scholarly journals Cryo-EM structure of enteric adenovirus HAdV-F41 highlights structural variations among human adenoviruses

2021 ◽  
Vol 7 (9) ◽  
pp. eabd9421
Author(s):  
Marta Pérez-Illana ◽  
Marta Martínez ◽  
Gabriela N. Condezo ◽  
Mercedes Hernando-Pérez ◽  
Casandra Mangroo ◽  
...  
Keyword(s):  
Oral Delivery ◽  
Viral Gastroenteritis ◽  
Coat Proteins ◽  
Structural Variations ◽  
Starting Point ◽  
Enteric Adenovirus ◽  
Protein Ix ◽  
Capsid Stability ◽  
Harsh Conditions ◽  
Enteric Adenoviruses

Enteric adenoviruses, one of the main causes of viral gastroenteritis in the world, must withstand the harsh conditions found in the gut. This requirement suggests that capsid stability must be different from that of other adenoviruses. We report the 4-Å-resolution structure of a human enteric adenovirus, HAdV-F41, and compare it with that of other adenoviruses with respiratory (HAdV-C5) and ocular (HAdV-D26) tropisms. While the overall structures of hexon, penton base, and internal minor coat proteins IIIa and VIII are conserved, we observe partially ordered elements reinforcing the vertex region, which suggests their role in enhancing the physicochemical capsid stability of HAdV-F41. Unexpectedly, we find an organization of the external minor coat protein IX different from all previously characterized human and nonhuman mastadenoviruses. Knowledge of the structure of enteric adenoviruses provides a starting point for the design of vectors suitable for oral delivery or intestinal targeting.

scholarly journals Cryo-EM structure of enteric adenovirus HAdV-F41 highlights structural divergence among human adenoviruses

2020 ◽  
Author(s):  
Marta Pérez-Illana ◽  
Marta Martínez ◽  
Gabriela N. Condezo ◽  
Mercedes Hernando-Pérez ◽  
Casandra Mangroo ◽  
...  
Keyword(s):  
Oral Delivery ◽  
Viral Gastroenteritis ◽  
Coat Proteins ◽  
Successful Infection ◽  
Starting Point ◽  
Enteric Adenovirus ◽  
Protein Ix ◽  
Capsid Stability ◽  
Harsh Conditions ◽  
Enteric Adenoviruses

AbstractEnteric adenoviruses are one of the main causes of viral gastroenteritis in the world. To carry out a successful infection, the virions must withstand the harsh conditions found in the gut. This requirement suggests that capsid stability must be different from that of other adenoviruses. We have determined the structure of a human enteric adenovirus, HAdV-F41, at 4.0 Å resolution by single particle averaging cryo-electron microscopy, and compared it with that of other adenoviruses with respiratory (HAdV-C5) and ocular (HAdV-D26) tropisms. While the overall structures of hexon, penton base and internal minor coat proteins IIIa and VIII are conserved, we observe partially ordered elements reinforcing the vertex region, which suggests their role in enhancing the physicochemical capsid stability of HAdV-F41. Unexpectedly, we find an organization of the external minor coat protein IX different from all previously characterized human and non-human mastadenoviruses. Knowledge of the structure of enteric adenoviruses can provide a starting point for the design of vectors suitable for oral delivery or intestinal targeting.

scholarly journals Near Atomic Structure of an Atadenovirus Reveals a Conserved Capsid-Binding Motif and Intergenera Variations in Cementing Proteins

2020 ◽  
Author(s):  
Roberto Marabini ◽  
Gabriela N. Condezo ◽  
Josué Gómez-Blanco ◽  
Carmen San Martín
Keyword(s):  
Duplication Event ◽  
Specific Protein ◽  
Mammalian Host ◽  
Binding Motif ◽  
Coat Proteins ◽  
Human Adenoviruses ◽  
High Resolution Structure ◽  
Attachment Proteins ◽  
Protein Ix ◽  
Capsid Stability

AbstractLittle is known about the basic biology of non-human adenoviruses, which could be alternative vectors free of issues posed by preexisting immunity to human adenoviruses. We present the cryo-EM structure of a lizard atadenovirus, LAdV-2, at 3.4 Å resolution. This is the first high resolution structure of an adenovirus with non-mammalian host, and of an adenovirus not belonging to the Mastadenovirus genus. Atadenovirus capsids contain genus specific proteins LH3, p32k, and LH2, and are more thermostable than the more studied human adenoviruses. We find a large conformational difference in the internal vertex protein IIIa between mast- and atadenoviruses, induced by the presence of an extended polypeptide in the region. This polypeptide, as well as α-helical clusters located beneath the icosahedral facet, likely correspond to proteins LH2 and p32k. The external genus specific protein LH3, with a trimeric β-helix fold typical of bacteriophage host attachment proteins, contacts the hexon shell surface via a triskelion structure identical to that used by protein IX in human AdV, revealing a conserved capsid-binding motif and a possible gene duplication event. Altogether, this work shows how the network of minor coat proteins differs between AdV genera and relates to virus evolution and capsid stability properties.

scholarly journals Microparticles and Nanoparticles from Plants—The Benefits of Bioencapsulation

Vaccines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 369
Author(s):  
Jennifer Schwestka ◽  
Eva Stoger
Keyword(s):  
Targeted Delivery ◽  
Oral Delivery ◽  
Protective Coatings ◽  
Production Costs ◽  
Cell Wall Proteins ◽  
Production Host ◽  
And Storage ◽  
Harsh Conditions ◽  
Encapsulation Methods

