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The newly emerging coronavirus SARS-CoV-2 causes severe lung disease and substantial mortality. How the virus evades host defense for efficient replication is not fully understood. In this report, we found that the SARS-CoV-2 nucleocapsid protein (NP) impaired stress granule (SG) formation induced by viral RNA. SARS-CoV-2 NP associated with the protein kinase PKR after dsRNA stimulation. SARS-CoV-2 NP did not affect dsRNA-induced PKR oligomerization, but impaired dsRNA-induced PKR phosphorylation (a hallmark of its activation) as well as SG formation. SARS-CoV-2 NP also targeted the SG-nucleating protein G3BP1 and impaired G3BP1-mediated SG formation. Deficiency of PKR or G3BP1 impaired dsRNA-triggered SG formation and increased SARS-CoV-2 replication. The NP of SARS-CoV also targeted both PKR and G3BP1 to impair dsRNA-induced SG formation, whereas the NP of MERS-CoV targeted PKR, but not G3BP1 for the impairment. Our findings suggest that SARS-CoV-2 NP promotes viral replication by impairing formation of antiviral SGs, and reveal a conserved mechanism on evasion of host antiviral responses by highly pathogenic human betacoronaviruses.

A novel SARS-related coronavirus (SARS-CoV-2) has recently emerged as a serious pathogen that causes high morbidity and substantial mortality. However, the mechanisms by which SARS-CoV-2 evades host immunity remain poorly understood. Here, we identified SARS-CoV-2 membrane glycoprotein M as a negative regulator of the innate immune response. We found that the M protein interacted with the central adaptor protein MAVS in the innate immune response pathways. This interaction impaired MAVS aggregation and its recruitment of downstream TRAF3, TBK1, and IRF3, leading to attenuation of the innate antiviral response. Our findings reveal a mechanism by which SARS-CoV-2 evades the innate immune response and suggest that the M protein of SARS-CoV-2 is a potential target for the development of SARS-CoV-2 interventions.

We fabricated surface-enhanced Raman scattering (SERS) substrates using gold nanoparticle (AuNP)-decorated zinc oxide (ZnO) nanorods (NRs). Prior to decoration with AuNPs, ZnO NRs on the glass substrate fabricated using the sol&ndash, gel method could enhance the SERS signal for detecting 10&minus, 5 M rhodamine 6G (R6G). Microscopic analysis revealed that the thermal-annealing process for fabricating the seed layers of ZnO facilitated the growth of ZnO NRs with the highly preferred c-axis (002) orientation. A decrease in the diameter of ZnO NRs occurred because of the use of annealed seek layers further increased the surface-to-volume ratio of ZnO NRs, resulting in an increase in the SERS signal for R6G of 10&minus, 5 M. To combine the localized surface plasmon resonance (LSPR) mode with the charge transfer (CT) mode, ZnO NRs were decorated with AuNPs through pulsed-laser-induced photolysis (PLIP). However, the preferred vertical (002) orientation of ZnO NRs was prone to the aggregation of AuNPs, which hindered the SERS signal. The experimental results revealed that ZnO NRs with the crystalline structure of horizontal (100) and (101) orientations facilitated the growth of homogeneous, independent and isolated AuNPs which serves as &ldquo, hot spots&rdquo, for SERS signal of detecting R6G at a low concentration of 10&minus, 9 M. Comparing to previous fabrication of SERS substrate, our method has advantage to fabricate AuNP-decorated ZnO NR in a short time. Moreover, the optimization of the SERS behaviors for different fabrication conditions of AuNPs using the PLIP method was investigated in detail.

Cyclic GMP-AMP synthase (cGAS) senses double-stranded DNA and synthesizes the second messenger cyclic GMP-AMP (cGAMP), which binds to mediator of IRF3 activation (MITA) and initiates MITA-mediated signaling, leading to induction of type I interferons (IFNs) and other antiviral effectors. Human cytomegalovirus (HCMV), a widespread and opportunistic pathogen, antagonizes the host antiviral immune response to establish latent infection. Here, we identified HCMV tegument protein UL94 as an inhibitor of the cGAS-MITA-mediated antiviral response. Ectopic expression of UL94 impaired cytosolic double-stranded DNA (dsDNA)- and DNA virus-triggered induction of type I IFNs and enhanced viral replication. Conversely, UL94 deficiency potentiated HCMV-induced transcription of type I IFNs and downstream antiviral effectors and impaired viral replication. UL94 interacted with MITA, disrupted the dimerization and translocation of MITA, and impaired the recruitment of TBK1 to the MITA signalsome. These results suggest that UL94 plays an important role in the immune evasion of HCMV. IMPORTANCE Human cytomegalovirus (HCMV), a large double-stranded DNA (dsDNA) virus, encodes more than 200 viral proteins. HCMV infection causes irreversible abnormalities of the central nervous system in newborns and severe syndromes in organ transplantation patients or AIDS patients. It has been demonstrated that HCMV has evolved multiple immune evasion strategies to establish latent infection. Previous studies pay more attention to the mechanism by which HCMV evades immune response in the early phase of infection. In this study, we identified UL94 as a negative regulator of the innate immune response, which functions in the late phase of HCMV infection.

