Article
Virology
Feifei Diao, Juan Bai, Chenlong Jiang, Yangyang Sun, Yanni Gao, Hans Nauwynck, Ping Jiang, Xing Liu
Summary: This study reveals that stimulator of interferon genes (STING) suppresses the replication of porcine reproductive and respiratory syndrome virus (PRRSV) through type I interferon signaling. However, PRRSV can inhibit STING function by impeding its translocation. Moreover, the nonstructural protein 2 (Nsp2) of PRRSV interacts with STING and disrupts its function. Additionally, PRRSV Nsp2 retains STING at the endoplasmic reticulum by increasing the level of STIM1 protein.
JOURNAL OF VIROLOGY
(2023)
Article
Veterinary Sciences
Mengmeng Zhao, Huiyang Sha, Hang Zhang, Ruining Wang
Summary: This study found that TRIM4 gene inhibits the proliferation of PRRSV through ubiquitination and degradation of the NSP2 protein, providing a new insight for the development of new antiviral targets.
BMC VETERINARY RESEARCH
(2022)
Article
Immunology
Li Du, Honglei Wang, Fang Liu, Zeyu Wei, Changjiang Weng, Jun Tang, Wen-hai Feng
Summary: Highly pathogenic PRRSV infection leads to up-regulation of COX-2 and PGE2 production in microglia through NSP2 protein interaction with 14-3-3 zeta, essential amino acid residues identified for this process. Mutant viruses lacking these residues show impaired ability to induce fever and clinical symptoms in pigs, suggesting potential for development of attenuated vaccines.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Microbiology
Lujia Zhou, Yang Yang, Qiqi Xia, Zhixin Guan, Junjie Zhang, Beibei Li, Yafeng Qiu, Ke Liu, Donghua Shao, Zhiyong Ma, Xiaodu Wang, Jianchao Wei
Summary: PRRS is an immunosuppressive disease in pigs caused by PRRSV, leading to reproductive and respiratory disorders. The predominant strain in Eastern China is still highly pathogenic PRRSV, with an increasing proportion of NADC30-like and NADC34-like strains. This study enriches the epidemiological data and provides a theoretical basis for the development of vaccines and prevention and control of the disease.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Microbiology
Min-A Lee, Usharani Jayaramaiah, Su-Hwa You, Eun-Gyeong Shin, Seung-Min Song, Lanjeong Ju, Seok-Jin Kang, Bang-Hun Hyun, Hyang-Sim Lee
Summary: This study collected serum and tissue samples between 2018 and 2022 to analyze the PRRSV types in Korea. Subgroup A was the most prevalent, followed by lineage 1, lineage 5, LKC, LKB, and subtype 1C. Highly virulent lineages 1 and 8 were detected, which can mutate or recombine with other viruses. The current vaccine in Korea offers limited protection, emphasizing the need for ongoing surveillance and region-specific immunization programs to reduce PRRSV infections.
Article
Virology
Liubov Cherkashchenko, Kai Rausalu, Sanjay Basu, Luke Alphey, Andres Merits
Summary: Alphaviruses, which are primarily transmitted by mosquitoes, induce resistance to superinfection in infected cells through the blockage of RNA replication. The replication proteins of alphaviruses, nsP1-4, are produced from nonstructural polyprotein precursors and are processed by the protease activity of nsP2. Studies on the effects of nsP2 on alphavirus RNA replication using trans-replicase systems and replicon vectors demonstrated that nsP2 reduces the RNA replicase activity of the homologous virus. This inhibitory effect is partially dependent on the protease active site of nsP2. Mutations in the replicase polyprotein that prevent its cleavage by nsP2 attenuate the negative effect of nsP2, indicating that nsP2-mediated inhibition of RNA replicase activity is primarily due to its protease activity. Moreover, co-expression of nsP2 also suppresses the replicase activity of heterologous alphaviruses. Overall, these findings enhance our understanding of the mechanisms underlying superinfection exclusion in alphaviruses and may facilitate the development of anti-alphavirus strategies.
Article
Immunology
Chang-zhan Xie, Zheng Wang, Zhuo Ha, Ying Zhang, Yu-biao Xie, He Zhang, Fu-long Nan, Jin-yong Zhang, Guan-yu Zhao, Zhuo-xin Li, Cheng-hui Li, Cheng-dong Yu, Ping Zhang, Hui-jun Lu, Ning-yi Jin
Summary: The study identified a new PRRSV strain, PRRSV-HB-16-China-2019, in China, which is a novel NSP2-deletion NADC30-like strain with specific deletions and mutations. This strain, recombined between a NADC30-like strain and a vaccine strain, poses a challenge to PRRSV prevention in China.
