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https://www.readbyqxmd.com/read/28346435/aav9-mediated-engineering-of-autotransplanted-kidney-of-non-human-primates
#1
S Tomasoni, P Trionfini, N Azzollini, L Zentilin, M Giacca, S Aiello, L Longaretti, E Cozzi, N Baldan, G Remuzzi, A Benigni
Ex vivo gene transfer to the graft before transplantation is an attractive option for circumventing systemic side effects of chronic anti-rejection therapy. Gene delivery of the immunomodulatory protein CTLA4-Ig prevented chronic kidney rejection in a rat model of allotransplantation without the need for systemic immunosuppression. Here, we generated AAV2 and AAV9 vectors encoding for LEA29Y, an optimized version of CTLA4-Ig. Both LEA29Y vectors were equally efficient for reducing T-cell proliferation in vitro...
March 27, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28346434/optimization-of-adeno-associated-virus-vector-mediated-gene-transfer-to-the-respiratory-tract
#2
F Kurosaki, R Uchibori, N Mato, Y Sehara, Y Saga, M Urabe, H Mizukami, Y Sugiyama, A Kume
An efficient adeno-associated virus (AAV) vector was constructed for the treatment of respiratory diseases. AAV serotypes, promoters, and routes of administration potentially influencing the efficiency of gene transfer to airway cells were examined in the present study. Among the nine AAV serotypes (AAV1-9) screened in vitro and four serotypes (AAV1, 2, 6, 9) evaluated in vivo, AAV6 showed the strongest transgene expression. As for promoters, the cytomegalovirus (CMV) early enhancer/chicken β-actin (CAG) promoter resulted in more robust transduction than the CMV promoter...
March 27, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28345672/cyclophilins-and-nucleoporins-are-required-for-infection-mediated-by-capsids-from-circulating-hiv-2-primary-isolates
#3
João I Mamede, Florence Damond, Ariel de Bernardo, Sophie Matheron, Diane Descamps, Jean-Luc Battini, Marc Sitbon, Valérie Courgnaud
HIV-2 groups have emerged from sooty mangabey SIV and entered the human population in Africa on several separate occasions. Compared to world pandemic HIV-1 that arose from the chimpanzee SIVcpz virus, the SIVsm-derived HIV-2, largely confined to West Africa, is less replicative, less transmissible and less pathogenic. Here, we evaluated the interactions between host cellular factors, which control HIV-1 infection and target the capsid, and HIV-2 capsids obtained from primary isolates from patients with different disease progression status...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28345428/induction-of-t-cell-infiltration-and-programmed-death-ligand-2-expression-by-adeno-associated-virus-in-rhesus-macaque-skeletal-muscle-and-modulation-by-prednisone
#4
Megan L Cramer, Guohong Shao, Louise R Rodino-Klapac, Louis G Chicoine, Paul T Martin
Use of adeno-associated virus (AAV) to transduce genes into skeletal muscles can be associated with T-cell responses to viral capsid and/or to transgenic protein. Intramuscular mononuclear cell infiltrates primarily consisting of CD8+ T cells and also containing FOXP3+ regulatory T cells were present in rhesus macaque skeletal muscle treated with rAAVrh74.MCK.GALGT2 by vascular delivery. Administration of oral prednisone prior to AAV gene delivery and throughout the study reduced such infiltrates by 60% at 24 weeks post-AAV delivery compared to AAV-treated animals not receiving prednisone, regardless of the presence of pre-existing AAV serum antibodies at the time of treatment...
March 27, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28345000/syngeneic-aav-pseudo-particles-potentiate-gene-transduction-of-aav-vectors
#5
Qizhao Wang, Biao Dong, Katie A Pokiniewski, Jenni Firrman, Zhongren Wu, Mario P S Chin, Xiongwen Chen, LinShu Liu, Ruian Xu, Yong Diao, Weidong Xiao
Adeno-associated virus (AAV) vectors have emerged as a safe and efficient gene therapy platform. One complication is that a significant amount of empty particles have always been generated as impurities during AAV vector production. However, the effects of such particles on AAV vector performance remain unclear. Here we systemically evaluated the biological properties of three types of "empty" AAV particles: syngeneic pseudo-vectors with partial AAV genomes derived from DNA of the corresponding full particles, allogeneic pseudo-vectors with partial genomes different from the corresponding full particles, and null pseudo-vectors with no DNA inside the capsids...
