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Annebel R De Vleeschauwer, Xiaocui Zhou, David J Lefebvre, Annabelle Garnier, Fleur Watier, Charly Pignon, Sandrine A Lacour, Stephan Zientara, Labib Bakkali-Kassimi, Kris De Clercq, Bernard Klonjkowski
Vaccination is a key element in the control of foot-and-mouth disease (FMD). The majority of the antigenic sites that induce protective immune responses are localized on the FMD virus (FMDV) capsid that is formed by four virus-encoded structural proteins, VP1 to VP4. In the present study, recombinant canine adenovirus type 2 (CAV2)-based FMD vaccines, Cav-P1/3C R° and Cav-VP1 R°, respectively expressing the structural P1 precursor protein along with the non-structural 3C protein or expressing the structural VP1 protein of the FMDV strain O/FRA/1/2001, were evaluated as novel vaccines against FMD...
March 12, 2018: Vaccine
Minghua Zheng, Jie Jiang, Xiao Zhang, Nan Wang, Kaihang Wang, Qiong Li, Tingting Li, Qingshan Lin, Yingbin Wang, Hai Yu, Ying Gu, Jun Zhang, Shaowei Li, Ningshao Xia
Hepatitis E virus (HEV) is associated with acute hepatitis disease. Numerous truncated HEV capsid proteins have been successfully expressed using different expression systems. Among these, p495, a protein truncated at its N- and C-termini by 111 and 54 amino acids (aa), respectively (HEV ORF2 aa 112-606) can self-assemble into T = 1 virus-like particles (VLPs) when expressed by insect cells. A shorter p239 (aa 368-606) protein is a particulate antigen that we have previously used in our commercialized HEV vaccine, Hecolin...
March 12, 2018: Vaccine
Amit Gaba, Lisanework E Ayalew, Amrutlal Patel, Pankaj Kumar, Suresh K Tikoo
Adenovirus protein VIII appears to connect core with the inner surface of the adenovirus capsid. Since protein- protein interactions are central to virus replication, identification of proteins interacting with protein VIII may help in understanding their role in adenovirus infection. Our yeast two hybrid assay indicated that protein VIII interacts with eukaryotic initiation factor 6 (eIF6). These findings were confirmed by GST-pull down assay, bimolecular fluorescent complementation assay and co-immunoprecipitation assay in plasmid DNA transfected and BAdV-3 infected cells...
March 15, 2018: Cellular Microbiology
Lauriane Lecoq, Shishan Wang, Thomas Wiegand, Stéphane Bressanelli, Michael Nassal, Beat H Meier, Anja Böckmann
The hepatitis B virus (HBV) icosahedral nucleocapsid is assembled from 240 chemically identical core protein molecules and, structurally, comprises four groups of symmetrically nonequivalent subunits. We show here that this asymmetry is reflected in solid-state NMR spectra of the capsids in which peak splitting is observed for a subset of residues. We compare this information to dihedral angle variations from available 3D structures, and also to computational predictions of dynamic domains and molecular hinges...
March 15, 2018: Chemphyschem: a European Journal of Chemical Physics and Physical Chemistry
Katarzyna Brach, Akiko Hatakeyama, Claude Nogues, Joanna Olesiak-Banska, Malcolm Buckle, Katarzyna Matczyszyn
The anisotropic shape of DNA molecules allows them to form lyotropic liquid crystals (LCs) at high concentrations. This liquid crystalline arrangement is also found in vivo (e.g., in bacteriophage capsids, bacteria or human sperm nuclei). However, the role of DNA liquid crystalline organization in living organisms still remains an open question. Here we show that in vitro, the DNA spatial structure is significantly changed in mesophases compared to non-organized DNA molecules. DNA LCs were prepared from pBluescript SK (pBSK) plasmid DNA and investigated by photochemical analysis of structural transitions (PhAST)...
March 14, 2018: Scientific Reports
Xiaoling Wang, Xiuling Cao, Min Liu, Ruiqi Zhang, Xin Zhang, Zongyu Gao, Xiaofei Zhao, Kai Xu, Dawei Li, Yongliang Zhang
Dissecting the complex molecular interplay between the host plant and invading virus improves our understanding of the mechanisms underlying viral pathogenesis. In this study, immunoprecipitation together with the mass spectrometry analysis revealed that the heat shock protein 70 (Hsp70) family homolog, Hsc70-2, was co-purified with beet black scorch virus (BBSV) replication protein p23 and coat protein (CP), respectively. Further experiments demonstrated that Hsc70-2 interacts directly with both p23 and CP, whereas there is no interaction between p23 and CP...