MICROBIAL PATHOGENESIS
(2021)
Article
Virology
Xin Hu, Elaine Morazzani, Jaimee R. Compton, Moeshia Harmon, Veronica Soloveva, Pamela J. Glass, Andres Dulcey Garcia, Juan J. Marugan, Patricia M. Legler
Summary: Two epoxysuccinyl prodrugs and a reversible oxindole inhibitor were found to inhibit the Venezuelan equine encephalitis virus (VEEV) nonstructural protein 2 (nsP2). Further studies showed that these inhibitors could effectively reduce viral replication and viral titers in vivo.
Article
Veterinary Sciences
Chang-Zhan Xie, Yi-Mo Tao, Zhuo Ha, Ping Zhang, Ying Zhang, He Zhang, Ning-Yi Jin, Hui-Jun Lu
Summary: This study provides valuable evidence for understanding the genomic characteristics and potential pathogenicity of the NADC34-like strain 2020-Acheng-1.
RESEARCH IN VETERINARY SCIENCE
(2022)
Article
Multidisciplinary Sciences
Sushil Kumar, Gourav Choudhir, Sakshi Sharma, Y. Vimala, Nidhi Joshi, Abhay Tiwari, Garima Singh, Mohammad Javed Ansari, Mohd Khalizan Sabullah, R. Z. Sayyed, Tahani Awad Alahmadi
Summary: This study identified four bioactive metabolites from Nigella sativa as potential inhibitors of the chikungunya virus. Through molecular docking and dynamics simulation, these metabolites showed promising results and could be strong candidates for drug development.
JOURNAL OF KING SAUD UNIVERSITY SCIENCE
(2023)
Review
Oncology
Gilles Lalmanach, Mariana Kasabova-Arjomand, Fabien Lecaille, Ahlame Saidi
Summary: Cystatin M/E, a low molecular mass protein, exhibits both tumor-suppressing and tumor-promoting effects in various cancers. Understanding the regulatory mechanisms of Cystatin M/E and its expression and activity in tumorigenesis is crucial in maintaining proteolytic balance and addressing its imbalance in cancer.
Article
Biochemistry & Molecular Biology
Hari Priya Parameshwaran, Kesavan Babu, Christine Tran, Kevin Guan, Aleique Allen, Venkatesan Kathiresan, Peter Z. Qin, Rakhi Rajan
Summary: The study on the BH variant of Cas12a from Francisella novicida reveals the role of the bridge helix in substrate selectivity, affecting both RNA-guided DNA cleavage in cis-activity and trans-single-stranded DNA cleavage activity. This highlights the conservation of the bridge helix in target discrimination among Cas nucleases.
Article
Virology
Can Kong, Dan Li, Yanxin Hu, Peng Gao, Yongning Zhang, Lei Zhou, Xinna Ge, Xin Guo, Jun Han, Hanchun Yang
Summary: Porcine reproductive and respiratory syndrome virus (PRRSV) is a major threat to the world swine industry. Genetic variations within the nsp2 region present an intriguing conundrum to PRRSV biology and pathogenesis. By constructing chimeric mutants, this study highlights the significance of nsp2 genetic variation in modulating PRRSV virulence and persistence via immune modulation.
JOURNAL OF VIROLOGY
(2023)
Article
Pharmacology & Pharmacy
Yu-Jen Chang, Uyen Nguyen Phuong Le, Jia-Jun Liu, Sin-Rong Li, Shao-Ting Chao, Hsueh-Chou Lai, Yu-Feng Lin, Kai-Cheng Hsu, Chih-Hao Lu, Cheng-Wen Lin
Summary: This study used an in-silico prediction approach to investigate potential inhibitory compounds against SARS-CoV-2 Mpro. Compound NSC89640 (coded C1) showed marked inhibitory activity, and compound NSC89641 (coded D2) exhibited the highest inhibitory potency against SARS-CoV-2 Mpro. Both C1 and D2 also displayed inhibitory activity against MERS-CoV.
ANTIVIRAL RESEARCH
(2023)
Article
Chemistry, Medicinal
Matthew E. Cuellar, Mu Yang, Surendra Karavadhi, Ya-Qin Zhang, Hu Zhu, Hongmao Sun, Min Shen, Matthew D. Hall, Samarjit Patnaik, Karen H. Ashe, Michael A. Walters, Steffen Pockes
Summary: Recent Alzheimer's research has focused on the Casp2 enzyme, but the existing Casp2 inhibitors face challenges for use as CNS drugs. This study successfully screened a chloroacetamide-based fragment library and identified 64 Casp2 hits with selectivity over Casp3. Compounds with inhibition values in the micromolar and sub-micromolar range, as well as selectivity for Casp2 over Casp3, were discovered. The findings pave the way for the future development of small-molecule Casp2 inhibitors.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Virology
Ruiqi Sun, Yanyu Guo, Xiaoyang Li, Ruiqiao Li, Jingxuan Shi, Zheng Tan, Lilin Zhang, Lei Zhang, Jun Han, Jinhai Huang
Summary: Ubiquitination plays a major role in immune regulation after viral infection. This study identifies a porcine E3 ubiquitin ligase RNF122 that is upregulated in PRRSV-infected cells and promotes PRRSV infection. RNF122 mediates K63-linked ubiquitination of PRRSV nsp4 protein to enhance its stability, contributing to virus replication. Additionally, RNF122 also ubiquitinates MDA5 to degrade it and inhibit IFN production, ultimately promoting virus proliferation. This study provides new insights into the immune escape mechanisms of PRRSV and may contribute to the development of antiviral drugs.
