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Efficient HIV-1 in vitro reverse transcription: optimal capsid stability is required

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Signal Transduction and Targeted Therapy 2021年第2期6卷 195-196页

作者： Ryan C.Burdick Vinay K.Pathak viral mutation section HIV Dynamics and Replication ProgramCenter for Cancer ResearchNational Cancer Institute at FrederickFrederickMD 21702USA

Recently,Christensen et *** HIV-1 reverse transcription and integration in a cell-free system and found that viral double-stranded DNA that is capable of integration into a target plasmid DNA was efficiently synthesized within viral cores,indicating that the capsid protein shell plays an important role in viral genome replication.1 HIV-1 reverse transcriptase(RT)copies the viral genomic RNA into a double-stranded DNA,and HIV-1 integrase(IN)inserts the viral DNA into the host genome to form a *** RT and IN have been successfully targeted with potent antiretroviral drugs to inhibit these enzymes and treat patients infected with HIV-1,the causative agent of acquired immunodeficiency syndrome(AIDS).Despite decades of research,the molecular mechanisms of reverse transcription and integration in vivo are not fully characterized,in part because cell-free assays that efficiently and faithfully recapitulate the processes in the context of a virion have not been available。

关键词： al. drugs optimal

To Analyze the Sensitivity of RT-PCR Assays Employing S Gene Target Failure with Whole Genome Sequencing Data during Third Wave by SARS-CoV-2 Omicron Variant

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Advances in Microbiology 2024年第5期14卷 247-255页

作者： Pooja Patel Yogita Mistry Monika Patel Summaiya Mullan viral Research and Diagnostic Laboratory Department of Microbiology Government Medical college Surat India

Introduction: Omicron is a highly divergent variant of concern (VOCs) of a severe acute respiratory syndrome SARS-CoV-2. It carries a high number of mutations in its spike protein hence;it is more transmissible in the community by immune evasion mechanisms. Due to mutation within S gene, most Omicron variants have reported S gene target failure (SGTF) with some commercially available PCR kits. Such diagnostic features can be used as markers to screen Omicron. However, Whole Genome Sequencing (WGS) is the only gold standard approach to confirm novel microorganisms at genetically level as similar mutations can also be found in other variants that are circulating at low frequencies worldwide. This Retrospective study is aimed to assess RT-PCR sensitivity in the detection of S gene target failure in comparison with whole genome sequencing to detect variants of Omicron. Methods: We have analysed retrospective data of SARS-CoV-2 positive RT-PCR samples for S gene target failure (SGTF) with TaqPath COVID-19 RT-PCR Combo Kit (ThermoFisher) and combined with sequencing technologies to study the emerged pattern of SARS-CoV-2 variants during third wave at the tertiary care centre, Surat. Results: From the first day of December 2021 till the end of February 2022, a total of 321,803 diagnostic RT-PCR tests for SARS-CoV-2 were performed, of which 20,566 positive cases were reported at our tertiary care centre with an average cumulative positivity of 6.39% over a period of three months. In the month of December 21 samples characterized by the SGTF (70/129) were suggestive of being infected by the Omicron variant and identified as Omicron (B.1.1.529 lineage) when sequence. In the month of January, we analysed a subset of samples (n = 618) with SGTF (24%) and without SGTF (76%) with Ct values Conclusions: During the COVID-19 pandemic, it took almost more than 15 days to diagnose infection and identify pathogen by sequencing technology. In contrast to that molecular assay provided qu

关键词： SARS-CoV-2 S Gene Target Failure Whole Genome Sequencing Omicron

Calmodulin-like 5 promotes PEDV replication by regulating late-endosome synthesis and innate immune response

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Virologica Sinica 2024年第3期39卷 501-512页

作者： Wen-Jun Tian Xiu-Zhong Zhang Jing Wang Jian-Feng Liu Fu-Huang Li Xiao-Jia Wang National Key Laboratory of Veterinary Public Health and Safety College of Veterinary MedicineChina Agricultural UniversityBeijing 100193China College of Animal Science and Technology China Agricultural UniversityBeijing 100193China Beijing General Station of Animal Husbandry Service(South section) Beijing102218China

The infection caused by porcine epidemic diarrhea virus(PEDV)is associated with high mortality in piglets *** factors involved in the efficient replication of PEDV,however,remain largely *** recent proteomic study in the virus-host interaction network revealed a significant increase in the accumulation of CALML5(EF-hand protein calmodulin-like 5)following PEDV infection.A further study unveiled a biphasic increase of CALML5 in 2 and 12 h after viral *** trends were observed in the intestines of piglets in the early and late stages of the PEDV ***,CALML5 depletion reduced PEDV mRNA and protein levels,leading to a one-order-of-magnitude decrease in virus *** the early stage of PEDV infection,CALML5 affected the endosomal trafficking pathway by regulating the expression of endosomal sorting complex related cellular ***5 depletion also suppressed IFN-βand IL-6 production in the PEDV-infected cells,thereby indicating its involvement in negatively regulating the innate immune *** study reveals the biological function of CALML5 in the virology field and offers new insights into the PEDV-host cell interaction.

