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virus nonstructural protein

J von Felden, J Vermehren, P Ingiliz, S Mauss, T Lutz, K G Simon, H W Busch, A Baumgarten, K Schewe, D Hueppe, C Boesecke, J K Rockstroh, M Daeumer, N Luebke, J Timm, J Schulze Zur Wiesch, C Sarrazin, S Christensen
BACKGROUND: Twelve weeks of the pangenotypic direct-acting antiviral (DAA) combination sofosbuvir/velpatasvir (SOF/VEL) was highly efficient in patients with hepatitis C virus (HCV) genotype 3 (GT3) infection in the ASTRAL-3 approval study. However, presence of resistance-associated substitutions (RASs) in the HCV nonstructural protein 5A (NS5A) was associated with lower treatment response. AIM: To assess the efficacy and safety of SOF/VEL ± ribavirin (RBV) and the impact of NS5A RASs and RBV use on treatment outcome in HCV GT3 infection in a real-world setting...
March 14, 2018: Alimentary Pharmacology & Therapeutics
Fei Xiao, Stanley Wang, Rina Barouch-Bentov, Gregory Neveu, Szuyuan Pu, Melanie Beer, Stanford Schor, Sathish Kumar, Vlad Nicolaescu, Brett D Lindenbach, Glenn Randall, Shirit Einav
Hepatitis C virus (HCV) spreads via secreted cell-free particles or direct cell-to-cell transmission. Yet, virus-host determinants governing differential intracellular trafficking of cell-free- and cell-to-cell-transmitted virus remain unknown. The host adaptor proteins (APs) AP-1A, AP-1B, and AP-4 traffic in post-Golgi compartments, and the latter two are implicated in basolateral sorting. We reported that AP-1A mediates HCV trafficking during release, whereas the endocytic adaptor AP-2 mediates entry and assembly...
March 13, 2018: MBio
Shifeng Ling, Mingyang Luo, Shengnan Jiang, Jiayu Liu, Chunying Ding, Qinghuan Zhang, Huancheng Guo, Wenjie Gong, Changchun Tu, Jinfu Sun
Classical swine fever virus (CSFV) nonstructural protein NS5A is a multifunctional protein functioning in regulation of viral genome replication, protein translation and assembly by interaction with viral or host proteins. Here, heat shock protein 27 (Hsp27) has been identified as a novel binding partner of NS5A by using His tag "pull down" coupled with shotgun LC-MS/MS, with interaction of both proteins further confirmed by co-immunoprecipitation and laser confocal assays. In PK-15 cells, silencing of Hsp27 expression by siRNA enhanced CSFV replication, and upregulation of Hsp27 inhibited viral proliferation...
March 8, 2018: Virology
Kanjana Srisutthisamphan, Krit Jirakanwisal, Suwipa Ramphan, Natthida Tongluan, Atichat Kuadkitkan, Duncan R Smith
Infections with the mosquito-borne dengue virus (DENV) remain a significant public health challenge. In the absence of a commercial therapeutic to treat DENV infection, a greater understanding of the processes of cellular replication is required. The abundant cellular chaperone protein heat shock protein 90 (Hsp90) has been shown to play a proviral role in the replication cycle of several viruses, predominantly through the stabilization of specific viral proteins. To investigate any potential role of Hsp90 in DENV infection the interaction between Hsp90 and DENV proteins was determined through co-immunoprecipitation experiments...
March 9, 2018: Scientific Reports
Zhenjian He, Jiahui Chen, Shu An, Xinhuai Dong, Jianchen Yu, Shihao Zhang, Yun Wu, Ge Li, Yu Zhang, Jueheng Wu, Xun Zhu, Mengfeng Li
Zika virus (ZIKV) is a mosquito-borne virus that has been identified as a cause of several severe disease manifestations, including congenital microcephaly and Guillain-Barré syndrome, meningoencephalitis and myelitis. Previous studies showed that ZIKV-infected patients exhibited elevated plasma levels of interleukin-1β (IL-1β), indicating that ZIKV may activate inflammasomes. However, the molecular basis for its viral pathogenesis remains poorly understood. In this current study, we found that ZIKV infection caused severe inflammatory pathological changes and promoted IL-1β production in vitro as well as in vivo...
March 6, 2018: Journal of Infectious Diseases
Rachel D Brownlee, Amir Ardeshir, Michael D Becker, April M Wagner, David G Besselsen
The influence of mouse strain, immune competence and age on the pathogenesis of a field strain of minute virus of mice (MVMm) was examined in BALB/c, C3H, C57BL/6 and SCID mice experimentally infected as neonates, weanlings and adults. Sera, bodily excretions and tissues were harvested at 7, 14, 28 and 56 days after inoculation and evaluated by serology, quantitative PCR and histopathology. Seroconversion to recombinant viral capsid protein 2 was consistently observed in all immunocompetent strains of mice, regardless of the age at which they were inoculated, while seroconversion to the viral nonstructural protein 1 was only consistently detected in neonate inoculates...