Article
Virology
Xintan Yang, Shengkui Xu, Dengjin Chen, Ruijiao Jiang, Haoran Kang, Xinna Ge, Lei Zhou, Jun Han, Yongning Zhang, Xin Guo, Hanchun Yang
Summary: Pseudorabies virus (PRV), also known as suid herpesvirus 1 (SuHV-1), is a highly devastating swine pathogen in China. The sudden emergence of PRV variants in 2011, with higher pathogenicity and cross-species transmission potential, has caused significant economic losses and posed a threat to public health. In this study, a Tandem Mass Tag (TMT)-based proteomic analysis was conducted to quantitatively screen for differentially expressed cellular proteins in PRV-infected Vero cells. A total of 7072 proteins were identified, with 960 proteins showing significant regulation, including 89 upregulated and 871 downregulated proteins. The differentially expressed proteins were involved in various biological processes and signaling pathways, providing insights into the pathogenesis of PRV variants and potential targets for pseudorabies prevention.
Article
Virology
Hang Gao, Zhaoying Xiang, Xinna Ge, Lei Zhou, Jun Han, Xin Guo, Yanhong Chen, Yongning Zhang, Hanchun Yang
Summary: This study analyzed the dynamic changes in the proteome of PK-15 cells during Senecavirus A (SVA) infection using tandem mass tags (TMT) labeling coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). The results showed significant differential expression of proteins at different time points of infection, with these proteins mainly involved in host immune responses and metabolic processes. In addition, the study demonstrated that Mx1 protein exerts antiviral activity against SVA by interacting with VP1 and VP2 proteins.
Article
Microbiology
Xixi Gui, Wuchao Zhang, Peng Gao, Yongning Zhang, Lei Zhou, Xinna Ge, Xin Guo, John W. Wills, Jun Han, Hanchun Yang
Summary: This study reports a previously unrecognized aberrant form of glycoprotein I (gl) in HSV-1-infected cells. This aberrant gl has a unique migration behavior and stable fold, contributing to its abnormal molecular size. These findings have important implications in understanding viral spread and pathogenesis.
MICROBIOLOGY SPECTRUM
(2022)
Article
Agriculture, Dairy & Animal Science
Dengjin Chen, Yi Huang, Yating Guo, Lihong Wang, Yongning Zhang, Lei Zhou, Xinna Ge, Jun Han, Xin Guo, Hanchun Yang
Summary: PCV3 infection is prevalent in pig populations in China, with high variability in different provinces. PCV3a and PCV3b are the predominant subtypes in the studied regions. These findings provide important insights into the epidemiology and evolution of PCV3 in China and will guide future efforts to prevent and control the disease.
Article
Microbiology
Yang Wang, Xinna Ge, Yongning Zhang, Xin Guo, Jun Han, Lei Zhou, Hanchun Yang
Summary: Porcine reproductive and respiratory syndrome virus (PRRSV) is a major pathogen in the global pork industry. Researchers have developed a DNA-tagged virus for high-throughput screening and evaluation of anti-PRRSV therapies. This tagged virus can be used to study viral propagation and growth in vitro and in vivo, as well as for a novel virus neutralization assay.
MICROBIOLOGY SPECTRUM
(2022)
Article
Microbiology
Jingjing Wang, Mengsi Zhang, Xiaochun Cui, Xiang Gao, Weifeng Sun, Xinna Ge, Yongning Zhang, Xin Guo, Jun Han, Lei Zhou, Hanchun Yang
Summary: This study provides direct scientific evidence for the reversion to virulence of PRRS MLV and offers valuable clues for exploring its molecular mechanism.
MICROBIOLOGY SPECTRUM
(2022)
Article
Virology
Can Kong, Dan Li, Yanxin Hu, Peng Gao, Yongning Zhang, Lei Zhou, Xinna Ge, Xin Guo, Jun Han, Hanchun Yang
Summary: Porcine reproductive and respiratory syndrome virus (PRRSV) is a major threat to the world swine industry. Genetic variations within the nsp2 region present an intriguing conundrum to PRRSV biology and pathogenesis. By constructing chimeric mutants, this study highlights the significance of nsp2 genetic variation in modulating PRRSV virulence and persistence via immune modulation.
JOURNAL OF VIROLOGY
(2023)