Effect and Mechanism of Menispermi Rhizoma Total Alkaloids on Antiviral Infection / 中国实验方剂学杂志

ObjectiveTo investigate the antiviral effect of Menispermi Rhizoma total alkaloids and its relationship with the type Ⅰ interferon （IFN-Ⅰ） signaling pathway. MethodThe effects of Menispermi Rhizoma total alkaloids on the intracellular replication of influenza A virus （H1N1）， vesicular stomatitis virus （VSV）， and cerebral myocarditis virus （EMCV） were detected by fluorescent inverted microscope， flow cytometry， Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and Western blot. A mouse model infected with H1N1 was constructed， and the mice were divided into a control group， H1N1 model group， Menispermi Rhizoma total alkaloids groups （10， 20， 30 mg·kg-1）， and oseltamivir group （40 mg·kg-1）， so as to study the effects on the weight and survival rate of infected mice. Real-time PCR was used to detect the activation effect of Menispermi Rhizoma total alkaloids on the IFN-Ⅰ pathway in cells， and the relationship between the antiviral effect of Menispermi Rhizoma total alkaloids in IFNAR1 knockout A549 cells （IFNAR1-/--A549） and IFN-Ⅰ pathway was detected. ResultCompared with the control group， the virus proliferated significantly in the model group （P<0.01）. Compared with the model group， Menispermi Rhizoma total alkaloids could significantly inhibit the replication of H1N1， VSV， and EMCV in vitro （P<0.01）， inhibit the weight loss of the mice infected with the H1N1 in vivo， and improve the survival rate of mice （P<0.05）. In addition， Menispermi Rhizoma total alkaloids activated the IFN-I pathway and relied on this pathway to exert the function of antiviral infection. ConclusionMenispermi Rhizoma total alkaloids exert antiviral effects in vivo and in vitro by activating the IFN-Ⅰ pathway.

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.

Sex differences in SARS-CoV-2 infections, anti-viral immunity and vaccine responses

The COVID-19 pandemic has revealed sex-based differences in anti-viral responses, with a higher rate of SARS-CoV-2 infections as well as a higher rate of morbidity and mortality in men than in women. Males and females also show disparate immune responses to COVID-19 infection, which may be important contributors to lower rates of infection, disease severity and deaths in women than in men. Here, the authors review sex differences in SARSCoV- 2 infections, anti-viral immunity and vaccine responses, putting forth the importance of sex, the underappreciated variables in vaccine response and disease infectivity.

TRIM35 mediates protection against influenza infection by activating TRAF3 and degrading viral PB2

Tripartite motif (TRIM) family proteins are important effectors of innate immunity against viral infections. Here we identified TRIM35 as a regulator of TRAF3 activation. Deficiency in or inhibition of TRIM35 suppressed the production of type I interferon (IFN) in response to viral infection. Trim35-deficient mice were more susceptible to influenza A virus (IAV) infection than were wild-type mice. TRIM35 promoted the RIG-I-mediated signaling by catalyzing Lys63-linked polyubiquitination of TRAF3 and the subsequent formation of a signaling complex with VISA and TBK1. IAV PB2 polymerase countered the innate antiviral immune response by impeding the Lys63-linked polyubiquitination and activation of TRAF3. TRIM35 mediated Lys48-linked polyubiquitination and proteasomal degradation of IAV PB2, thereby antagonizing its suppression of TRAF3 activation. Our in vitro and in vivo findings thus reveal novel roles of TRIM35, through catalyzing Lys63- or Lys48-linked polyubiquitination, in RIG-I antiviral immunity and mechanism of defense against IAV infection.

The Function and Regulatory Mechanism of TBK1 in Antiviral Innate Immunity / 中山大学学报(医学科学版)

@#TANK- binding kinase 1（TBK1）acts as the hub of antiviral innate immune signal transduction. On the one hand，TBK1 could be activated by a variety of pattern recognition receptors（PRR）. On the other hand，as a critical kinase，activated TBK1 phosphorylates varieties of substrates，such as transcription factors interferon regulatory factor 3（IRF3）and IRF7 ，resulting in the initiation of antiviral innate immune responses. In this review ，we put emphasis on the TBK1 associated antiviral innate immune signaling ，as well as the regulation mechanisms of TBK1 expression and activation.