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https://www.readbyqxmd.com/read/29327729/h5n1-influenza-virus-specific-mirna-like-small-rna-increases-cytokine-production-and-mouse-mortality-via-targeting-poly-rc-binding-protein-2
#1
Xihan Li, Zheng Fu, Hongwei Liang, Yanbo Wang, Xian Qi, Meng Ding, Xinlei Sun, Zhen Zhou, Ying Huang, Hongwei Gu, Limin Li, Xi Chen, Donghai Li, Quan Zhao, Fenyong Liu, Hua Wang, Jin Wang, Ke Zen, Chen-Yu Zhang
Infection of H5N1 influenza virus causes the highest mortality among all influenza viruses. The mechanisms underlying such high viral pathogenicity are incompletely understood. Here, we report that the H5N1 influenza virus encodes a microRNA-like small RNA, miR-HA-3p, which is processed from a stem loop-containing viral RNA precursor by Argonaute 2, and plays a role in enhancing cytokine production during H5N1 infection. Mechanistic study shows that miR-HA-3p targets poly(rC)-binding protein 2 (PCBP2) and suppresses its expression...
January 12, 2018: Cell Research
https://www.readbyqxmd.com/read/29321315/paramyxovirus-v-proteins-interact-with-the-rig-i-trim25-regulatory-complex-and-inhibit-rig-i-signaling
#2
Maria T Sanchez-Aparicio, Leighland J Feinman, Adolfo García-Sastre, Megan L Shaw
Paramyxovirus V proteins are known antagonists of the RIG-I-like receptor (RLR)-mediated interferon induction pathway, interacting with and inhibiting the RLR MDA5. We report interactions between the Nipah virus V protein and both the RIG-I regulatory protein, TRIM25, and RIG-I. We also observed interactions between these host proteins and the V proteins of measles virus, Sendai virus and parainfluenza virus. These interactions are mediated by the conserved C-terminal domain of the V protein, which binds to the tandem CARDs of RIG-I (the region of TRIM25-ubiquitination) and to the SPRY domain of TRIM25, which mediates TRIM25 interaction with the RIG-I CARDs...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29317664/human-cytomegalovirus-encoded-us9-targets-mavs-and-sting-signaling-to-evade-type-i-interferon-immune-responses
#3
Hyun Jin Choi, Areum Park, Sujin Kang, Eunhye Lee, Taeyun A Lee, Eun A Ra, Jiseon Lee, Sungwook Lee, Boyoun Park
Human cytomegalovirus (HCMV) has evolved sophisticated immune evasion mechanisms that target both the innate and adaptive immune responses. However, how HCMV encoded proteins are involved in this immune escape is not clear. Here, we show that HCMV glycoprotein US9 inhibits the IFN-β response by targeting the mitochondrial antiviral-signaling protein (MAVS) and stimulator of interferon genes (STING)-mediated signaling pathways. US9 accumulation in mitochondria attenuates the mitochondrial membrane potential, leading to promotion of MAVS leakage from the mitochondria...
January 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/29285277/indirubin-a-bisindole-alkaloid-from-isatis-indigotica-reduces-h1n1-susceptibility-in-stressed-mice-by-regulating-mavs-signaling
#4
Chong Jie, Zhuo Luo, Huan Chen, Min Wang, Chang Yan, Zhong-Fu Mao, Gao-Keng Xiao, Hiroshi Kurihara, Yi-Fang Li, Rong-Rong He
Isatis indigotica has a long history in treating virus infection and related symptoms in China. Nevertheless, its antivirus evidence in animal studies is not satisfactory, which might be due to the lack of appropriate animal model. Previously, we had utilized restraint stress to establish mouse H1N1 susceptibility model which was helpful in evaluating the anti-virus effect of medicines targeting host factors, such as type I interferon production. In this study, this model was employed to investigate the effect and mechanism of indirubin, a natural bisindole alkaloid from Isatis indigotica, on influenza A virus susceptibility...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29280086/negative-regulation-of-mavs-mediated-innate-immune-response-by-asc
#5
Yue Han, Xiang He, Congwen Wei, Ting Song, Ling Zou, Zihui Li, Jiazhou Ye, Lunan Qi, Lequn Li, Hui Zhong, Feixiang Wu
Stringent control of the type I interferon signaling pathways is critical to effective host immune responses, however, the molecular mechanisms that negatively regulate these pathways are still poorly understood. Here, we show that apoptosis speck-like protein (ASC), an adaptor protein of inflammasome complex, can inhibit IFN-β signaling response by interacting with mitochondrial antiviral signaling protein (MAVS). Importantly, ASC-specific siRNA knockdown enhanced virus-induced type I interferon production, with consequent reduction of virus replication...
