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Order Sepolyvirales
Published in Paul Pumpens, Peter Pushko, Philippe Le Mercier, Virus-Like Particles, 2022
Paul Pumpens, Peter Pushko, Philippe Le Mercier
The MPyV VP1 protein was expressed in E. coli as early as the 1980s (Leavitt et al. 1985) and appeared as dissociated pentameric capsomeres capable of the spontaneous in vitro assembly into the virion-like structures and polymorphic aggregates (Salunke et al. 1986, 1989). The C-terminal truncation of the VP1 protein blocked assembly of capsomeres (Garcea et al. 1987), but its N-terminus was found to be responsible for DNA binding and nuclear localization (Moreland et al. 1991). The E. coli-produced proteins VP2 and VP3 of MPyV interacted with the purified VP1 in vitro, affected the biochemical properties of the VP1 capsomeres, and changed their epitope accessibility (Cai et al. 1994; Delos et al. 1995). The crystal structure of a complex of the single VP2/VP3 copy with the pentameric major capsid protein VP1 was determined at 2.2 Å resolution (Chen XS et al. 1998). Braun et al. (1999) expressed the VP1 gene in E. coli as a fusion with the completely removable N-terminal His6 tag. The pentameric morphology of the recombinant VP1 protein was confirmed by electron microscopy after affinity chromatography and factor Xa cleavage under conditions of low ionic strength. The self-assembly of the VP1 VLPs was induced by increasing the ionic strength with (NH4)2SO4. These VP1 VLPs were packed in vitro with antisense oligonucleotides and plasmid DNA (Braun et al. 1999). Furthermore, Yang and Chen (2000) generated the E. coli-produced VP1-based MPyV pseudovirions, both in vitro and in vivo, which were able to transfer the exogenous DNA with following expression of the encoded reporter genes to mammalian cells or to the livers of Wistar rats. Stubenrauch et al. (2000) inserted a polyionic sequence of eight glutamic acid residues into the exposed VP1 loop to improve purification properties of the MPyV VP1 VLPs in E. coli.
Human Noroviruses
Published in Dongyou Liu, Handbook of Foodborne Diseases, 2018
G. Sanchez, W. Randazzo, D.H. D'Souza
VLPs have similar capsid and binding characteristics as wild-type HNoVs and are produced in high amounts by expression of the VP1 capsid protein in eukaryotic expression vectors (baculoviruses, yeast, and plants).222,223 These candidate vaccines target the major capsid protein VP1 and have been studied in preclinical trials using several animal models including mice, gnotobiotic pigs, rabbits, and chimpanzees.55,224–226 Preclinical studies in mice showed that intranasal, oral, or parenteral delivery of VLPs induced serum and mucosal immunity, with improved mucosal immunity when coadministered with a mucosal adjuvant.227,228 HNoV GII.4-derived VLPs following cross-variant or homo-variant challenge were shown to provide partial protection against diarrhea in gnotobiotic pigs,225 and another one could elicit antibody responses to a wide range of GII.4 variants.221,229 Varied formulations and administration routes (intramuscular, intranasal, and oral) of HNoV vaccines in preclinical or clinical trials are also ongoing or being researched.230,231 A bivalent vaccine is reported to be in phase II clinical trials, which is based on genotype GI.1 and a consensus GII.4 recombinant VLP, designed from a consensus sequence of three GII.4 variants (Henry_2001, Yerseke_2006a, and Den Haag_2006b) using the Houston virus (Henry_2001 variant) as the backbone.221,231,232 With regard to mucosal vaccines, Balb/c mice immunized intramuscularly with HNoV GII.4 VLPs completely lacked IgA, while intranasal immunization was shown to elicit HNoV-specific serum and mucosal IgG and IgA antibodies with strong correlation of the IgA levels in the nasal lavage to blocking activity.233 Mucosal vaccines and VLPs may be a likely approach for HNoV-naive pediatric and perhaps even elderly populations and against emerging and recombinant HNoV strains.222
