A case-control study on association between OAS1 polymorphism and susceptibility to spontaneous preterm birth and preterm premature rupture of membranes / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the association between the genetic polymorphism of 2',5'-oligoadenylate synthetase 1 (OAS1) and susceptibility to spontaneous preterm birth (SPTB) and preterm premature rupture of membranes (PPROM).</p><p><b>METHODS</b>The case-control study consisted of 599 preterm infants including 171 cases of PPROM, and 673 full-term infants without maternal histories of SPTB and PPROM as controls. The single nucleotide polymorphism (SNP) at OAS1 intron 5, rs10774671, was analyzed by polymerase chain reaction-restriction fragment length polymorphism.</p><p><b>RESULTS</b>No significant differences were observed between the case and control groups in the frequencies of genotypes (AA, GA, and GG) and alleles (A and G) of OAS1 rs10774671. When the case group was divided into two subgroups with or without PPROM, no significant differences in the genotype and allele frequencies were found between each subgroup and the control group. When the case group was divided into three subgroups with different gestational ages at SPTB, no significant differences in the genotype and allele frequencies were detected between each subgroup and the control group.</p><p><b>CONCLUSIONS</b>No association is identified between OAS1 SNP and susceptibility to SPTB and PPROM.</p>

Oligoadenylate synthase-like (OASL) proteins: dual functions and associations with diseases

The study of antiviral pathways to reveal methods for the effective response and clearance of virus is closely related to understanding interferon (IFN) signaling and its downstream target genes, IFN-stimulated genes. One of the key antiviral factors induced by IFNs, 2'-5' oligoadenylate synthase (OAS), is a well-known molecule that regulates the early phase of viral infection by degrading viral RNA in combination with RNase L, resulting in the inhibition of viral replication. In this review, we describe OAS family proteins from a different point of view from that of previous reviews. We discuss not only RNase L-dependent (canonical) and -independent (noncanonical) pathways but also the possibility of the OAS family members as biomarkers for various diseases and clues to non-immunological functions based on recent studies. In particular, we focus on OASL, a member of the OAS family that is relatively less well understood than the other members. We will explain its anti- and pro-viral dual roles as well as the diseases related to single-nucleotide polymorphisms in the corresponding gene.

Cloning, expression and functional analysis of the duck Toll-like receptor 5 (TLR5) gene

Toll-like receptor 5 (TLR5) is responsible for the recognition of bacterial flagellin in vertebrates. In the present study, the first TLR5 gene in duck was cloned. The open reading frame (ORF) of duck TLR5 (dTLR5) cDNA is 2580 bp and encodes a polypeptide of 859 amino acids. We also cloned partial sequences of myeloid differentiation factor 88, 2'-5'-oligoadenylate synthetase (OAS), and myxovirus resistance (Mx) genes from duck. dTLR5 mRNA was highly expressed in the bursa of Fabricius, spleen, trachea, lung, jejunum, rectum, and skin; moderately expressed in the muscular and glandular tissues, duodenum, ileum, caecum, and pancreas; and minimally expressed in the heart, liver, kidney, and muscle. DF-1 or HeLa cells transfected with DNA constructs encoding dTLR5 can activate NF-kappaB leading to the activation of interleukin-6 (IL-6) promoter. When we challenged ducks with a Herts33 Newcastle disease virus (NDV), mRNA transcription of the antiviral molecules Mx, Double stranded RNA activated protein kinase (PKR), and OAS was up-regulated in the liver, lung, and spleen 1 and 2 days post-inoculation.

The influence of HBV and its antigens on the expressions of JAK-STAT signal transduction pathway molecules and antiviral proteins of IFN alpha / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the possible influence of HBV and its antigens on the expressions of JAK-STAT signal transduction pathway molecules and the antiviral proteins of IFN alpha.</p><p><b>METHODS</b>The HepG2 cells were transfected with pSM2, pHBS2-S and pHBc-EGFP plasmids which express HBV whole particles or S-antigen, Pre-S antigen and core antigens. The infectious supernatant from HepG2.2.15 cells and the pured HBV proteins which contained the S, Pre-S antigens were used to treat the HepG2 cells. Northern blot and RT-PCR were applied to analyse the expressions of the antiviral proteins MxA, 2' -5' OAS, 9-27 and the JAK-STAT signal transduction pathway molecules STAT1 in HepG2 cells responded to the IFN alpha treatment.</p><p><b>RESULTS</b>The HepG2 cells transfected with pSM2, pHBS2-S and pHBc-EGFP plasmids could express whole HBV particles and HBsAg, Pre-S antigen and HBcAg. The quantitation of expressed HBV particles and antigens increased significantly during the course of transfection. Northern blot hybridization analysis indicated that the HepG2 cells expressed IFN alpha antiviral proteins MxA, 2' -5' OAS and 9-27. When transfected with pHBV-dimer, pHBS2-S, pHBc-EGFP plasmids, the IFN/A antiviral proteins MxA, 2' -5' OAS and 9-27 in transfected cells were reduced greatly as compared to the un-transfected HepG2 cells, and the expressed antiviral proteins decreased sharply with the development of transfection time. Furthermore, the expression of IFN alpha JAK-STAT signal transduction pathway molecule STAT1 was also inhibited with the expression of HBV particles and HBV antigens in transfected HepG2 cells.</p><p><b>CONCLUSIONS</b>The HBV and its antigens influence the expressions of IFN alpha JAK-STAT signal transduction pathway molecules and antiviral proteins in the hepatocellular models in vitro. It is indicated that HBV might possess the activity to antagonise or counteract the IFN alpha antiviral action.</p>

