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1.
Ital J Pediatr ; 46(1): 88, 2020 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-32600431

RESUMO

BACKGROUND: Cerebral palsy (CP) is a non-progressive disorder of movement and posture due to a static insult to the brain. In CP, the depth of investigation is guided by the patients' medical history and their clinical examination. Magnetic resonance imaging (MRI) has a high yield and is widely used for investigation in CP. CASE PRESENTATION: In this paper, we report a novel DDX3X variant in a girl afflicted with the X-linked mental retardation-102 (MRX102). The girl had been misdiagnosed with CP in her early life based on a comprehensive clinical evaluation and associated clinical features, such as developmental delay, reduced activities of the arms and legs, and abnormal brain MRI. Subsequently, whole-exome sequencing was applied to better distinguish between CP and actual MRX102 with similar characteristics. CONCLUSIONS: We report on a de novo heterozygous DDX3X variant mimicking cerebral palsy and suggest a thorough and conscientious review during diagnosis of CP.

2.
Reprod Health ; 17(1): 93, 2020 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-32527333

RESUMO

BACKGROUND: It has been reported that lifestyle factors may affect birth weight; however, few studies have explored the association between lifestyle factors and low birth weight in preterm and term births in China. The objective of this study was to explore the effect of lifestyle on low birth weight in preterm and term births. METHODS: This case-control study was conducted in fourteen hospitals in Jiangmen, Guangdong Province. Data were collected from August 2015 to May 2016 using a standard questionnaire. Data were analysed using logistic regression. RESULTS: Women who delivered preterm and were physically active (1-3 times per week and ≥ 4 times per week) had reduced odds of having low birth weight babies (aOR = 0.584, 95%CI = 0.394-0.867 and, aOR = 0.516, 95%CI = 0.355-0.752, respectively). Pregnant women who had insufficient gestational weight gain had increased odds of having low birth weight babies (aOR = 2.272, 95%CI = 1.626-3.176). Women exposed to passive smoking had an increased risk of delivering low birth weight infants (aOR = 1.404, 95%CI = 1.057-1.864). Insufficient gestational weight gain and excessive gestational weight gain were both significantly associated with low birth weight (aOR = 1.484, 95%CI = 1.103-1.998 and aOR = 0.369, 95%CI = 0.236-0.577, respectively) for term deliveries. In addition, parity, history of low birth weight, antenatal care and gestational hypertension were significantly associated with the likelihood of low birth weight. CONCLUSION: Pregnant women without exercise contraindications should remain physically active. Pregnant women should be aware of the negative effects of smoke and be aware of strategies to protect themselves from passive smoke exposure. Hospitals should inform pregnant women of the importance appropriate gestational weight gain. These recommendations should be put into practice to decrease the prevalence of low birth weight infants.

3.
Psychiatry Res ; 291: 113190, 2020 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-32563745

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic has caused enormous psychological impact worldwide. We conducted a systematic review and meta-analysis on the psychological and mental impact of COVID-19 among healthcare workers, the general population, and patients with higher COVID-19 risk published between 1 Nov 2019 to 25 May 2020. We conducted literature research using Embase, PubMed, Google scholar and WHO COVID-19 databases. Among the initial search of 9207 studies, 62 studies with 162,639 participants from 17 countries were included in the review. The pooled prevalence of anxiety and depression was 33% (95% confidence interval: 28%-38%) and 28% (23%-32%), respectively. The prevalence of anxiety and depression was the highest among patients with pre-existing conditions and COVID-19 infection (56% [39%-73%] and 55% [48%-62%]), and it was similar between healthcare workers and the general public. Studies from China, Italy, Turkey, Spain and Iran reported higher-than-pooled prevalence among healthcare workers and the general public. Common risk factors included being women, being nurses, having lower socioeconomic status, having high risks of contracting COVID-19, and social isolation. Protective factors included having sufficient medical resources, up-to-date and accurate information, and taking precautionary measures. In conclusion, psychological interventions targeting high-risk populations with heavy psychological distress are in urgent need.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32537781