March 17, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28344872/intravenously-usable-fully-serotype-3-oncolytic-adenovirus-coding-for-cd40l-as-an-enabler-of-dendritic-cell-therapy
#6
Sadia Zafar, Suvi Parviainen, Mikko Siurala, Otto Hemminki, Riikka Havunen, Siri Tähtinen, Simona Bramante, Lotta Vassilev, Hongjie Wang, Andre Lieber, Silvio Hemmi, Tanja de Gruijl, Anna Kanerva, Akseli Hemminki
Vaccination with dendritic cells (DCs), the most potent professional antigen-presenting cells in the body, is a promising approach in cancer immunotherapy. However, tumors induce immunosuppression in their microenvironment that suppresses and impairs the function of DCs. Therefore, human clinical trials with DC therapy have often been disappointing. To improve the therapeutic efficacy and to overcome the major obstacles of DC therapy, we generated a novel adenovirus, Ad3-hTERT-CMV-hCD40L, which is fully serotype 3 and expresses hCD40L for induction of antitumor immune response...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344575/identification-of-capsid-coat-related-protein-folds-and-their-utility-for-virus-classification
#7
Arshan Nasir, Gustavo Caetano-Anollés
The viral supergroup includes the entire collection of known and unknown viruses that roam our planet and infect life forms. The supergroup is remarkably diverse both in its genetics and morphology and has historically remained difficult to study and classify. The accumulation of protein structure data in the past few years now provides an excellent opportunity to re-examine the classification and evolution of viruses. Here we scan completely sequenced viral proteomes from all genome types and identify protein folds involved in the formation of viral capsids and virion architectures...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28344351/viral-evolution-on-the-origin-of-capsids
#8
Ashley York
No abstract text is available yet for this article.
March 27, 2017: Nature Reviews. Microbiology
https://www.readbyqxmd.com/read/28342032/densoviruses-in-oyster-crassostrea-ariakensis
#9
Yan-Jun Kang, Wei Huang, A-Li Zhao, Dan-Dan Lai, Lin Shao, Yan-Qin Shen, Xutao Deng, Eric Delwart, Wen Zhang
Densoviruses have short ssDNA genomes and mainly infect arthropods. To characterize viral nucleic acid in shellfish, oysters (Crassostrea ariakensis) were analyzed using viral metagenomics. Two large de novo assembled contigs, CaaDV1 and CaaDV2, consisting of nearly complete densovirus genomes (5860 nucleotides (nt) and 4034 nt) with two major ambisense protein coding regions were identified. Several potential non-structural proteins and capsid proteins were encoded by these genomes, but these were divergent from the existing densoviral species...
March 24, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28339215/discovery-and-pre-clinical-characterization-of-a-3-rd-generation-4-h-heteroaryldihydropyrimidine-hap-analogues-as-hepatitis-b-virus-hbv-capsid-inhibitors
#10
Zongxing Qiu, Xianfeng Lin, Weixing Zhang, Mingwei Zhou, Lei Guo, Buelent Kocer, Guolong Wu, Zhisen Zhang, Haixia Liu, Houguang Shi, Buyu Kou, Taishan Hu, Yimin Hu, Mengwei Huang, S Frank Yan, Zhiheng Xu, Zheng Zhou, Ning Qin, Yue Fen Wang, Shuang Ren, Hongxia Qiu, Yuxia Zhang, Yi Zhang, Xiaoyue Wu, Kai Sun, Sheng Zhong, Jianxun Xie, Giorgio Ottaviani, Yuan Zhou, Lina Zhu, Xiaojun Tian, Liping Shi, Fang Shen, Yi Mao, Xue Zhou, Lu Gao, John A T Young, Jim Zhen Wu, Guang Yang, Alexander V Mayweg, Hong C Shen, Guozhi Tang, Wei Zhu
Described herein are the discovery and structure-activity relationship (SAR) studies of the 3(rd) generation 4-H heteroaryldihydropyrimidines (4-H HAPs) featuring the introduction of a C6 carboxyl group as novel HBV capsid inhibitors. This new series of 4-H HAPs showed improved anti-HBV activity and better drug-like properties compared to the 1(st) and 2(nd) generation 4-H HAPs. X-ray crystallographic study of analogue 12 (HAP_R01) with Cp149 Y132A mutant hexamer clearly elucidated the role of C6 carboxyl group played for the increased binding affinity, which formed strong hydrogen bonding interactions with capsid protein and coordinated waters...