December 26, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29245018/regulation-of-mavs-activation-through-post-translational-modifications
#6
REVIEW
Bingyu Liu, Chengjiang Gao
RLRs (including RIG-I and MDA5) are the main receptors that recognize cytoplasmic viral RNA. Upon binding of viral RNA, RIG-I and MDA5 recruit mitochondria-localized MAVS to activate the downstream antiviral signaling. MAVS forms prion-like aggregates on the mitochondria after virus infection. The regulatory mechanisms for MAVS activation have been defined in various studies. Here, we summarize the recent advances about MAVS roles in antiviral immunity, discuss the regulation of MAVS activation, and suggest interesting areas for future research...
December 12, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/29244871/inflammatory-monocytes-mediate-control-of-acute-alphavirus-infection-in-mice
#7
Kelsey C Haist, Kristina S Burrack, Bennett J Davenport, Thomas E Morrison
Chikungunya virus (CHIKV) and Ross River virus (RRV) are mosquito-transmitted alphaviruses that cause debilitating acute and chronic musculoskeletal disease. Monocytes are implicated in the pathogenesis of these infections; however, their specific roles are not well defined. To investigate the role of inflammatory Ly6ChiCCR2+ monocytes in alphavirus pathogenesis, we used CCR2-DTR transgenic mice, enabling depletion of these cells by administration of diptheria toxin (DT). DT-treated CCR2-DTR mice displayed more severe disease following CHIKV and RRV infection and had fewer Ly6Chi monocytes and NK cells in circulation and muscle tissue compared with DT-treated WT mice...
December 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29230364/complete-genome-sequence-and-comparative-genomics-of-the-golden-pompano-trachinotus-ovatus-pathogen-vibrio-harveyi-strain-qt520
#8
Zhigang Tu, Hongyue Li, Xiang Zhang, Yun Sun, Yongcan Zhou
Vibrio harveyi is a Gram-negative, halophilic bacterium that is an opportunistic pathogen of commercially farmed marine vertebrate species. To understand the pathogenicity of this species, the genome of V. harveyi QT520 was analyzed and compared to that of other strains. The results showed the genome of QT520 has two unique circular chromosomes and three endogenous plasmids, totaling 6,070,846 bp with a 45% GC content, 5,701 predicted ORFs, 134 tRNAs and 37 rRNAs. Common virulence factors, including ACF, IlpA, OmpU, Flagellin, Cya, Hemolysin and MARTX, were detected in the genome, which are likely responsible for the virulence of QT520...
2017: PeerJ
https://www.readbyqxmd.com/read/29207503/detection-of-nuclear-protein-profile-changes-by-human-metapneumovirus-m2-2-protein-using-quantitative-differential-proteomics
#9
Yuping Ren, Eunjin Choi, Ke Zhang, Yu Chen, Sha Ye, Xiaoling Deng, Kangling Zhang, Xiaoyong Bao
Human metapneumovirus (hMPV) is a leading cause of lower respiratory infection in pediatric populations globally. This study examined proteomic profile changes in A549 cells infected with hMPV and two attenuated mutants with deleted PDZ domain-binding motif(s) in the M2-2 protein. These motifs are involved in the interruption of antiviral signaling, namely the interaction between the TNF receptor associated factor (TRAF) and mitochondrial antiviral-signaling (MAVS) proteins. The aim of this study was to provide insight into the overall and novel impact of M2-2 motifs on cellular responses via an unbiased comparison...
December 3, 2017: Vaccines
https://www.readbyqxmd.com/read/29194722/the-rna-genome-of-hepatitis-e-virus-robustly-triggers-antiviral-interferon-response
#10
Wenshi Wang, Yijin Wang, Changbo Qu, Shan Wang, Jianhua Zhou, Wanlu Cao, Lei Xu, Buyun Ma, Mohamad S Hakim, Yuebang Yin, Tiancheng Li, Maikel P Peppelenbosch, Jingmin Zhao, Qiuwei Pan
The outcomes of hepatitis E virus (HEV) infection are diverse, ranging from asymptomatic carrier, self-limiting acute infection, fulminant hepatitis to persistent infection. This is closely associated with the immunological status of the host. This study aims to understand the innate cellular immunity as the first-line defense mechanisms in response to HEV infection. Phosphorylation of STAT1, a hallmark of the activation of antiviral interferon (IFN) response, was observed in the liver tissues of majority of HEV infected patients, but not in the liver of uninfected individuals...