RESUMO

The first fluorosulfonic ultraviolet (UV) nonlinear optical (NLO) material, C(NH 2 ) 3 SO 3 F, is rationally designed by taking the KBe 2 BO 3 F 2 (KBBF) as the parent compound. C(NH 2 ) 3 SO 3 F features the similar topological layer with KBBF by replacing (BO 3 ) 3- with C(NH 2 ) 3 + triangles and the substitution of BeO 3 F with SO 3 F - tetrahedral. Therefore, C(NH 2 ) 3 SO 3 F is a metal-free UV NLO crystal. Benefiting from the coplanar configuration of the C(NH 2 ) 3 + cationic groups, it possesses large SHG response of 5×KDP and moderate birefringence of 0.133@1064 nm. Besides, it has a short UV cutoff edge of 200 nm. The calculated results reveal the shortest SHG phase - matching wavelength can reach 200 nm. These findings point out exploring metal-free compounds as nontoxic and lowcost UV NLO materials will be a new research area.

5.
Inorg Chem ; 2020 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-32597191

RESUMO

The first alkali-metal nitrate isocyanurates, A(H3C3N3O3)(NO3) (A = K, Rb), were synthesized by the tactic of introducing (NO3)- into isocyanurate with a mild hydrothermal technique. They crystallized into the same monoclinic centrosymmetric (CS) space group P21/c, which featured a 2D [(H3C3N3O3)(NO3)]∞ layered structure separated by K+ and Rb+ cations, respectively. Both compounds exhibited short ultraviolet cutoff edges (λcutoff = 228 and 229 nm) and large birefringences (Δn = 0.253 and 0.224 at 546.1 nm). More importantly, in comparison with most of the isocyanurates and nitrates, they have better thermal stability with decomposition temperatures up to 319.8 and 324.4 °C. In addition, our theoretical calculations reveal that the π-conjugated groups play significant roles in improving the optical anisotropy. Remarkably, introducing a π-conjugated inorganic acid radical (NO3)- into isocyanurate is an extremely meaningful strategy to explore new UV birefringent crystals.

6.
ACS Chem Neurosci ; 2020 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-32584547

RESUMO

Glioblastoma multiforme (GBM) is the most malignant form of glioma and the overall survival time of patients with GBM is usually less than 14 months. Therefore, it is urgent to find new and effective medicine for GBM. Recently, marine natural products have been shown to exhibit strong inhibitory effects on cancer cells, providing new avenue for exploring novel drugs for GBM treatment. In this study, we investigated the inhibitory effect of the Grincamycin (GCN) B-F, newly isolated from marine-derived Streptomyces Lusitanus SCSIO LR32, on GBM cells, and evaluated the mechanism of GCN B on GBM. The results, for the first time, showed that GCN B acted as a potent inhibitor to suppress growth and invasion of two human GBM cell lines U251 and 091214 in vitro. In addition, GCN B could effectively target GSCs in GBM evidenced by attenuated formation of tumor spheres and decrease of several markers of GSCs. Furthermore, we performed gene expression microarray followed by Signal-Net analysis. The result revealed that RhoA and PI3K/AKT axis played critical roles for GCN B-mediated inhibitory effect on GSCs. Altogether, our findings highlighted GCN B as a promising inhibitor for GSCs via targeting RhoA and PI3K/AKT.

7.
Acta Pharmacol Sin ; 41(7): 902-910, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32398683

RESUMO

Cancer immunotherapy is rapidly changing the paradigm of cancer care and treatment by evoking host immunity to kill cancer cells. As clinical approval of checkpoint inhibitors (e.g., ipilimumab and pembrolizumab) has been accelerated by a dramatic improvement of long-term survival in a small subset of patients compared to conventional chemotherapy, growing interesting research has focused on immunotherapy. However, majority of patients have not benefited from checkpoint therapies that only partially remove the inhibition of T cell functions. Insufficient systemic T cell responses, low immunogenicity and the immunosuppressive environment of tumors, create great challenges on therapeutic efficiency. Nanotechnology can integrate multiple functions within controlled size and shape, and has been explored as a unique avenue for the development of cancer immunotherapy. In this review, we mainly address how nanoengineered vaccines can induce robust T cell responses against tumors, as well as how nanomedicine can remodel the tumor immunosuppressive microenvironment to boost antitumor immune responses.

