BMC Vet Res. 2020 Mar 3;16(1):72. doi: 10.1186/s12917-020-02291-w.
Beta-catenin inhibits bovine parainfluenza virus type 3 replication via innate immunity pathway
Xinying Du 1, Wenqi He 2, Hongbin He 3, Hongmei Wang 4
Background: Bovine parainfluenza virus type 3 (BPIV3) is one of the important viral respiratory agents associated with the bovine respiratory disease complex (BRDC) in cattle. Previous study has demonstrated that infection of BPIV3 causes innate immune response within the host cell. β-catenin is a key component of the Wnt/β-catenin signal pathway which is involved in the regulation of interferon-beta (IFN-β) transcription. Some viruses can activate while others can inhibit the Wnt/β-catenin signaling pathway. However, the role of β-catenin in BPIV3 infection remains unclear.
Results: Here we found that the expression of β-catenin mRNA was up-regulated and β-catenin protein was down-regulated after BPIV3 infection in MDBK cells. Moreover, it was confirmed that overexpression of β-catenin suppressed BPIV3 replication and knockdown of β-catenin promoted viral replication, suggesting that β-catenin inhibits BPIV3 replication. Furthermore, IFN-β signal pathway and virus titer analysis using the GSK3β inhibitor (LiCl) revealed that Wnt/β-catenin can serve as a mechanism to suppress virus replication in infected cells. The results indicated that LiCl promoted the expression and accumulation in the nucleus of β-catenin, which further promoted the expression of IFN-β and OSA1 and suppressed BPIV3 replication. Most importantly, BPIV3 down-regulating β-catenin protein expression was due to degradation of GSK3β mediated proteasome pathway.
Conclusions: In summary, we discovered the relationship between β-catenin and BPIV3 replication. These results provided further insight into the study of BPIV3 pathogenesis.
PLoS One. 2018; 13(1): e0191010.
Regulation of influenza virus replication by Wnt/β-catenin signaling
Sunil More, Conceptualization, Investigation, Writing – original draft,1,2 Xiaoyun Yang, Investigation,1,2 Zhengyu Zhu, Investigation,1,2 Gayan Bamunuarachchi, Investigation,1,2 Yujie Guo, Investigation,1,2 Chaoqun Huang, Investigation,1,2 Keith Bailey, Formal analysis,3,4 Jordan P. Metcalf, Writing – review & editing,2,5 and Lin Liu, Conceptualization, Funding acquisition, Project administration, Supervision, Writing – review & editing1,2,*
Wnt/β-catenin signaling is an essential pathway in cell cycle control. Dysregulation of the Wnt/β-catenin signaling pathway during viral infection has been reported. In this study, we examined the effect of modulating Wnt/β-catenin signaling during influenza virus infection. The activation of the Wnt/β-catenin pathway by Wnt3a increased influenza virus mRNA and virus production in in vitro in mouse lung epithelial E10 cells and mRNA expresson of influenza virus genes in vivo in the lungs of mice infected with influenza virus A/Puerto Rico/8/34. However, the inhibition of Wnt/β-catenin signaling by iCRT14 reduced virus titer and viral gene expression in human lung epithelial A549 cells and viral replication in primary mouse alveolar epithelial cells infected with different influenza virus strains. Knockdown of β-catenin also reduced viral protein expression and virus production. iCRT14 acts at the early stage of virus replication. Treatment with iCRT14 inhibited the expression of the viral genes (vRNA, cRNA and mRNA) evaluated in this study. The intraperitoneal administration of iCRT14 reduced viral load, improved clinical signs, and partially protected mice from influenza virus infection.
Antibodies (Basel). 2020 Sep; 9(3): 44.
CD47 as a Potential Target to Therapy for Infectious Diseases
Lamin B. Cham,* Tom Adomati, Fanghui Li, Murtaza Ali, and Karl S. Lang
The integrin associated protein (CD47) is a widely and moderately expressed glycoprotein in all healthy cells. Cancer cells are known to induce increased CD47 expression. Similar to cancer cells, all immune cells can upregulate their CD47 surface expression during infection. The CD47-SIRPa interaction induces an inhibitory effect on macrophages and dendritic cells (dendritic cells) while CD47-thrombospondin-signaling inhibits T cells. Therefore, the disruption of the CD47 interaction can mediate several biologic functions. Upon the blockade and knockout of CD47 reveals an immunosuppressive effect of CD47 during LCMV, influenza virus, HIV-1, mycobacterium tuberculosis, plasmodium and other bacterial pneumonia infections. In our recent study we shows that the blockade of CD47 using the anti-CD47 antibody increases the activation and effector function of macrophages, dendritic cells and T cells during viral infection. By enhancing both innate and adaptive immunity, CD47 blocking antibody promotes antiviral effect. Due to its broad mode of action, the immune-stimulatory effect derived from this antibody could be applicable in nonresolving and (re)emerging infections. The anti-CD47 antibody is currently under clinical trial for the treatment of cancer and could also have amenable therapeutic potential against infectious diseases. This review highlights the immunotherapeutic targeted role of CD47 in the infectious disease realm.