December 1, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29182965/real-time-continuous-recognition-of-knee-motion-using-multi-channel-mechanomyography-signals-detected-on-clothes
#11
Haifeng Wu, Daqing Wang, Qing Huang, Lifu Gao
Mechanomyography (MMG) signal has been recently investigated for pattern recognition of human motion. In theory, it is no need of direct skin contact to be detected and unaffected by changes in skin impedance. So, it is hopeful for developing wearable sensing device with clothes. However, there have been no studies so far to detect MMG signal on clothes and verify the feasibility of pattern recognition. For this study, 4-channel MMG signals were detected on clothes from the thigh muscles of 8 able-bodied participants...
November 23, 2017: Journal of Electromyography and Kinesiology
https://www.readbyqxmd.com/read/29177867/detection-and-quantification-of-mavs-aggregation-via-confocal-microscopy
#12
Tan A Nguyen, Lachlan Whitehead, Ken C Pang
During infection, the cytosolic detection of viral double-stranded RNA (dsRNA) leads to the oligomerization and activation of mitochondrial antiviral signaling protein (MAVS) and the subsequent production of type I interferon (IFN). Here, we describe a novel method of visualizing and quantifying the aggregation of MAVS in response to dsRNA stimulation or viral infection in vitro using confocal microscopy.
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29165031/bst2-inhibits-type-i-ifn-interferon-signaling-by-accelerating-mavs-degradation-through-calcoco2-directed-autophagy
#13
Shouheng Jin, Jun Cui
Macroautophagy/autophagy is a conserved lysosomal degradation system that breaks down intracellular material through the formation of double-membrane autophagosomes in eukaryotic cells. Cargo receptors have been illustrated to play essential roles in capturing and delivering specific substrates into phagophores, the precursors to autophagosomes, for degradation. However, the detailed mechanism underlying selective recognition of the substrates for autophagic degradation remains poorly understood. Recently, we have revealed that IFN (interferon)-induced BST2 recruits the E3 ubiquitin ligase MARCH8 to catalyze the K27-linked ubiquitination of MAVS for CALCOCO2-directed autophagic degradation, hence inhibiting DDX58-mediated type I interferon signaling through a negative feedback loop...
December 31, 2017: Autophagy
https://www.readbyqxmd.com/read/29155878/irhom2-is-essential-for-innate-immunity-to-rna-virus-by-antagonizing-er-and-mitochondria-associated-degradation-of-visa
#14
Wei-Wei Luo, Shu Li, Chen Li, Zhou-Qin Zheng, Pan Cao, Zhen Tong, Huan Lian, Su-Yun Wang, Hong-Bing Shu, Yan-Yi Wang
VISA (also known as MAVS, IPS-1 and Cardif) is an essential adaptor protein in innate immune response to RNA virus. The protein level of VISA is delicately regulated before and after viral infection to ensure the optimal activation and timely termination of innate antiviral response. It has been reported that several E3 ubiquitin ligases can mediate the degradation of VISA, but how the stability of VISA is maintained before and after viral infection remains enigmatic. In this study, we found that the ER-associated inactive rhomboid protein 2 (iRhom2) plays an essential role in mounting an efficient innate immune response to RNA virus by maintaining the stability of VISA through distinct mechanisms...
November 20, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29141203/mouse-adenovirus-type-1-infection-of-adipose-tissue
#15
Caitlyn T Molloy, Laura J Adkins, Cameron Griffin, Kanakadurga Singer, Jason B Weinberg
Human adenovirus (HAdV) type 36 seropositivity has been linked to obesity in humans. That link is supported by a small number of studies using HAdV-36 infection of animals that are not natural hosts for HAdVs. In this study, we infected mice with mouse adenovirus type 1 (MAV-1), a mouse pathogen, to determine whether MAV-1 infected adipose tissue and was associated with adipose tissue inflammation and obesity. We detected MAV-1 in adipose tissue during acute MAV-1 infection, but we did not detect virus-induced increases in adipose tissue cytokine expression or histological evidence of adipose tissue inflammation during acute infection...