8.
Cell Mol Immunol ; 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32398808

RESUMO

Exposure to ionizing radiation, a physical treatment that inactivates live tumor cells, has been extensively applied to enhance the antitumor responses induced by cancer cell vaccines in both animal research and human clinical trials. However, the mechanisms by which irradiated cells function as immunogenic tumor vaccines and induce effective antitumor responses have not been fully explored. Here, we demonstrate that oxidized mitochondrial DNA (mtDNA) and stimulator of interferon genes (STING) signaling play a key roles in the enhanced antitumor effect achieved with an irradiated tumor cell vaccine. Elevations in ROS and oxidized mtDNA 8-OHG content could be induced in irradiated tumor cells. Oxidized mtDNA derived from irradiated tumor cells gained access to the cytosol of dendritic cells (DCs). Oxidized mtDNA, as a DAMP or adjuvant, activated the STING-TBK1-IRF3-IFN-ß pathway in DCs, which subsequently cross-presented irradiated tumor cell-derived antigens to CD8+ T cells and elicited antitumor immunity. The results of our study provide insight into the mechanism by which an irradiated cell vaccine mediates antitumor immunity, which may have implications for new strategies to improve the efficacy of irradiated vaccines.

9.
Inorg Chem ; 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32401026

RESUMO

Two novel zinc borate halides named Zn2BO3X·H2O (X = Cl, Br) were discovered through hydrothermal techniques. Both compounds are isomorphic and feature the layered structure similar to that of KBBF, consisting of the infinite planar [Zn2BO3X·OH2] (X = Cl, Br) layers. Compared with the weak ionic bond between adjacent layers in KBBF, the strong interaction of hydrogen bonds between layers in Zn2BO3X·H2O (X = Cl, Br) effectively enhances the interlayer force, contributing to eliminating the layering growth tendency. Optical measurements on these two NLO crystals revealed that they have a broad wavelength transparency window and a moderate NLO coefficient. Moreover, the theoretical calculations revealed that the linear and NLO properties primarily depended on the [BO3] and [ZnO3Cl/Br] groups in both crystals.

10.
BMC Gastroenterol ; 20(1): 136, 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32375670

RESUMO

BACKGROUND: Tumor-to-tumor metastasis is a rare event. Rectal cancer to primary thyroid neoplasm metastasis is extremely rare. Herein, we reported a case of metastatic rectal adenocarcinoma to a papillary thyroid carcinoma. The incidence and clinicopathological characteristics of metastatic colorectal cancer to a thyroid gland neoplasm were described, and the pertinent literature was reviewed. CASE PRESENTATION: A 34-year-old female patient had curative treatment of initial rectal adenocarcinoma in 2012, and was found to have lung metastases by follow-up CT scan 3 years later. In 2018, she was found to have thyroid metastasis by imaging due to left neck pain and hoarseness. A fine-needle aspiration biopsy (FNAB) result suggested suspicious papillary thyroid carcinoma (PTC). The patient underwent a total thyroidectomy and bilateral cervical lymph nodes dissection. The histopathology of thyroidectomy specimen revealed a rectal adenocarcinoma metastatic to the thyroid concomitant with the papillary carcinoma in metastatic adenocarcinoma. The patient received levothyroxine supplementation therapy and palliative chemotherapy with irinotecan and anti-angiogenesis for the metastatic rectal adenocarcinoma. After 1 year of thyroidectomy, no newly developed lesion evidence of recurrent PTC was observed. The patient remains still alive. CONCLUSION: The possibility of metastases should be considered in patients with a history of rectal cancer and with a thyroid lesion, particularly in those with ageing, hereditary nonpolyposis colorectal cancer (HNPCC) or long-term survival. The diagnosis should be histologically confirmed for the presence of both primary thyroid lesions and secondary thyroid neoplasms. Thyroidectomy may be a feasible treatment for symptomatic thyroid metastasis or thyroid cancer. we need to gain more available evidence from large or multi-center clinical data to help clinicians to diagnose rectal cancer to thyroid neoplasm metastases and evaluate treatment.

