetic risk factors,and pathogenicity of anti-Dsg antibodies in BP patients with anti-Dsg antibodies compared to those without.