Relationship between SNP rs10774671 on OAS-1 gene and spontaneous HBeAg seroconversion in chronic HBV infection / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between the SNP rs10774671 on OAS-1 gene and spontaneous HBeAg seroconversion in chronic HBV infection.</p><p><b>METHODS</b>Blood samples were collected from 58 HBeAg positive, 68 anti-HBe positive patients with chronic HBV infection, and 72 normal control cases without HBV infection. Chromosomal DNA was extracted and OAS-1 gene was amplified. SNP genotyping was performed with the competitively differentiated polymerase chain reaction and enzyme immunoassay.</p><p><b>RESULTS</b>In HBeAg positive group, frequencies of genotype GG plus GA and allele G were 31.0% and 16.4%. They were 48.5% and 29.4% in anti-HBe positive group, and 50.0% and 28.4% in normal control group respectively. Differences between HBeAg positive group and anti-HBe positive group or normal control group were statistically significant. But they weren't between anti-HBe positive group and normal control group.</p><p><b>CONCLUSION</b>Allele G on SNP rs10774671 of OAS-1 gene maybe benefits patients with chronic HBV infection to achieve spontaneous HBeAg seroconversion. Genotyping on this SNP may be predicting valuable for interferon therapy for chronic HBV infection.</p>

Study of the effect of hepatitis C virus core protein on interferon-induced antiviral genes expression and its mechanisms / 生物工程学报

To study the effect of HCV core protein on the interferon-induced antiviral genes expression and its mechanisms. Methods HepG2 cells were transiently transfected with HCV core protein expression plasmid and the blank plasmid respectively. RT-PCR was used to analyze the effect of HCV core protein on PKR and 2'-5'OAS expression. The effect of HCV core protein on ISRE-medicated gene expression was detected by luciferase activity assay. Western-blot assay was performed to observe the change of mRNA and protein levels of SOCS3, STAT1 and p-STAT1 following HCV core expression. In the presence of HCV core protein, the transcription of PKR and 2'-5' OAS are down-regulated. ISRE-medicated reporter gene expression and STAT1 phosphorylation were inhibited. The transcription and expression of SOCS3 were induced compared with blank plasmid-transfected group. In HepG2 cells, HCV core protein can down-regulate the expression of some interferon-induced antiviral genes, which involves the induction of SOCS3 and the inhibition of STAT1 phosphorylation.

The Expression of TLR3 and Cytokines Induced by Poly I:C in Human Retinal Pigment Epithelial Cells

In this study, we examined the expression of Toll-like receptor3 (TLR3) by human retinal pigment epithelial cells (RPE) and determined whether exposure to the TLR3 agonist polyinosinic-polycytidylic acid (poly I:C) would induced the expression of cytokines in these cells. RT-PCR revealed that TLR3 was constitutively expressed in human RPE, and its expression was increased by treatment with poly I:C. After treatment with poly I:C, we determined the expression levels of pro-inflammatory cytokines in human RPE using RT-PCR and ELISA. We demonstrated that poly I:C treatment increased the production of TNF-alpha, IL-6, and IL-8 in human RPE. Upon exposure to poly I:C, human RPE initiated antiviral response resulting in the induction of IFN-beta mRNA expression and 2',5'-oligoadenylate synthetase mRNA expression. These results suggest that human RPE may participate in ocular defense mechanism against viral infection through TLR3.

Diferenciación de infecciones virales de bacterianas por medición de actividad de la enzima 2'-5' oligoadenilato sintetasa en células mononucleares de sangre periférica / Diferentiation of viral and bacterial infections by mesurement of 2'-5' oligoadenilate sintetase enzime activity sintetasa mononuclear cells of peripheric blood

Se describe el ensayo de laboratorio y uso de la enzima 2'-5' oligoadenilato sintetasa (2'-5' OAS) en el diagnóstico diferencial de infecciones virales de infecciones bacterianas. La enzima 2'-5' OAS se ensayó en extractos solubles de linfocitos de sangre periférica en 73 pacientes: 28 controles, 11 pacientes con infección bacteriana aguda confirmada y 34 pacientes con infecciones virales, documentadas por el cuadro clínico y/o de laboratorio. La actividad de la enzima 2'-5'OAS en cada grupo se comparó en términos de porcentaje de aumento con respecto a la incorporación basal de 3H-ATP. Los linfocitos de pacientes con infecciones virales tienen un 377,9ñ195,3% de aumento de actividad 2'-5'OAS; las infecciones bacterianas alcanzan a un 98,2ñ53,2%. El ensayo enzimático que se describe, ha resultado particularmente útil para diferenciar orígenes etiológicos en el síndrome febril prolongado