March 14, 2018: Scientific Reports
María Cecilia Gimenez, Flavia Adriana Zanetti, Mauricio R Terebiznik, María Isabel Colombo, Laura Ruth Delgui
Birnaviruses are unconventional members of the double-stranded RNA (dsRNA) viruses group that are characterized by the lack of a transcriptionally active inner core. Instead, the birnaviral particles organize their genome in ribonucleoprotein complexes (RNPs) composed by dsRNA segments, the dsRNA-binding VP3 protein, and the viral encoded RNA-dependent RNA-polymerase (RdRp). This and other structural features suggests that birnaviruses may follow a completely different replication program from that followed by members of the Reoviridae family, supporting the hypothesis that birnaviruses are the evolutionary link between single-stranded positive RNA (+ssRNA) and dsRNA viruses...
March 14, 2018: Journal of Virology
A Esteves, J Nordgren, C Tavares, F Fortes, R Dimbu, N Saraiva, C Istrate
Norovirus (NoV) is a major cause of acute gastroenteritis (AGE). In this study, we investigated the genetic diversity of NoV strains identified in children under 5 years of age with AGE in four provinces of Angola. Faecal samples from 343 children were screened for NoV by an in house real-time PCR assay and genotyping was performed by partial capsid gene sequencing. NoV was detected in 17.4% (58/334) of the samples, with high detection rates in children <6 months old (19%) and in children aged 12-24 months (23%)...
March 14, 2018: Epidemiology and Infection
Raquel T Yokoda, Bolni M Nagalo, Mitesh J Borad
Gastrointestinal malignancies are challenging cancers with considerable economic and societal impacts on health care systems worldwide. While advances in surgical approaches have provided benefits to a proportion of patients, only modest improvements have been attained in the treatment of patients with advanced disease, resulting in limited improvement in survival rates in these patients. Oncolytic adenoviruses are being developed to address gastrointestinal malignancies. Each platform has evolved to maximize tumor-cell killing potency while minimizing toxicities...
March 11, 2018: Biomedicines
Jonathan J Knowlton, Isabel Fernández de Castro, Alison W Ashbrook, Daniel R Gestaut, Paula F Zamora, Joshua A Bauer, J Craig Forrest, Judith Frydman, Cristina Risco, Terence S Dermody
Viruses are molecular machines sustained through a life cycle that requires replication within host cells. Throughout the infectious cycle, viral and cellular components interact to advance the multistep process required to produce progeny virions. Despite progress made in understanding the virus-host protein interactome, much remains to be discovered about the cellular factors that function during infection, especially those operating at terminal steps in replication. In an RNA interference screen, we identified the eukaryotic chaperonin T-complex protein-1 (TCP-1) ring complex (TRiC; also called CCT for chaperonin containing TCP-1) as a cellular factor required for late events in the replication of mammalian reovirus...
March 12, 2018: Nature Microbiology
Bruce L Innis, Julia A Lynch
Soon after the 1991 molecular cloning of hepatitis E virus (HEV), recombinant viral capsid antigens were expressed and tested in nonhuman primates for protection against liver disease and infection. Two genotype 1 subunit vaccine candidates entered clinical development: a 56 kDA vaccine expressed in insect cells and HEV 239 vaccine expressed in Escherichia coli Both were highly protective against hepatitis E and acceptably safe. The HEV 239 vaccine was approved in China in 2011, but it is not yet prequalified by the World Health Organization, a necessary step for introduction into those low- and middle-income countries where the disease burden is highest...
March 12, 2018: Cold Spring Harbor Perspectives in Medicine
Rosa M Pintó, Francisco-Javier Pérez-Rodríguez, Lucia D' Andrea, Montserrat de Castellarnau, Susana Guix, Albert Bosch
Codon usage bias is universal to all genomes. Hepatitis A virus (HAV) codon usage is highly biased and deoptimized with respect to its host. Accordingly, HAV is unable to induce cellular translational shutoff and its internal ribosome entry site (IRES) is inefficient. Codon usage deoptimization may be seen as a hawk (host cell) versus dove (HAV) game strategy for accessing transfer RNA (tRNA). HAV avoids use of abundant host cell codons and thereby eludes competition for the corresponding tRNAs. Instead, codons that are abundant or rare in cellular messenger RNAs (mRNAs) are used relatively rarely in its genome, although intermediately abundant host cell codons are abundant in the viral genome...
March 12, 2018: Cold Spring Harbor Perspectives in Medicine
Scott P Kenney, Xiang-Jin Meng
Hepatitis E virus (HEV) possesses many of the features of other positive-stranded RNA viruses but also adds HEV-specific nuances, making its virus-host interactions unique. Slow virus replication kinetics and fastidious growth conditions, coupled with the historical lack of an efficient cell culture system to propagate the virus, have left many gaps in our understanding of its structure and replication cycle. Recent advances in culturing selected strains of HEV and resolving the 3D structure of the viral capsid are filling in knowledge gaps, but HEV remains an extremely understudied pathogen...