March 8, 2018: Journal of General Virology
Chi-Ping Chan, Chun-Kit Yuen, Pak-Hin Hinson Cheung, Sin-Yee Fung, Pak-Yin Lui, Honglin Chen, Kin-Hang Kok, Dong-Yan Jin
PACT is a double-stranded RNA-binding protein that has been implicated in host-influenza A virus (IAV) interaction. PACT facilitates the action of RIG-I in the activation of the type I IFN response, which is suppressed by the viral nonstructural protein NS1. PACT is also known to interact with the IAV RNA polymerase subunit PA. Exactly how PACT exerts its antiviral activity during IAV infection remains to be elucidated. In the current study, we demonstrated the interplay between PACT and IAV polymerase. Induction of IFN-β by the IAV RNP complex was most robust when both RIG-I and PACT were expressed...
March 7, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Yinghao Xin, Dang Wang, Meijin Huang, Jinjin Yu, Liurong Fang, Shaobo Xiao
Porcine reproductive and respiratory syndrome virus (PRRSV), an acute infectious disease agent in swine, causes enormous economic losses to the global swine industry. PRRSV nonstructural protein 1β (nsp1β) plays a critical role in viral subgenomic mRNA synthesis and host immune regulation. However, the global changes of cellular gene expression in natural target cells regulated by the nsp1β have not yet been identified. Here, isobaric tags for relative and absolute quantification (iTRAQ) labeling coupled with liquid chromatography-tandem mass spectrometry were used to quantitatively identify cellular proteins in porcine alveolar macrophage (PAM) 3D4/21 cells transduced with recombinant lentivirus expressing PRRSV nsp1β that are differentially expressed compared with PAM 3D4/21 cells transduced with recombinant lentivirus expressing GFP...
March 5, 2018: Virus Genes
Jo Ee Sam, Teak Sheng Gee, Nasser Abdul Wahab
Dengue fever has been a major cause of morbidity and mortality in subtropical and tropical countries. We report a rare case of severe dengue with spontaneous intracranial hemorrhage. A search of literature through PubMed revealed that the largest series analyzed so far only included five cases. A 47-year-old man presented with 7 days history of fever, headache, myalgia, and vomiting with hematemesis. On the day of presentation, he had reduced consciousness and an episode of generalized tonic-clonic seizure...
January 2018: Asian Journal of Neurosurgery
Krishnan Balasubramanian, Vaishali M Patil
We have carried out high-level quantum chemical computations followed by molecular docking studies on a set of 17C5 -arylidene rhodanine isomers to provide insights into the binding modes with different reported binding pockets of the nonstructural protein 5B (NS5B) polymerase that contribute to the hepatitis C virus (HCV) inhibition. We optimized the multi-target profile of the selected rhodanine analogs to investigate potential non-nucleotide inhibitors (NNIs) by quantum chemical optimization of the 18 isomers followed by docking with quantum chemically optimized structures of each isomer with NS5B polymerase at multiple binding pockets...
January 31, 2018: Computational Biology and Chemistry
Fumihiro Kato, Yuki Ishida, Akihiko Kawakami, Tomohiko Takasaki, Masayuki Saijo, Tomoyuki Miura, Takayuki Hishiki
Dengue virus (DENV) causes a wide range of illnesses in humans, including dengue fever and dengue haemorrhagic fever. Current animal models of DENV infection are limited for understanding infectious diseases in humans. Bonnet monkeys (Macaca radiata), a type of Old World monkey, have been used to study experimental and natural infections by flaviviruses, but Old World monkeys have not yet been used as DENV infection models. In this study, the replication levels of several DENV strains were evaluated using peripheral blood mononuclear cells...
February 21, 2018: Scientific Reports
Elise A Lamont, Erin Poulin, Srinand Sreevatsan, Maxim C-J Cheeran
Influenza A virus in swine (IAV-S) is a prevalent respiratory pathogen in pigs that has deleterious consequences to animal and human health. Pigs represent an important reservoir for influenza and potential mixing vessel for novel gene reassortments. Despite the central role of pigs in recent influenza outbreaks, much remains unknown about the impact of swine immunity on IAV-S transmission, pathogenesis, and evolution. An incomplete understanding of interactions between the porcine immune system and IAV-S has hindered development of new diagnostic tools and vaccines...
January 12, 2018: Journal of General Virology
Long Zhou, Runmin Kang, Bo Xie, Yiming Tian, Xin Yang, Jifeng Yu, Hongning Wang
The NADC30-like strains of porcine reproductive and respiratory syndrome virus (PRRSV) are characterized by a 131-amino-acid deletion in nonstructural protein 2 (NSP2). Here, we report the complete genome sequence of a recombinant NADC30-like PRRSV strain, SCnj16, that exhibits the molecular marker of the Chinese highly pathogenic PRRSV (HP-PRRSV) in NSP2.