11.
Br J Pharmacol ; 2020 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-32472692

RESUMO

BACKGROUND AND PURPOSE: There is an urgent but unmet need for mitigating radiation-induced intestinal toxicity while radio sensitising tumours for abdominal radiotherapy. We aimed to investigate the effects of metformin on radiation-induced intestinal toxicity and radiosensitivity of colorectal tumours. EXPERIMENTAL APPROACH: Acute and chronic histological injuries of the intestine from mice were used to assess radioprotection, and IEC-6 cell line was used to investigate the mechanisms in vitro. The fractionated abdominal radiation model of HCT116 and HT29 tumour grafts was used to determine the effects on colorectal cancer. KEY RESULTS: Metformin alleviated radiation-induced acute and chronic intestinal toxicity by optimising mitophagy which was AMPK-dependent. In addition, our data indicated that metformin increased the radiosensitivity of colorectal tumours with P53 mutation both in vitro and in vivo. CONCLUSION AND IMPLICATIONS: Metformin may be a radiotherapy adjuvant agent for colorectal cancers especially those carrying P53 mutation. Our findings provide a new strategy for further precise clinical trials for metformin on radiotherapy.

12.
Int J Biol Macromol ; 158: 265-274, 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32380099

RESUMO

Searching for a sustainable precursor that is capable of absorbing microwave energy is crucial for its rapid conversion into porous carbon via microwave heating. Here, alginate-based hydrogel beads cross-linked by bivalent ions (Cu2+, Zn2+, and Ca2+) are converted into porous carbons (SPCs) in 10 min by applying simple microwave-assisted pyrolysis. Water wrapped in hydrogel beads and bivalent ions serve as initial microwave absorbers to convert alginate into char which acts as a good microwave absorber in the following stages. Additionally, bivalent ions also act as a gelling agent to generate hydrogel beads, as a porogen to obtain a highly porous structure, and as a metal donor to form the SPC/Cu composite. The resultant SPC has a high specific surface area of 1336 m2 g-1, a large total pore volume of 0.56 cm3 g-1, interconnected macropores, as well as a high oxygen content of up to 13.2%. These attractive characteristics give SPC a remarkable rate capability of 72% at 50 A g-1. Interestingly, the interconnected macropores in SPC offer sufficient space for Cu growth via the redox reactions of Cu2+; thus, the SPC/Cu composite without acid wash shows a specific capacitance as high as 804 F g-1 at 0.5 A g-1.

13.
Rev Sci Instrum ; 91(4): 044705, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32357687

RESUMO

A repetitive electron beam driver based on 6-stage Linear Transformer Driver (LTD) cavities is presented. Each cavity consists of two Blumlein pulse forming networks (BPFNs) sharing a laser trigger switch. Voltage adding is obtained by means of Linear Transformer (LT) technology. The LTD cavity consists of two BPFNs connected in parallel, an LT with a ratio of 1:1, and a laser-triggered spark switch. The energy efficiency of a single LTD was investigated. The results show that the energy efficiency of an L-type BPFN and an LT was 94.3% and 92.8%, respectively. An electron beam driver consisting of 6 such cavities was developed with an output voltage of 740 kV, a current of 12.3 kA, and a power of 9.1 GW. The repetition frequency operation results show that the electron beam driver can operate stably for 20 s at 25 Hz with a jitter of approximately 1.7 ns.

