Canine Distemper Virus Utilizes Different Receptors to Infect Chicken Embryo Fibroblasts and Vero cells

Inducing animal viruses to adapt to chicken embryos or chicken embryo fibroblasts(CEF) is a common method to develop attenuated live vaccines with full security.Canine distemper virus(CDV) also does this,but the mechanisms and particular receptors remain unclear.Virus overlay protein blot assays were carried out on CEF membrane proteins,which were extracted respectively with a Mem-PER TM kit,a radioimmunoprecipitation assay buffer or a modified co-immunoprecipitation method,and revealed a common 57 kDa positive band that differed from the 42-kDa positive band in Vero cells and also from those receptors reported in lymphocytes and 293 cells,indicating a receptor diversity of CDV and the possibility of the 57-kDa protein acting as a receptor that is involved in adaptive infection of CDV Kunming strain to CEF.

Tim-3 promotes cell aggressiveness and paclitaxel resistance through NF-κB/STAT3 signalling pathway in breast cancer cells

Objective:Although T-cell immunoglobulin and mucin-domain containing molecule-3(Tim-3)has been recognized as a promising target for cancer immunotherapy,its exact role in breast cancer has not been fully elucidated.Methods:Tim-3 gene expression in breast cancer and its prognostic significance were analyzed.Associated mechanisms were then explored in vitro by establishing Tim-3-overexpressing breast cancer cells.Results:In a pooled analysis of The Cancer Genome Atlas(TCGA)database,Tim-3 gene expression levels were significantly higher(P<0.001)in breast cancer tissue,compared with normal tissues.Tim-3 was a prognosis indicator in breast cancer patients[relapse-free survival(RFS),P=0.004;overall survival(OS),P=0.099].Tim-3 overexpression in Tim-3 low breast cancer cells promoted aggressiveness of breast cancer cells,as evidenced by enhanced proliferation,migration,invasion,tight junction deterioration and tumor-associated tubal formation.Tim-3 also enhanced cellular resistance to paclitaxel.Furthermore,Tim-3 exerted its function by activating the NF-κB/STAT3 signalling pathway and by regulating gene expression[cyclin D1(CCND1),C-Myc,matrix metalloproteinase-1(MMP1),TWIST,vascular endothelial growth factor(VEGF)upregulation,concomitant with Ecadherin downregulation).Lastly,Tim-3 downregulated tight junction-associated molecules zona occludens(ZO)-2,ZO-1 and occludin,which may further facilitate tumor progression.Conclusions:Tim-3 plays an oncogenic role in breast cancer and may represent a potential target for antitumor therapy.

Integrin Activation and Viral Infection

Integrins are members of a ubiquitous membrane receptor family which includes 18 different α subunits and 8 β subunits forming more than 20 α/β heterodimers. Integrins play key functions in vascular endothelial cell and tumour cell adhesion, lymphocyte trafficking, tumor growth and viral infection. Current understanding of the molecular basis of integrins as viral receptors has been achieved through many decades of study into the biology of transmembrane glycoproteins and their interactions with several viruses. This review provides a summary of the current knowledge on the molecular bases of interactions between viruses and integrins, which are of potential practical significance. Inhibition of virus-integrin interactions at the points of virus attachment or entry will provide a novel approach for the therapeutic treatment of viral diseases.

Structure-activity relationship of cyclic ADP-ribose, an update

Cyclic ADP-ribose (cADPR) is a universal Ca2+ mobilizing second messenger in many different cell types and organisms. cADPR activates Ca2+ release from endo/sarcoplasmic reticulum via ryanodine receptors. In addition, Ca2+ entry secondary to Ca2+ depletion is at least one of the mechanisms in which cADPR triggers Ca2+ inflow, too. Analogues of cADPR have been prepared by chemical and chemo-enzymatic routes. Most of the analogues were analyzed for biological activity in intact or permeabilized Jurkat T cells (a human T-lymphoma cell line). As a systematic approach, analogues were grouped according to alterations in the base, the northern ribose, the southern ribose, the pyrophosphate backbone, or in complex modifications, comprising more than one part of the molecule. Biological activity of the analogues is reviewed, with special emphasis on Jurkat T cells.