March 24, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28335554/complete-and-incomplete-hepatitis-b-virus-particles-formation-function-and-application
#11
REVIEW
Jianming Hu, Kuancheng Liu
Hepatitis B virus (HBV) is a para-retrovirus or retroid virus that contains a double-stranded DNA genome and replicates this DNA via reverse transcription of a RNA pregenome. Viral reverse transcription takes place within a capsid upon packaging of the RNA and the viral reverse transcriptase. A major characteristic of HBV replication is the selection of capsids containing the double-stranded DNA, but not those containing the RNA or the single-stranded DNA replication intermediate, for envelopment during virion secretion...
March 21, 2017: Viruses
https://www.readbyqxmd.com/read/28335455/viral-protein-kinetics-of-piscine-orthoreovirus-infection-in-atlantic-salmon-blood-cells
#12
Hanne Merethe Haatveit, Øystein Wessel, Turhan Markussen, Morten Lund, Bernd Thiede, Ingvild Berg Nyman, Stine Braaen, Maria Krudtaa Dahle, Espen Rimstad
Piscine orthoreovirus (PRV) is ubiquitous in farmed Atlantic salmon (Salmo salar) and the cause of heart and skeletal muscle inflammation. Erythrocytes are important target cells for PRV. We have investigated the kinetics of PRV infection in salmon blood cells. The findings indicate that PRV causes an acute infection of blood cells lasting 1-2 weeks, before it subsides into persistence. A high production of viral proteins occurred initially in the acute phase which significantly correlated with antiviral gene transcription...
March 18, 2017: Viruses
https://www.readbyqxmd.com/read/28334092/the-cuticle-protein-gene-mpcp4-of-myzus-persicae-homoptera-aphididae-plays-a-critical-role-in-cucumber-mosaic-virus-acquisition
#13
Yan Liang, Xi-Wu Gao
Myzus persicae (Sulzer) (Homoptera: Aphididae) is one of the most important agricultural pests worldwide. In addition to sucking phloem sap, M. persicae also transmits Cucumber mosaic virus (CMV) as a vector in a nonpersistent manner. At present, the infection mechanism remains unclear, especially the process of aphid virus acquisition. In this study, we isolated four M. persicae cuticle protein genes (MPCP1, MPCP2, MPCP4, and MPCP5) from M. persicae. The relative amount of the gene encoding Cucumber mosaic virus capsid protein (CMV CP) and the transcript levels of these four cuticle protein genes were investigated in aphid virus acquisition by feeding the tobacco preinfested by CMV...
February 19, 2017: Journal of Economic Entomology
https://www.readbyqxmd.com/read/28332826/packaged-and-free-stmv-rna-genomes-adopt-distinct-conformational-states
#14
Bridget C Larman, Elizabeth A Dethoff, Kevin M Weeks
The RNA genomes of viruses likely undergo multiple functionally important conformational changes during their replication cycles, changes that are poorly understood at present. We used two complementary in-solution RNA structure probing strategies (SHAPE-MaP and RING-MaP) to examine the structure of the RNA genome of satellite tobacco mosaic virus inside authentic virions and in a capsid-free state. Both RNA states feature similar three-domain architectures in which each major replicative function - translation, capsid coding, and genome synthesis - fall into distinct domains...
March 23, 2017: Biochemistry
https://www.readbyqxmd.com/read/28331984/structure-of-the-n-glycans-from-the-chlorovirus-ne-jv-1
#15
Immacolata Speciale, Irina Agarkova, Garry A Duncan, James L Van Etten, Cristina De Castro
Results from recent studies are breaking the paradigm that all viruses depend on their host machinery to glycosylate their proteins. Chloroviruses encode several genes involved in glycan biosynthesis and some of their capsid proteins are decorated with N-linked oligosaccharides with unique features. Here we describe the elucidation of the N-glycan structure of an unusual chlorovirus, NE-JV-1, that belongs to the Pbi group. The host for NE-JV-1 is the zoochlorella Micractinium conductrix. Spectroscopic analyses established that this N-glycan consists of a core region that is conserved in all of the chloroviruses...