14.
Zhongguo Zhen Jiu ; 40(5): 513-8, 2020 May 12.
Artigo em Chinês | MEDLINE | ID: mdl-32394659

RESUMO

OBJECTIVE: To observe the effect of electroacupuncture (EA) on the expression of insulin phosphatidylinositol-3 kinase/glycogen synthetase kinase-3α (PI3K/GSK3α) signal pathway related proteins in the hippocampus in mice with Alzheimer's disease (AD), and to explore the regulatory mechanism of EA on improving the pathological characteristics of AD. METHODS: Twelve male APP/PS1 double transgenic mice were randomly divided a model group and a treatment group, 6 mice in each group; another 6 wild-type male mice were taken as the control group. The mice in the treatment group were treated with EA (continuous wave, 2 Hz of frequency) at "Baihui" (GV 20) and bilateral "Shenshu" (BL 23), once a day; 7-day treatment was taken as a course of treatment, and 2 courses of treatment were given. The immunohistochemistry method and Western blot method were used to detect the distribution and expression level of hippocampal PI3K/GSK3α signal pathway related proteins P85α, P110α, GSK3α and pS21GSK3α, and the number of hippocampal senile plaques (SP) was observed. RESULTS: The proteins of P85α, P110α, GSK3α and pS21GSK3α were mainly distributed in the cytoplasm of hippocampal neurons, and the GSK3α was also distributed in the axons of neurons in the model group and the treatment group. The immunohistochemistry results showed that the distribution level of GSK3α in the hippocampus in the model group was significantly higher than that in the control group (P<0.001), and the distribution level of pS21GSK3α, P85α and P110α was significantly decreased (P<0.01, P<0.001); compared with the model group, the distribution level of GSK3α in the hippocampus in the treatment group was significantly decreased (P<0.001), and the distribution level of pS21GSK3α, P85α and P110α in hippocampus was significantly increased (P<0.05, P<0.001). The Western blot results showed compared with the control group, the expression of pS21GSK3α, P85α and P110α as well as the ratio of pS21GSK3α/GSK3α in the hippocampus in the model group were significantly decreased (P<0.001), and the expression of GSK3α was increased (P<0.05); compared with the model group, the expression of pS21GSK3α, P85α, P110α and the ratio of pS21GSK3α/GSK3α in the hippocampus in the treatment group were significantly increased (P<0.01, P<0.001), and the expression of GSK3α was decreased (P<0.05). Compared with the control group, the number of hippocampal SP in the model group was significantly increased (P<0.001); compared with the model group, the number of hippocampal SP in the treatment group was significantly decreased (P<0.01). CONCLUSION: EA could effectively regulate the expression of PI3K/GSK3α signal pathway related proteins in the hippocampus in mice with AD, so as to reduce the formation and deposition of SP.

16.
Mol Med Rep ; 22(1): 362-370, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32319653

RESUMO

Bacillus Calmette­Guérin (BCG) is considered to be a successful biotherapy for treating bladder cancer (BCa). However, the underlying mechanisms of BCG have not been completely clarified, to date. The role of macrophages in BCG therapy for BCa has still not been determined in vivo. In the present study, the role and potential mechanism of BCG (0.25, 1.25 and 6.25 µg/mouse; intravenous) immunotherapy for BCa was investigated in a NOD/scid IL2Rg­/­ (NSI) mouse model by targeting macrophages in vivo. Notably, it was observed that NSI mice with T24 BCa cells displayed high levels of the macrophage marker CD11b+ F4/80+ after injection via the tail vein of live BCG, as well as a significant reduction in tumor volume. The levels of the inflammatory and macrophage maturation cytokines, such as tumor necrosis factor­α, interleukin (IL)­1ß, IL­6, IL­12P70, TNF superfamily member 11 and monocyte chemotactic protein 1, were significantly increased in the serum and the tumor supernatant compared to that in normal control subjects. Furthermore, BCG promoted the expression of the pro­differential genes Spi­1 proto­oncogene, early growth response protein 1, nuclear factor (NF)­κB and proto­oncogene c­Fos in bone marrow. In conclusion, these observations indicate that the injection of live BCG can target macrophages against bladder tumor growth in vivo. The mechanism is likely related to the promotion of macrophage maturation, immune activation and increased numbers of macrophages infiltrating the bladder tumor.

