The role of interferon λ on antiviral immunity in upper respiratory tract / 上海预防医学

Upper respiratory tract is directly connected with the external environment， and its natural immune system is the first line of defense against pathogens. In antiviral infection， interferon （IFN） is the main component of the antiviral natural immune system and IFN-λ is a newly discovered immune effector molecule that is mainly produced in the mucosal barrier. IFN-λ exerts a biological role through Janus kinase （JAK） and signal transducer and activator of transcription （STAT） signaling pathway， and plays an important part in regulating innate and acquired immunity of respiratory mucosa. IFN-λ principally expresses on the mucosal barrier with a long-lasting antiviral impact and controls immune-inflammatory damage， which is becoming a new focus of antiviral immunity research in the upper respiratory tract， especially in fighting against 2019 novel coronavirus diseases （COVID-19）. Thus， we summarize the research progress of IFN-λ antiviral immunity in the upper respiratory tract to provide new insight in the prevention and treatment of viral infection in the upper respiratory tract.

Correlations between genetic polymorphism of IFN-λ family gene and HBV infection, virus replication and clearance / 生物工程学报

Hepatitis B virus (HBV) infection is one of the most serious public health problems. HBV infection could lead to hepatitis B, and even further develop into hepatic cirrhosis and hepatocellular carcinoma. Interferon lambda (IFN-λ) is a member of the interferon (IFN) family and an important cytokine for antiviral defense. There are four members in IFN-λ family, including IFN-λ1, IFN-λ2, IFN-λ3, and IFN-λ4. The genetic polymorphisms in the IFN-λ genes are associated with HBV replication and treatment response of HBV patients. In this review, we summarized the roles of genetic polymorphisms of the IFN-λ genes played in HBV infection, disease progression and treatment, with the aim to better understand their function. This review could serve as a reference for the HBV prevention and treatment of HBV patients, as well as for future clinical usage.

Nucleocapsid protein from porcine epidemic diarrhea virus isolates can antagonize interferon-λ production by blocking the nuclear factor-κB nuclear translocation / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Porcine epidemic diarrhea virus (PEDV) is a highly infectious pathogen that can cause severe diseases in pigs and result in enormous economic losses in the worldwide swine industry. Previous studies revealed that PEDV exhibits an obvious capacity for modulating interferon (IFN) signaling or expression. The newly discovered type III IFN, which plays a crucial role in antiviral immunity, has strong antiviral activity against PEDV proliferation in IPEC-J2 cells. In this study, we aimed to investigate the effect of PEDV nucleocapsid (N) protein on type III IFN-λ. We found that the N proteins of ten PEDV strains isolated between 2013 and 2017 from different local farms shared high nucleotide identities, while the N protein of the CV777 vaccine strain formed a monophyletic branch in the phylogenetic tree. The N protein of the epidemic strain could antagonize type III IFN, but not type I or type II IFN expression induced by polyinosinic-polycytidylic acid (poly(I:C)) in IPEC-J2 cells. Subsequently, we demonstrated that the inhibition of poly(I:C)-induced IFN-λ3 production by PEDV N protein was dependent on the blocking of nuclear factor-κB (NF-κB) nuclear translocation. These findings might help increase understanding of the pathogenesis of PEDV and its mechanisms for evading the host immune response.

Effect of interferon-λ1 on the function of peripheral blood mononuclear cell derived dendritic cells in adolescents with chronic hepatitis B virus infection / 中华传染病杂志

Objective To observe the effect of interferon (IFN) λ1 on the function of peripheral blood mononuclear cell (PBMC) derived dendritic cells (DC) in adolescents with chronic hepatitis B virus (HBV) infection.Methods A total of 34 adolescent patients with chronic HBV infection including 16 cases in immune clearance phase and 18 cases in immune tolerant phase,and 10 healthy youths were enrolled in the study.PBMC from all samples were isolated and then cultured according to the following 3 groups.IFN-λ1 group:cultured with IFN-λ1 only; normal group:cultured with recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) and recombinant human interleukin-4 (rhIL-4); combination group:cultured with IFN-λ1,rhGM-CSF and rhIL-4.The shape of DC was observed and the phenotypic patterns of CD83,CD80,CD86 and human leucocyte antigen (HLA)-DR were characterized by flow cytometry.The levels of interleukin 12 (IL-12) and IFN-γ in the supernatant produced by DC were analyzed with enzyme-linked immunosorbent assay (ELISA).Independent-samples t test was used to compare means between two groups and one-way ANOVA was used to compare means among multiple groups.Results In the IFN-λ1 group,the shape of adherent cells showed no change after 7 days of culture.In the normal group and combination group,typical morphology of mature state DC was observed.The expressions of phenotypic patterns of CD83,CD80,CD86 and HLA-DR in DC from immune tolerant phase patients were lower than those from healthy control youths and immune clearance phase patients (F=14.82-46.32,all P＜0.01).Co-stimuation of IFN-λ1 with rhGM-CSF and rhIL-4 up-regulated the expressions of phenotypic patterns on DC.Among patients both in immune tolerant phase and immune clearance phase,the expressions of CD83,CD80,CD86 and HLA-DR in the combination group were higher than those in normal group (t=3.16-5.69,all P＜0.01).In the normal group,the levels of IL-12 and IFN-γ in culture supernatants from healthy aldolescents were (287.25 ± 19.78) pg/mL and (56.38 ± 15.27)pg/mL,respectively; those from patients in immune tolerant phase were (198.42±22.28) pg/mL and (29.36±8.45) pg/mL,respectively; those from patients in immune clearance phase were (256.12±18.43) pg/mL and (38.38±9.72) pg/mL,respectively (F=69.22 for IL-12,F=20.29 for IFN-γ,both P＜0.01).IFN-λ1 combined with rhGM-CSF and rhIL-4 significantly up-regulated the secretion of IL-12 and IFN-γ by matured DC from patients both in immune tolerant phase and immune clearance phase (t=4.69-8.55,all P＜0.01).Conclusions In adolescent patients with chronic HBV infection,the DC function is markedly impaired in those in immune tolerant phase,compared with patients in immune clearance phase and healthy youths.IFN-λ1 can promote the maturation and phenotypic pattern expression of PBMC derived DC in adolescents with chronic HBV infection both in immune tolerant phase and immune clearance phase.