Recognition of human cytomegalovirus (HCMV) DNA by the cytosolic sensor cGAS initiates STING-dependent innate antiviral responses. HCMV can antagonize host immune responses to promote latency infection. However, it is unknown whether and how HCMV targets the cGAS-STING axis for immune evasion. Here we identified the HCMV tegument protein UL82 as a negative regulator of STING-dependent antiviral responses. UL82 interacted with STING and impaired STING-mediated signaling via two mechanisms. UL82 inhibited the translocation of STING from the ER to perinuclear microsomes by disrupting the STING-iRhom2-TRAPβ translocation complex. UL82 also impaired the recruitment of TBK1 and IRF3 to the STING complex. The levels of downstream antiviral genes induced by UL82-deficient HCMV were higher than those induced by wild-type HCMV. Conversely, wild-type HCMV replicated more efficiently than the UL82-deficient mutant. These findings reveal an important mechanism of immune evasion by HCMV.

Innate immunity is the first line of host defense against viral invasion. The induction of type I interferons (IFNs) and inflammatory cytokines is essential to host antiviral immune responses, which are also key targets of viral immune evasion. Human cytomegalovirus (HCMV) can establish long-term latent infections, in which immune evasion is a pivotal step. In this study, we identified HCMV protein UL44, a DNA polymerase processivity factor, as an inhibitor of the interferon regulatory factor 3 (IRF3)- and NF-κB-dependent antiviral response. Ectopic expression of UL44 inhibited HCMV-triggered induction of downstream effector genes and enhanced viral replication. Conversely, knockdown of UL44 potentiated HCMV-triggered induction of downstream antiviral genes. UL44 interacted with IRF3 and p65, and it inhibited the binding of IRF3 and NF-κB to the promoters of their downstream antiviral genes. These findings reveal an important mechanism of immune evasion by HCMV at the transcriptional level. IMPORTANCE Induction of type I IFNs and inflammatory cytokines plays pivotal roles in host antiviral innate immune responses. Viruses have evolved various mechanisms to interfere with these processes. HCMV causes severe ailments in immunodeficient populations and is a major cause of birth defects. It has been shown that HCMV antagonizes host innate immune defenses, which is important for establishing immune evasion and latent infection. In this study, we identified the HCMV DNA polymerase subunit UL44 as a suppressor of antiviral innate immune responses. Overexpression of UL44 impaired HCMV-triggered induction of type I IFNs and other antiviral genes and thus potentiated viral replication, whereas UL44 deficiency showed opposite effects. Mechanistic studies indicated that UL44 acts by inhibiting the binding of IRF3 and NF-κB to the promoters of downstream antiviral genes. These findings defined an important mechanism of HCMV immune evasion at the transcriptional level, which may provide a therapeutic target for the treatment of HCMV infection.