March 22, 2017: Antonie Van Leeuwenhoek
https://www.readbyqxmd.com/read/28331094/herpes-simplex-virus-ge-gi-and-us9-promote-both-envelopment-and-sorting-of-virus-particles-in-the-cytoplasm-of-neurons-two-processes-that-precede-anterograde-transport-in-axons
#16
Grayson DuRaine, Todd W Wisner, Paul Howard, David C Johnson
Herpes simplex virus (HSV) anterograde transport in neuronal axons is vital, allowing spread from latently-infected ganglia to epithelial tissues where viral progeny are produced in numbers allowing spread to other hosts. HSV membrane proteins gE/gI and US9 initiate the process of anterograde axonal transport ensuring that virus particles are transported from the cytoplasm into the most proximal segments of axons. These proteins do not appear to be important once HSV is inside axons. Previously we described HSV double mutants lacking both gE and US9 that failed to transport virus particles into axons...
March 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28331093/structural-characterization-of-hcov-nl63-n-protein
#17
Bozena Szelazek, Wojciech Kabala, Krzysztof Kus, Michal Zdzalik, Aleksandra Twarda-Clapa, Przemyslaw Golik, Michal Burmistrz, Dominik Florek, Benedykt Wladyka, Krzysztof Pyrc, Grzegorz Dubin
Coronaviruses are responsible for upper and lower respiratory tract infections in humans. It is estimated that 1-10% of the population suffers annually from cold-like symptoms related to infection with HCoV-NL63, an alphacoronavirus. The nucleocapsid (N) protein, the major structural component of the capsid, facilitates RNA packing, links the capsid to the envelope and is also involved in multiple other processes including viral replication and evasion of the immune system. Although the role of N protein in viral replication is relatively well described, no structural data are currently available regarding the N proteins of alphacoronaviruses...
March 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28331084/structural-insights-into-emerging-pediatric-pathogens-human-bocaparvoviruses
#18
Mario Mietzsch, Shweta Kailasan, Jamie Garrison, Maria Ilyas, Paul Chipman, Kalle Kantola, Mandy E Janssen, John Spear, Duncan Sousa, Robert McKenna, Kevin Brown, Maria Söderlund-Venermo, Timothy Baker, Mavis Agbandje-McKenna
Bocaparvoviruses are emerging pathogens of the Parvoviridae family. Human bocaviruses 1 (HBoV1) causes severe respiratory infections and HBoV2-4 gastrointestinal infections in young children. Recent reports of life threatening cases, lack of direct treatment or vaccination, and a limited understanding of their disease mechanisms demand the need to study these pathogens on a molecular and structural level for the development of therapeutics. Towards this end, the capsid structures of HBoV1, HBoV3, and HBoV4 were determined to 2...
March 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28330110/sequence-based-approach-for-rapid-identification-of-cross-clade-cd8-t-cell-vaccine-candidates-from-all-high-risk-hpv-strains
#19
Krishna P Singh, Neeraj Verma, Bashir A Akhoon, Vishal Bhatt, Shishir K Gupta, Shailendra K Gupta, Suchi Smita
Human papilloma virus (HPV) is the primary etiological agent responsible for cervical cancer in women. Although in total 16 high-risk HPV strains have been identified so far. Currently available commercial vaccines are designed by targeting mainly HPV16 and HPV18 viral strains as these are the most common strains associated with cervical cancer. Because of the high level of antigenic specificity of HPV capsid antigens, the currently available vaccines are not suitable to provide cross-protection from all other high-risk HPV strains...
June 2016: 3 Biotech
https://www.readbyqxmd.com/read/28329017/navigating-in-foldonia-using-accelerated-molecular-dynamics-to-explore-stability-unfolding-and-self-healing-of-the-%C3%AE-solenoid-structure-formed-by-a-silk-like-polypeptide
#20
Binwu Zhao, Martien A Cohen Stuart, Carol K Hall
The β roll molecules with sequence (GAGAGAGQ)10 stack via hydrogen bonding to form fibrils which have been themselves been used to make viral capsids of DNA strands, supramolecular nanotapes and pH-responsive gels. Accelerated molecular dynamics (aMD) simulations are used to investigate the unfolding of a stack of two β roll molecules, (GAGAGAGQ)10, to shed light on the folding mechanism by which silk-inspired polypeptides form fibrils and to identify the dominant forces that keep the silk-inspired polypeptide in a β roll configuration...
March 22, 2017: PLoS Computational Biology
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