March 12, 2018: Cold Spring Harbor Perspectives in Medicine
Belén Rebollo, Javier Sarraseca, Mª José Rodríguez, Antonio Sanz, Miguel Ángel Jiménez-Clavero, Ángel Venteo
West Nile virus is a globally spread zoonotic arbovirus. The laboratory diagnosis of WNV infection relies on virus identification by RT-PCR or on specific antibody detection by serological tests, such as ELISA or virus-neutralization. These methods usually require a preparation of the whole virus as antigen, entailing biosafety issues and therefore requiring BSL-3 facilities. For this reason, recombinant antigenic structures enabling effective antibody recognition comparable to that of the native virions, would be advantageous as diagnostic reagents...
February 10, 2018: Diagnostic Microbiology and Infectious Disease
Eman Farid, Mohammed Al-Biltagi
In Bahrain, adequate epidemiological information is lacking concerning the rate of EBV infection, which could be helpful in order to develop measures to protect against EBV infections. The aim of this study, was to investigate the trend of EBV infection in Bahrain over a 15-year period, 2001-2015. The EBV serological results of 10 560 patients with possible EBV infection were evaluated. Samples taken at the Salmaniya Medical Complex during 2001-2015 were included. The presence or absence of EBV viral capsid antigen (VCA) IgG, VCA IgM and EBV nuclear antigen (EBNA) IgG antibodies was recorded...
March 5, 2018: Eastern Mediterranean Health Journal, la Revue de Santé de la Méditerranée Orientale
Lipsa Dash, Saravanan Subramaniam, Sagar A Khulape, Bikash Ranjan Prusty, Kamal Pargai, Shirish D Narnaware, Niteen V Patil, Bramhadev Pattnaik
Foot-and-mouth disease (FMD) is an acute, highly contagious, and economically devastating viral disease of domestic and wildlife species. For effective implementation of FMD control program, there is an imperative need for developing a rapid, sensitive, and specific diagnostics which help in the identification of serotypes involved in the outbreaks. The humoral immune response of the Camelidae is unique since in these animals 75% of circulating antibodies are constituted by heavy-chain antibodies and 25% are conventional immunoglobulin with two identical heavy chains...
March 12, 2018: Animal Biotechnology
Anvita Bhargava, Xavier Lahaye, Nicolas Manel
The nuclear envelope is a physical barrier that isolates the cellular DNA from the rest of the cell, thereby limiting pathogen invasion. The Human Immunodeficiency Virus (HIV) has a remarkable ability to enter the nucleus of non-dividing target cells such as lymphocytes, macrophages and dendritic cells. While this step is critical for replication of the virus, it remains one of the less understood aspects of HIV infection. Here, we review the viral and host factors that favor or inhibit HIV entry into the nucleus, including the viral capsid, integrase, the central viral DNA flap, and the host proteins CPSF6, TNPO3, Nucleoporins, SUN1, SUN2, Cyclophilin A and MX2...
February 27, 2018: Cytokine & Growth Factor Reviews
Nada Harik, Roberta L DeBiasi
Nonpolio enteroviruses and parechoviruses are frequent causes of neonatal infection. Clinical manifestations of infection range from asymptomatic infection to mild infection without sequelae to septic shock with muiltiorgan failure. Neonates with clinically apparent infection typically have mothers and/or other contacts with recent symptoms consistent with a viral illness. Severe neonatal infection with nonpolio enterovirus or parechovirus cannot be differentiated clinically from serious bacterial infection...
March 8, 2018: Seminars in Perinatology
Jon Gil-Ranedo, Eva Hernando, Noelia Valle, Laura Riolobos, Beatriz Maroto, José M Almendral
The T1 parvovirus Minute Virus of Mice (MVM) was used to study the roles that phosphorylation and N-terminal domains (Nt) configuration of capsid subunits may play in icosahedral nuclear viruses assembly. In synchronous MVM infection, capsid subunits newly assembled as two types of cytoplasmic trimeric intermediates (3VP2, and 1VP1:2VP2) harbored a VP1 phosphorylation level fivefold higher than that of VP2, and hidden Nt. Upon nuclear translocation at S phase, VP1-Nt became exposed in the heterotrimer and subsequent subviral assembly intermediates...
March 7, 2018: Virology
Melvin Y Rincon, Filip de Vin, Sandra I Duqué, Shelly Fripont, Stephanie A Castaldo, Jessica Bouhuijzen-Wenger, Matthew G Holt
Until recently, adeno-associated virus 9 (AAV9) was considered the AAV serotype most effective in crossing the blood-brain barrier (BBB) and transducing cells of the central nervous system (CNS), following systemic injection. However, a newly engineered capsid, AAV-PHP.B, is reported to cross the BBB at even higher efficiency. We investigated how much we could boost CNS transgene expression by using AAV-PHP.B carrying a self-complementary (sc) genome. To allow comparison, 6 weeks old C57BL/6 mice received intravenous injections of scAAV2/9-GFP or scAAV2/PHP...
March 9, 2018: Gene Therapy
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