关键词： Porcine epidemic diarrhea virus(PEDV) EF-hand protein calmodulin-like 5(CALML5) Late endosomes Innate immune response

Flu DRiPs in MHC Class Ⅰ Immunosurveillance

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Virologica Sinica 2019年第2期34卷 162-167页

作者： Jiajie Wei Jonathan W.Yewdell Cellular Biology section Laboratory of Viral DiseasesNational Institute of Allergy and Infectious DiseasesNational Institutes of Health

Since the publication of the DRiP(defective ribosomal product) hypothesis in 1996, numerous studies have addressed the contribution of DRiPs to generating viral antigenic peptides for CD8^+T cell immunosurveillance. Here, we review studies characterizing the generation of antigenic peptides from influenza A virus encoded DRiPs, discuss the many remaining mysteries regarding the nature of their co-translational generation, and speculate on where the future might lead.

关键词： Influenza A virus(IAV) MHC-restricted cytotoxicity Immune responses MHC class Ⅰ DRiP

Split intein-mediated protein trans-splicing to express large dystrophins

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四川生理科学杂志 2024年第7期46卷 1627-1627页

作者： Hichem Tasfaout Department of Neurology University of Washington School of Medicine Seattle WA USA Senator Paul D. Wellstone Muscular Dystrophy Specialized Research Center University of Washington School of Medicine Seattle WA USA Department of Biochemistry University of Washington School of Medicine Seattle WA USA Center for Translational Muscle Research University of Washington Seattle WA USA Department of Bioengineering College of Engineering and School of Medicine University of Washington Seattle WA USA Department of Infectious Diseases/Virology Section Viral Vector Technologies Medical Faculty and Faculty of Engineering Sciences Center for Integrative Infectious Disease Research (CIID) University of Heidelberg Heidelberg Germany BioQuant University of Heidelberg Heidelberg Germany German Center for Infection Research (DZIF) and German Center for Cardiovascular Research (DZHK) Heidelberg Germany

Gene replacement using adeno-associated virus(AAV)vectors is a promising therapeutic approach for many diseases1,***,this therapeutic modality is challenged by the packaging capacity of AAVs(approximately 4.7 kilobases)3,limiting its application for disorders involving large coding sequences,such as Duchenne muscular dystrophy,with a 14 kilobase messenger RNA.

关键词： Split bases limiting

Autosomal dominant polycystic liver disease in a family without polycystic kidney disease associated with a novel missense protein kinase C substrate 80K-H mutation

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World Journal of Gastroenterology 2005年第48期11卷 7690-7693页

作者： Ramón Peces Joost PH Drenth Rene HM te Morsche Pedro González Carlos Peces section of Nephrology Department of Medicine section of Digestive Hospital General La Mancha-Centro Computer Science Superior School

Polycystic liver disease (PLD) is characterized by the presence of multiple bile duct-derived epithelial cysts scattered in the liver parenchyma. PLD can manifest itself in patients with severe autosomal dominant polycystic kidney disease (ADPKD). Isolated autosomal dominant polycystic liver disease (ADPLD) is genetically distinct from PLD associated with ADPKD, although it may have similar pathogenesis and clinical ***, mutations in two causative genes for ADPLD,independently from ADPKD, have been identified. We report here a family (a mother and her daughter) with a severe form of ADPLD not associated with ADPKD produced by a novel missense protein kinase C substrate 80K-H (PRKCSH) mutation (R281W). This mutation causes a severe phenotype, since the two affected subjects manifested signs of portal hypertension. Doppler sonography, computed tomography (CT) and magnetic resonance (MR) imaging are effective in documenting the underlying lesions in a non-invasive way.

关键词： ADPLD Hepatic cysts Hepatocystin Inferior vena cava compression Polycystic liver disease Portal hypertension

Clinical and molecular characterization of 10 Chinese children with congenital adrenal hyperplasia due to 11beta‑hydroxylase deficiency

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World Journal of Pediatrics 2024年第4期20卷 422-433页

作者： Wen‑Li Lu Xiao‑Yu Ma Jiao Zhang Jun‑Qi Wang Ting‑Ting Zhang Lei Ye Yuan Xiao Zhi‑Ya Dong Wei Wang Shou‑Yue Sun Chuan‑Yin Li Rong‑Gui Hu Guang Ning Li‑Dan Zhang Department of Pediatrics Ruijin HospitalShanghai Jiao Tong University School of MedicineNo.197Ruijin 2nd RdHuangpu DistrictShanghai 200025China Department of Pediatric Genetic and Metabolic Endocrinology West China Second University HospitalSichuan UniversityNo.20Section 3Renmin South RoadSichuan 610041China Department of Endocrine and Metabolic Diseases Shanghai Clinical Center for Endocrine and Metabolic DiseasesRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China Cancer Center School of MedicineShanghai Tenth People’s HospitalTongji UniversityYanchang Zhong Lu 301St RdJing’an DistrictShanghai 200031China