Cyclic GMP-AMP synthase (cGAS) senses viral DNA in the cytosol and then catalyzes synthesis of the second messenger cGAMP, which activates the ER-localized adaptor protein Mediator of IRF3 Activator (MITA) to initiate innate antiviral response. Human cytomegalovirus (HCMV) proteins can antagonize host immune responses to promote latent infection. Here, we identified HCMV UL42 as a negative regulator of cGAS/MITA-dependent antiviral response. UL42-deficiency enhances HCMV-induced production of type I interferons (IFNs) and downstream antiviral genes. Consistently, wild-type HCMV replicates more efficiently than UL42-deficient HCMV. UL42 interacts with both cGAS and MITA. UL42 inhibits DNA binding, oligomerization and enzymatic activity of cGAS. UL42 also impairs translocation of MITA from the ER to perinuclear punctate structures, which is required for MITA activation, by facilitating p62/LC3B-mediated degradation of translocon-associated protein β (TRAPβ). These results suggest that UL42 can antagonize innate immune response to HCMV by targeting the core components of viral DNA-triggered signaling pathways., Author summary Recognition of viral DNA by the cytosolic DNA sensor cGAS and subsequent induction of type I IFNs via the cGAS-MITA signaling axis are important for host antiviral innate immunity. The human cytomegalovirus (HCMV) causes complications in immunodeficient populations and is a major cause of birth defects. It is known that HCMV suppresses innate immunity, which is pivotal for establishing immune evasion and latent infection. In this study, we found that HCMV protein UL42 inhibits innate antiviral responses thus promotes HCMV replication. UL42 functions by targeting cGAS and MITA through distinct mechanisms. UL42 inhibits cGAS activation by interrupting its DNA binding and oligomerization, while it targets MITA by interfering trafficking of MITA from the ER to perinuclear punctate structures, a process required for MITA activation. These findings defined an important mechanism for HCMV immune evasion, which may provide a therapeutic target for the treatment of HCMV infection.

According to the problem of emitter characteristic parameters are showed by interval and uneasy to identify, an emitter fusion recognition method based on the PSO-BP neural network is proposed. The method train the network by training samples which are reasonable structured according to the distribution in the interval, so as to determine the network structure and confirm the emitter type through the emitter characteristics parameters. At the same time, the BP neural network is optimized by Particle Swarm Optimization (PSO) algorithm. The coding method of the network output, training data size and deviation rate on the influence of the recognition are researched by simulation, and the validity of this method are verified by the results.

Summary The cytosolic DNA sensor cGAS recognizes viral DNA and synthesizes the second messenger cGAMP upon viral infection. cGAMP binds to the adaptor protein MITA/STING to activate downstream signaling events, leading to induction of type I interferons (IFNs) and antiviral effector genes. Here we identify the human cytomegalovirus (HCMV) protein UL31 as an inhibitor of cGAS. UL31 interacts directly with cGAS and disassociates DNA from cGAS, thus inhibiting cGAS enzymatic functions and reducing cGAMP production. UL31 overexpression markedly reduces antiviral responses stimulated by cytosolic DNA, while knockdown or knockout of UL31 heightens HCMV-triggered induction of type I IFNs and downstream antiviral genes. Moreover, wild-type HCMV replicates more efficiently than UL31-deficient HCMV, a phenotype that is reversed in cGAS null cells. These results highlight the importance of cGAS in the host response to HCMV as well as an important viral strategy to evade this innate immune sensor.

Aiming at the shortcomings of traditional radar identification based on artificial judgment and module matching, this paper proposes an intelligent identification algorithm based on joint time-frequency. The radar radiation source signal is transformed by time-frequency, and the processed signal is input into the automatic encoder through different kinds of dimensionality reduction methods, and the pre-training adjustment depth learning model is adopted, and the commonly used softmax classifier is adopted to the pre-training model. Oversee fine school and identification, and finally complete the identification task. The simulation results show that high recognition rate can be achieved by this algorithm, and the joint dimension reduction is better than other methods.

Circulating microRNAs (miRNAs) were recognized to be potential non-invasive biomarkers for colorectal cancer (CRC) detection and prediction. Meanwhile, the association of the expression of plasma miRNAs with the risk of CRC patients has rarely been analyzed. Therefore, we conducted this study to evaluate the value of plasma miRNAs for CRC diagnosis and risk estimation. Fasting blood samples from 100 CRC patients and 79 cancer-free controls were collected. Plasma miR-106a, miR-20a, miR-27b, miR-92a and miR-29a levels were detected by RT-qPCR. Sensitivity and specificity were employed to evaluate the diagnostic value of miRNAs for CRC. Univariate and multivariate logistic regression were employed to analyze the association between miRNAs expression and CRC risk. As results, miR-106a and miR-20a were elevated in the patients with CRC. The sensitivity of miR-106a was 74.00% and the specificity was 44.40%, while the cutoff value was 2.03. As for miR-20a, the sensitivity was 46.00% and specificity was 73.42% when employed 2.44 as cutoff value. High expression of plasma miR-106a increased CRC risk by 1.80 -fold. Plasma miR-106a and miR-20a may as noninvasive biomarkers for detecting the CRC. High expression of miR-106a associated with CRC risk.