Parabacteroides distasonis: intriguing aerotolerant gut anaerobe with emerging antimicrobial resistance and pathogenic and probiotic roles in human health
Published in Gut Microbes, 2021
Jessica C. Ezeji, Daven K. Sarikonda, Austin Hopperton, Hailey L. Erkkila, Daniel E. Cohen, Sandra P. Martinez, Fabio Cominelli, Tomomi Kuwahara, Armand E. K. Dichosa, Caryn E. Good, Michael R. Jacobs, Mikhail Khoretonenko, Alida Veloo, Alexander Rodriguez-Palacios
Elegantly, Quaiser et al.132 showed through Blast searches that the major capsid protein VP1 sequences from the assembled viral wetland genomes showed similarities to VP1 proteins encoded in the P. merdae and P. distasonis genomes.2 The Parabacteroides VP1 genes show that genes encoding for homolog VP2 and VP4 genes (other capsular phage proteins) were juxtaposed next to the bacterial VP1 genes, supporting the presence of a prophage Microviridae in both Parabacteroides species. Comparing their organization, the identified prophage regions flanking the VP1 gene (5 kbp) were extracted from the genomes and considered circular for analysis, using the VP1 gene as an arbitrary start. Synteny analysis showed, remarkably, that the prophages have the same gene order in such bacteria (P. distasonis: VP1-ORF1-ORF2-ORF3-VP2-VP4, and P. merdae: VP1-ORF1-VP2-VP4) suggesting that both have a common functional prophage ancestor. The gene coding for the arbitrarily assigned protein ORF1 downstream of VP1 in both bacteria were specific to each prophage and did not match to genes from other Microviridae or in NCBI non-redundant databases. This strengthens the hypothesis that these prophages represent a distinct subfamily of Microviridae, suggesting the relevance of this genus and species in water sources previously described.
Understanding the relationship between norovirus diversity and immunity
Published in Gut Microbes, 2021
Lauren A. Ford-Siltz, Kentaro Tohma, Gabriel I. Parra
Noroviruses are small, icosahedral, non-enveloped, positive-sense, single-stranded RNA viruses that infect different mammal species. The human norovirus genome is ~7.5 kb in length and is divided into three open reading frames (ORF1-3). Upon entry into susceptible cells, the ORF1 is immediately translated as a polyprotein that is processed co- and post-translationally by the viral protease to yield six nonstructural (NS) proteins required for viral replication: NS1/2 (N-term), NS3 (helicase), NS4 (3A-like), NS5 (VPg), NS6 (protease), and NS7 (RNA-dependent RNA polymerase, RdRp). ORF2, which encodes the major capsid protein VP1, and ORF3, which encodes the minor capsid protein VP2, are translated from the subgenomic RNA. The viral capsid presents a T = 3 icosahedral structure consisting of 90 VP1 dimers, and an undetermined quantity of VP2 (Figure 1, panel A).1,2 Heterologous expression of VP1 leads to the self-assembly of virus-like particles (VLPs), which are structurally- and antigenically similar to the native virion, although viruses and VLPs with different sizes and symmetries have also been described.3–5 In the absence of a robust cell culture system for viral cultivation, VLPs have been instrumental in vaccine research.
Vaccines against gastroenteritis, current progress and challenges
Published in Gut Microbes, 2020
Hyesuk Seo, Qiangde Duan, Weiping Zhang
There are several norovirus vaccine candidates under clinical or preclinical studies. Because norovirus is unculturable under current cell culture system, developing attenuated whole-cell vaccines becomes prohibitable. Consequently, calicivirus vaccine candidates under investigation are largely based on viral proteins. Norovirus major capsid protein VP1, when expressed in eukaryotic cells, forms virus-like particles (VLP) to exhibit antigenicity similarly to native viral particles. Additionally, the P domain of VP1 after being linked to a polypeptide and expressed in cell culture also aggregates into particles (P particle). Therefore, VP1 virus-like particles and P particles of global pandemic genotype GII.4 and the regional endemic GI genotypes are the primary antigens for norovirus vaccine development.