18.
Int J Oncol ; 56(4): 909-920, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32319563

RESUMO

Oral squamous cell carcinoma (OSCC) is capable of constructing a favorable immune escape environment through interactions of cells with cells and of cells with the environment. Programmed death ligand­1 (PD­L1) is a well­recognized inhibitor of anti­tumor immunity that plays an important role in tumor immune escape. However, the molecular mechanisms regulating PD­L1 expression are not yet fully understood. In this study, to investigate the role of protein kinase D3 (PKD3) in the regulation of PD­L1 expression, the expression and correlation of PKD3 and PD­L1 were first analyzed by the immunostaining of human OSCC tissue sections, cell experiments and TCGA gene expression databases. The expression levels of PKD3 and PD­L1 were found to be significantly higher in OSCC cells than in normal tissues or cells. In addition, the expression levels of PKD3 and PD­L1 were found to be significantly positively correlated. Subsequently, it was found that the levsel of PD­L1 expression decreased following the silencing of PKD3 and that the ability of interferon (IFN)­Î³ to induce PD­L1 expression was also decreased in OSCC. The opposite phenomenon occurred following the overexpression of PKD3. It was also found that the phosphorylation of signal transducer and activator of transcription (STAT)1/STAT3 was reduced by the knockdown of PKD3 in OSCC. Moreover, the expression level of PD­L1 was decreased after the use of siRNA to knockdown STAT1 or STAT3. On the whole, the findings of this study confirm that PKD3 regulates the expression of PD­L1 induced by IFN­Î³ by regulating the phosphorylation of STAT1/STAT3. These findings broaden the understanding of the biological function of PKD3, suggesting that PKD is a potential therapeutic target for OSCC.

19.
Biol Res ; 53(1): 14, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32293550

RESUMO

BACKGROUND: Previous studies have shown that long noncoding RNA (lncRNA) LINC00483 was aberrantly expressed in human cancers, including gastric cancer. However, the regulatory mechanism of this lncRNA in gastric cancer remains largely unknown. The present study aimed to investigate the effect of LINC00483 on gastric cancer development and explore the potential regulatory network of LINC00483/microRNA (miR)-490-3p/mitogen-activated protein kinase 1 (MAPK1). METHODS: Thirty patients with gastric cancer were recruited for tissues collection. The expression levels of LINC00483, miR-490-3p and MAPK1 were detected by quantitative real-time polymerase chain reaction or western blot. Cell viability, apoptosis, migration and invasion were determined by MTT, flow cytometry, transwell assays and western blot, respectively. The target association between miR-490-3p and LINC00483 or MAPK1 was confirmed by luciferase reporter assay. Xenograft model was established to assess the function of LINC00483 in vivo. RESULTS: LINC00483 and MAPK1 levels were increased in gastric cancer tissues and cells. Knockdown of LINC00483 or MAPK1 inhibited cells viability, migration and invasion but promoted apoptosis in gastric cancer cells. Moreover, MAPK1 overexpression attenuated the effect of LINC00483 knockdown on gastric cancer development. LINC00483 could increase MAPK1 expression by competitively sponging miR-490-3p. miR-490-3p overexpression suppressed gastric cancer development, which was abated by introduction of LINC00483. Besides, inhibition of LINC00483 decreased xenograft tumor growth by regulating miR-490-3p/MAPK1 axis. CONCLUSION: Knockdown of LINC00483 inhibited gastric cancer development in vitro and in vivo by increasing miR-490-3p and decreasing MAPK1, elucidating a novel mechanism for understanding the development of gastric cancer.


Assuntos
MicroRNAs/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , RNA Longo não Codificante/metabolismo , Neoplasias Gástricas/metabolismo , Animais , Apoptose , Carcinogênese/metabolismo , Linhagem Celular Tumoral/metabolismo , Movimento Celular , Sobrevivência Celular , Células Epiteliais/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Luciferases/metabolismo , Masculino , Camundongos Endogâmicos BALB C , MicroRNAs/genética , RNA Longo não Codificante/genética , Neoplasias Gástricas/genética , Ensaios Antitumorais Modelo de Xenoenxerto
20.
J Virol ; 94(12)2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32238587

RESUMO

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.

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