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Objective:To investigate the role and regulatory mechanism of miR-125b-1-3p in rotavirus replication.Methods:MA104 cells were infected with rotavirus after upregulation and down-regulation of miR-125b-1-3p, respectively. The expression of miR-125b-1-3p and the copy number of rotavirus were analyzed by RT-PCR. The effect of miR-125b-1-3p on the protein expression of rotavirus was analyzed by immunofluorescence. The expression of related proteins involved in the regulation of miR-125b-1-3p was analyzed by Western blot analysis.Results:After rotavirus infection, the expression level of miR-125b-1-3p was significantly up-regulated, the copy number of VP7 and NSP3 gene of rotavirus decreased after up-regulation of miR-125b-1-3p, and the copy number of VP7 and NSP3 gene of rotavirus was significantly increased after down-regulation of miR-125b-1-3p.The fluorescence number of rotavirus protein decreased after upregulation of miR-125b-1-3p expression level, and increased after down-regulation of miR-125b-1-3p expression level. The activity of PI3K/Akt pathway was inhibited 16 h after rotavirus infection, and the up-regulation of miR-125b-1-3p could inhibit the activation of PI3K/Akt pathway.Conclusions:MiR-125b-1-3p inhibits rotavirus replication by regulating the PI3K/Akt pathway. These results provide an experimental basis for exploring the specific regulatory mechanism between miR-125b-1-3p and PI3K/Akt pathway, and provide a target for anti-infection therapy of rotavirus.
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Toll-like receptor 3 (TLR3) is a member of the TLR family, mediating the transcriptional induction of type I interferons (IFNs), proinflammatory cytokines, and chemokines, thereby collectively establishing an antiviral host response. Studies have shown that unlike other TLR family members, TLR3 is the only RNA sensor that is utterly dependent on the Toll-interleukin-1 receptor (TIR)-domain-containing adaptor-inducing IFN-β (TRIF). However, the details of how the TLR3-TRIF signaling pathway works in an antiviral response and how it is regulated are unclear. In this review, we focus on recent advances in understanding the antiviral mechanism of the TRIF pathway and describe the essential characteristics of TLR3 and its antiviral effects. Advancing our understanding of TLR3 may contribute to disease diagnosis and could foster the development of novel treatments for viral diseases.
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Nuclear bodies are membrane-free nuclear substructures that are localized in the mammalian nuclear matrix region. They are multiprotein complexes that recruit other proteins to participate in various cellular activities, such as transcription, RNA splicing, epigenetic regulation, tumorigenesis and antiviral defense. It is of great significance to clarify the functions and regulatory mechanisms of nuclear bodies to probe related diseases and virus-host interactions. This review takes several nuclear bodies associated proteins as examples, summarizes the formation process, structure and functions of nuclear bodies, and focuses on their important roles in antiviral infection. It is expected to provide new insight into host antiviral mechanisms.
Subject(s)
Animals , Cell Nucleus , Epigenesis, Genetic , Intranuclear Inclusion Bodies/metabolism , Nuclear Proteins/metabolismABSTRACT
BACKGROUND Dengue viruses (DENV) are considered one of the most important emerging pathogens and dengue disease is a global health threat. The geographic expansion of dengue viruses has led to co-circulation of all four dengue serotypes making it imperative that new DENV control strategies be devised. OBJECTIVES Here we characterize dengue serotype-specific innate immune responses in Aedes aegypti and Aedes albopictus using DENV from Puerto Rico (PR). METHODS Ae. aegypti and Ae. albopictus were infected with dengue serotype 1 and 2 isolated from Puerto Rico. DENV infected mosquito samples were collected and temporal change in expression of selected innate immune response pathway genes analyzed by quantitative real time PCR. FINDINGS The Toll pathway is involved in anti-dengue response in Ae. aegypti, and Ae. albopictus. Infections with PR DENV- 1 elicited a stronger response from genes of the Toll immune pathway than PR DENV-2 in Ae. aegypti but in infected Ae. albopictus expression of Toll pathway genes tended to be similar between the serotypes. Two genes (a ribosomal S5 protein gene and a nimrod-like gene) from Ae. albopictus were expressed in response to DENV. MAIN CONCLUSIONS These studies revealed a role for antiviral genes in DENV serotype-specific interactions with DENV vectors, demonstrated that infections with DENV-2 can modulate the Toll immune response pathway in Ae. aegypti and elucidated candidate molecules that might be used to interfere with serotype specific vector-virus interactions.
Subject(s)
Animals , Aedes/classification , Aedes/virology , Dengue Virus/isolation & purification , Dengue Virus/genetics , Dengue Virus/immunology , Insect Vectors/classification , Insect Vectors/virology , Real-Time Polymerase Chain ReactionABSTRACT
Objective To investigate the relationship between interleukin (IL)-28B gene polymorphisms (rs12979860 and rs8099917) and treatment response in patients with chronic hepatitis C in China.Methods Taqman probes single nucleotide polymorphism genotyping methods were used to detect the genotypes of rs12979860 (C/T) and rs8099917 (T/G) located at IL-28B gene in 105 included patients.The patients were treated with standard doses of pegylated interferon plus ribavirin and were followed up regularly for therapeutic response and adverse reaction.The relationship between IL-28B gene polymorphism and antiviral treatment response of patients were analyzed.Categorical data were analyzed using Pearson chi-square test or Fisher exact test.Results Totally 105 cases were included in our study and 2 cases lost to follow-up because of moving away.Eight-one cases (78.6%) of the remaining 103 patients were CC/TT genotype (CC/TT group) at rs12979860 and rs8099917, 19 cases (18.4%) were CT/TG (CT/TG group) and 3 cases (2.9%)were TT/TG (TT/TG group).No other genotypes were detected and linkage disequilibrium was discovered at the two polymorphism loci (r2=0.11).After 4 weeks of treatment, 35 cases (43.2%) in CC/TT group, 3 cases (15.8%) in CT/TG group and non in TT/TG group achieved rapid virological response (RVR).There were statistically significant differences among three groups (P=0.033).After 12 weeks of treatment, 45 cases (55.6%) in CC/TT group, 6 cases (31.6%) in CT/TG group and none in TT/TG group achieved early virological response (EVR).There were statistically significant differences among three groups (P=0.025).At the end of the treatment, 68 cases (83.9%) in CC/TT group, 10 cases (52.6%) in CT/TG group and only 1 case (33.3%) in TT/TG group achieved end-of-treatment response (ETR).There were significant statistical differences among the three groups (P=0.003).After 24 weeks of follow-up, 62 cases (76.5%) in CC/TT group, 9 cases (47.4%) in CT/TG group and 1 case (33.3%) in TT/TG group achieved sustained virological response (SVR).There were statistically significant differences among the three groups (P=0.014).One hundred and one cases in CC/TT group developed adverse events, among them 19 cases needed clinical treatment.There were 43 cases in CT/TG group developed adverse events and 9 cases needed treatment.Seven cases in TT/TG group developed adverse events and only 1 case needed treatment.There were no statistically significant difference among three groups (χ2=0.139,P>0.05).Conclusions The genotype of rs12979860 (C/T) and rs8099917 (T/G) at IL-28B gene could affect the treatment response in patients with chronic hepatitis C.RVR and SVR are higher in patients with genotype CC/TT, which might help to guide HCV treatment.