Background The clinical manifestations of nonclassical 11beta-hydroxylase deficiency are very similar to those of nonclassical 21-hydroxylase *** this study,we investigated the relationship between the clinical and molecular features of congenital adrenal hyperplasia caused by 11beta-hydroxylase deficiency and reviewed the related literature,which are expected to provide assistance for the clinical diagnosis and analysis of congenital adrenal *** Clinical data for 10 Chinese patients diagnosed with congenital adrenal hyperplasia in our hospital from 2018 to 2022 were retrospectively *** examined the effects of gene mutations on protease activity and constructed threedimensional structure prediction models of *** We describe 10 patients with 11beta-hydroxylase gene mutations(n=5,46,XY;n=5,46,XX),with 10 novel mutations were *** patients received treatment at an early stage,with an average age of 2.08±1.66 years,whereas male patients received treatment significantly later,at an average age of 9.77±3.62 *** most common CYP11B1 pathogenic variant in the Chinese population was found to be c.1360C>*** mutations lead to spatial conformational changes that affect protein *** Our study found that there was no significant correlation between each specific mutation and the severity of clinical *** patients with the same gene pathogenic variant may have mild or severe clinical *** correlation between genotype and phenotype needs further ***-dimensional protein simulations may provide additional support for the physiopathological mechanism of genetic mutations.

关键词： 11β-hydroxylase deficiency CYP11B1 Enzymatic activity Phenotype-genotype correlation Threedimensional protein simulations

Driving forces of continuing evolution of rotaviruses

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World Journal of Virology 2024年第2期13卷 58-70页

作者： Mohamad Saifudin Hakim Faris Muhammad Gazali Suci Ardini Widyaningsih Mohammad Khalid Parvez Postgraduate School of Molecular Medicine Erasmus MC-University Medical CenterRotterdam 3015GDNetherlands viral Infection Working Group International Society of Antimicrobial ChemotherapyLondon EC4R 9ANUnited Kingdom Master Program in Biotechnology Postgraduate SchoolUniversitas Gadjah MadaYogyakarta55281Indonesia Master of Medical Sciences in Clinical Investigation Harvard Medical SchoolBostonMA 02115United States Department of Pharmacognosy College of PharmacyKing Saud UniversityRiyadh11451Saudi Arabia

Rotaviruses are non-enveloped double-stranded RNA virus that causes acute diarrheal diseases in children(<5 years).More than 90%of the global rotavirus infection in humans was caused by Rotavirus group *** infection h... 详细信息

Rotaviruses are non-enveloped double-stranded RNA virus that causes acute diarrheal diseases in children(mutation rate,glycan specificity,vaccine introduction,the host immune respo-nses,and antiviral drugs.

关键词： Rotavirus Epidemiology Evolution Reassortment Vaccine

Assembly and release of infectious hepatitis C virus involving unusual organization of the secretory pathway

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World Journal of Hepatology 2016年第19期8卷 796-814页

作者： Miriam Triyatni Edward A Berger Bertrand Saunier Roche Innovation Center Roche Pharma Research and Early Development F. Hoffmann-La Roche Ltd. Molecular Structure section Laboratory of Viral Diseases NIAID NIH Unité de Virologie Structurale Institut Pasteur and CNRS UMR 3569

AIM: To determine if calnexin(CANX), RAB1 and alphatubulin were involved in the production of hepatitis C virus(HCV) particles by baby hamster kidney-West Nile virus(BHK-WNV) cells. METHODS: Using a si RNA-based approach complemented with immuno-fluorescence confocal microscope and Western blot studies, we examined the roles of CANX, RAB1 and alpha-tubulin in the production of HCV particles by permissive BHK-WNV cells expressing HCV structural proteins or the full-length genome of HCV genotype 1a. Immuno-fluorescence studies in producer cells were performed with monoclonal antibodies against HCV structural proteins, as well as immunoglobulin from the serum of a patient recently cured from an HCV infection of same genotype. The cellular compartment stained by the serum immunoglobulin was also observedin thin section transmission electron microscopy. These findings were compared with the JFH-1 strain/Huh-7.5 cell ***: We found that CANX was necessary for the production of HCV particles by BHK-WNV cells. This process involved the recruitment of a subset of HCV proteins, detected by immunoglobulin of an HCV-cured patient, in a compartment of rearranged membranes bypassing the endoplasmic reticulum-Golgi intermediary compartment and surrounded by mitochondria. It also involved the maturation of N-linked glycans on HCV envelope proteins, which was required for assembly and/or secretion of HCV particles. The formation of this specialized compartment required RAB1; upon expression of HCV structural genes, this compartment developed large vesicles with viral particles. RAB1 and alpha-tubulin were required for the release of HCV particles. These cellular factors were also involved in the production of HCVcc in the JFH-1 strain/Huh-7.5 cell system, which involves HCV RNA replication. The secretion of HCV particles by BHK-WNV cells presents similarities with a pathway involving caspase-1; a caspase-1 inhibitor was found to suppress the production of HCV particles from

关键词： Membrane rearrangements Hepatitis C virus Flavivirus replicon Virus assembly and secretion Host cellular factors