November 12, 2017: Virus Research
https://www.readbyqxmd.com/read/29132350/avian-infectious-bronchitis-virus-disrupts-the-melanoma-differentiation-associated-gene-5-mda5-signaling-pathway-by-cleavage-of-the-adaptor-protein-mavs
#16
Liping Yu, Xiaorong Zhang, Tianqi Wu, Jin Su, Yuyang Wang, Yuexin Wang, Baoyang Ruan, Xiaosai Niu, Yantao Wu
BACKGROUND: Melanoma differentiation associated gene 5 (MDA5) and retinoic acid-inducible gene-I (RIG-I) selectively sense cytoplasmic viral RNA to induce an antiviral immune response. Infectious bronchitis virus (IBV) is one of the most important infectious agents in chickens, and in chicken cells, it can be recognized by MDA5 to activate interferon production. RIG-I is considered to be absent in chickens. However, the absence of RIG-I in chickens raises the question of whether this protein influences the antiviral immune response against IBV infection...
November 13, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/29125880/mavs-activates-tbk1-and-ikk%C3%AE%C2%B5-through-trafs-in-nemo-dependent-and-independent-manner
#17
Run Fang, Qifei Jiang, Xiang Zhou, Chenguang Wang, Yukun Guan, Jianli Tao, Jianzhong Xi, Ji-Ming Feng, Zhengfan Jiang
Mitochondrial antiviral-signaling protein (MAVS) transmits signals from RIG-I-like receptors after RNA virus infections. However, the mechanism by which MAVS activates downstream components, such as TBK1 and IKKα/β, is unclear, although previous work suggests the involvement of NEMO or TBK1-binding proteins TANK, NAP1, and SINTBAD. Here, we report that MAVS-mediated innate immune activation is dependent on TRAFs, partially on NEMO, but not on TBK1-binding proteins. MAVS recruited TBK1/IKKε by TRAFs that were pre-associated with TBK1/IKKε via direct interaction between the coiled-coil domain of TRAFs and the SDD domain of TBK1/IKKε...
November 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29117566/cytosolic-recognition-of-rna-drives-the-immune-response-to-heterologous-erythrocytes
#18
Claudia Loetsch, Joanna Warren, Adrienne Laskowski, Rodrigo Vazquez-Lombardi, Christoph Jandl, David B Langley, Daniel Christ, David R Thorburn, David K Ryugo, Jonathan Sprent, Marcel Batten, Cecile King
The archetypal T cell-dependent antigen is sheep red blood cells (SRBCs), which have defined much of what we know about humoral immunity. Early studies using solubilized or sonicated SRBCs argued that the intact structure of SRBCs was important for optimal antibody responses. However, the reason for the requirement of intact SRBCs for the response to polyvalent protein antigen remained unknown. Here, we report that the immune response to SRBCs is driven by cytosolic recognition of SRBC RNA through the RIG-I-like receptor (RLR)-mitochondrial anti-viral signaling adaptor (MAVS) pathway...
November 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/29102119/rig-1-and-mda-5-signaling-pathways-contribute-to-ifn-%C3%AE-production-and-viral-replication-in-porcine-circovirus-virus-type-2-infected-pk-15-cells-in-vitro
#19
Bei Huang, Jiansheng Li, Xinchen Zhang, Qiling Zhao, Mingqing Lu, Yingjun Lv
Type I Interferons (IFNs) is known for its antiviral activity; however, it is surprising that in vitro treatment of IFN-α and IFN-γ enhanced the replication of porcine circovirus type 2 (PCV2), indicating a complex relationship between interferon and PCV2. To date, it remains poorly understood how the interferon is produced during PCV2 infection and whether the interferon induced by PCV2 itself can promote viral replication. In this study, PCV2 induced the up-regulation of IFN-β in PK-15 cells, while treatment of PCV2-infected cells with the interferon regulatory factor-3 (IRF3) inhibitor, BX795, decreased the expression of IFN-β, whereas treatment with the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) inhibitor, BAY11-7082, did not...
November 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/29100916/molecular-characterization-ontogeny-and-expression-profiling-of-mitochondrial-antiviral-signaling-adapter-mavs-from-asian-seabass-lates-calcarifer-bloch-1790
#20
Rahul Krishnan, P Girish Babu, K Jeena, Gayathri Tripathi, Kurcheti Pani Prasad
Mitochondrial antiviral signaling protein (MAVS), an innate immune signaling adapter coordinates the signals received from two independent cytosolic pathogen recognition receptors (RIG-1 and MDA5) to induce antiviral genes. In the present study the MAVS gene of Lates calcarifer (LcMAVS) was cloned and characterized. The complete cDNA sequence of LcMAVS was 3160 bp and encodes a poly peptide of 577 amino acids. Structural analysis of LcMAVS revealed an N-terminal CARD-like domain, central proline-rich domain and a C-terminal transmembrane domain...
October 31, 2017: Developmental and Comparative Immunology
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