February 8, 2018: Genome Announcements
D Wu, L Z Zhao, Y H Wu, H Zhang, M Zhang, Q Q Tan, H Q Zhou, F C Zhang, J F He
Objective: To investigate the sensitivity and specificity of commercial nonstructural protein 1 (NS1) testing kits for Dengue fever diagnose, and provide the evidence for diagnostic criteria revision. Methods: 300 PCR or virus isolation positive blood samples for dengue virus were collected from sentinel hospitals for dengue surveillance in Guangzhou, Dongguang and Zhongshang from May 2015 to Nov. 2016. At the same time, 308 PCR negative samples for Dengue virus were collected as control group. The information of the sample was collected using questionnaires...
February 6, 2018: Zhonghua Yu Fang Yi Xue za Zhi [Chinese Journal of Preventive Medicine]
Farhana Abu Bakar, Lisa F P Ng
Alphaviruses are enveloped, positive single-stranded RNA viruses, typically transmitted by arthropods. They often cause arthralgia or encephalitic diseases in infected humans and there is currently no targeted antiviral treatment available. The re-emergence of alphaviruses in Asia, Europe, and the Americas over the last decade, including chikungunya and o'nyong'nyong viruses, have intensified the search for selective inhibitors. In this review, we highlight key molecular determinants within the alphavirus replication complex that have been identified as viral targets, focusing on their structure and functionality in viral dissemination...
February 9, 2018: Viruses
Célia Boukadida, Matthieu Fritz, Brigitte Blumen, Marie-Laure Fogeron, François Penin, Annette Martin
Over the recent years, several homologues with varying degrees of genetic relatedness to hepatitis C virus (HCV) have been identified in a wide range of mammalian species. HCV infectious life cycle relies on a first critical proteolytic event of its single polyprotein, which is carried out by nonstructural protein 2 (NS2) and allows replicase assembly and genome replication. In this study, we characterized and evaluated the conservation of the proteolytic mode of action and regulatory mechanisms of NS2 across HCV and animal hepaciviruses...
February 2018: PLoS Pathogens
Lei Xu, Lei Zhou, Weifeng Sun, Pingping Zhang, Xinna Ge, Xin Guo, Jun Han, Hanchun Yang
The highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) has caused huge economic losses to the swine industry in China. Understanding the molecular basis in relation to the virulence of HP-PRRSV is essential for effectively controlling clinical infection and disease. In the current study, we constructed and rescued a serial of mutant viruses in nsp9 and nsp10 based on the differential amino acid sites between HP-PRRSV JXwn06 and LP-PRRSV HB-1/3.9. The replication efficiency in pulmonary alveolar macrophages (PAMs) and the pathogenicity of the mutant viruses for piglets were analyzed...
January 31, 2018: Virology
Xuelian Sui, Xiaojuan Liu, Wenwu Lin, Zujian Wu, Liang Yang
The nonstructural protein pc6 encoded by rice grassy stunt virus (RGSV) plays a significant role in viral cell-to-cell movement, presumably by transport through plasmodesmata (PD). We confirmed the association of pc6 with PD, and also elucidated the mechanisms of protein targeting to PD. Several inhibitor treatments showed conclusively that pc6 is targeted to PD via the ER-to-Golgi secretory system and actin filaments. In addition, VIII-1 myosin was also found to be involved in pc6 PD targeting. Deletion mutants demonstrated that C-terminal amino acid residues 209-229 (transmembrane domain 2; TM2) are essential for pc6 to move through PD...
February 1, 2018: Archives of Virology
Liang Guo, Suresh D Sharma, Jose Debes, Daniel Beisang, Bernd Rattenbacher, Irina Vlasova-St Louis, Darin L Wiesner, Craig E Cameron, Paul R Bohjanen
Numerous mammalian proto-oncogene and other growth-regulatory transcripts are upregulated in malignancy due to abnormal mRNA stabilization. In hepatoma cells expressing a hepatitis C virus (HCV) subgenomic replicon, we found that the viral nonstructural protein 5A (NS5A), a protein known to bind to viral RNA, also bound specifically to human cellular transcripts that encode regulators of cell growth and apoptosis, and this binding correlated with transcript stabilization. An important subset of human NS5A-target transcripts contained GU-rich elements, sequences known to destabilize mRNA...
January 29, 2018: Nucleic Acids Research
Carolin Klemm, Yvonne Boergeling, Stephan Ludwig, Christina Ehrhardt
Influenza epidemics and pandemics still represent a severe public health threat and cause significant morbidity and mortality worldwide. As intracellular parasites, influenza viruses are strongly dependent on the host cell machinery. To ensure efficient production of progeny viruses, viral proteins extensively interfere with cellular signalling pathways to inhibit antiviral responses or to activate virus-supportive functions. Here, we review various functions of the influenza virus nonstructural proteins NS1, PB1-F2, and PA-X in infected cells and how post-transcriptional modifications of these proteins affect the viral life cycle...
January 17, 2018: Trends in Microbiology
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