The efficacy of drugs and vaccines depends on their stability and ability to interact with their targets in vivo. Many drugs benefit from encapsulation, which protects them from harsh conditions and allows targeted delivery and controlled release. Although many encapsulation methods are inexpensive, such as the formulation of tablets for oral delivery, others require complex procedures that add significantly to production costs and require low-temperature transport and storage, making them inaccessible in developing countries. In this review we consider the benefits of encapsulation technologies based on plants. Plant-derived biopolymers such as starch and the maize storage protein zein are already used as protective coatings, but plant cells used as production host provide natural in vivo bioencapsulation that survives passage through the stomach and releases drugs in the intestine, due to the presence of microbes that can digest the cell wall. Proteins can also be encapsulated in subcellular compartments such as protein bodies, which ensure stability and activity while often conferring additional immunomodulatory effects. Finally, we consider the incorporation of drugs and vaccines into plant-derived nanoparticles assembled from the components of viruses. These are extremely versatile, allowing the display of epitopes and targeting peptides as well as carrying cargoes of drugs and imaging molecules.

Detection and molecular characterization of enteric adenovirus in treated wastewater in the Brazilian Federal District

2021 ◽  
Vol 3 (7) ◽  
Author(s):  
T. S. C. Quintão ◽  
F. G. Silva ◽  
A. L. Pereira ◽  
W. N. Araújo ◽  
P. M. Oliveira ◽  
...  
Keyword(s):  
Phylogenetic Analysis ◽  
Wastewater Treatment ◽  
Wastewater Treatment Plants ◽  
Federal District ◽  
Treated Wastewater ◽  
Conventional Pcr ◽  
Rainfall Index ◽  
Enteric Adenovirus ◽  
Enteric Adenoviruses

AbstractHuman enteric viruses, such as enteric adenoviruses (HAdV), are known to be involved with gastrointestinal disorders, especially acute gastroenteritis. Several studies have used HAdV as an indicator of water quality, since they are considered highly stable and widely distributed viruses in water matrices. The aim of this study was to detect and genotype HAdVs in water matrices impacted by discharges of treated effluents from wastewater treatment plants (WWTPs). Wastewater treatment plants from the sanitary system of the Brazilian Federal District were assessed in 2018 and 2019. Samples were collected upstream and downstream from discharge points for each WWTP. Viral concentration based on adsorption-elution and conventional PCR was used for molecular detection, and positive samples were sequenced for phylogenetic analysis. Pluviosity data for the period in which the samples were collected were obtained. Our results demonstrated the presence of HAdVs in 27.2% (61/224) of the samples. The positivity was significantly higher in downstream samples compared to upstream. Moreover, the HAdV positivity was higher in downstream samples collected from receiving water bodies impacted by secondary-level WWTPs in comparison with those impacted by tertiary-level WWTPs. Phylogenetic analysis demonstrated the presence of genotypes 40 and 41, with prevalence of HAdV genotype 41. Despite the predominance of HAdV-41, an increasing frequency of the HAdV-40 was associated with higher pluviosity. In conclusion, this study is the first documentation in the Brazilian Federal District dealing with the prevalence and diversity of HAdVs in several WWTP, along with their correlation with rainfall index.

scholarly journals Enhancement of Enteric Adenovirus Cultivation by Viral Transactivator Proteins

2010 ◽  
Vol 76 (8) ◽  
pp. 2509-2516 ◽  
Author(s):  
Misoon Kim ◽  
Mi Young Lim ◽  
GwangPyo Ko
Keyword(s):  
Cell Line ◽  
Cytopathic Effect ◽  
Cell Cultivation ◽  
Promoter Regions ◽  
Viral Dna ◽  
Viral Transactivator ◽  
Food Borne ◽  
B Virus ◽  
Enteric Adenovirus ◽  
Enteric Adenoviruses

ABSTRACT Human enteric adenoviruses (HAdVs; serotypes 40 and 41) are important waterborne and food-borne pathogens. However, HAdVs are fastidious, are difficult to cultivate, and do not produce a clear cytopathic effect during cell culture within a reasonable time. Thus, we examined whether the viral transactivator proteins cytomegalovirus (CMV) IE1 and hepatitis B virus (HBV) X promoted the multiplication of HAdVs. Additionally, we constructed a new 293 cell line expressing CMV IE1 protein for cultivation assays. We analyzed the nucleic acid sequences of the promoter regions of both E1A and hexon genes, which are considered to be the most important regions for HAdV replication. Expression of either HBV X or CMV IE1 protein significantly increased the promoter activities of E1A and hexon genes of HAdVs by as much as 14-fold during cell cultivation. The promotion of HAdV expression was confirmed by increased levels of both adenoviral DNA and mRNA expression. Finally, the newly developed 293 cell line expressing CMV IE1 protein showed an increase in viral DNA ranging from 574% to 619% compared with the conventional 293 cell line. These results suggest that the newly constructed cell line could be useful for efficient cultivation and research of fastidious HAdVs.

scholarly journals Epidemiology of enteric adenovirus infection in prospectively monitored Argentine families

1992 ◽  
Vol 109 (3) ◽  
pp. 539-546 ◽  
Author(s):  
A. S. Mistchenko ◽  
K. H. Huberman ◽  
J. A. Gomez ◽  
S. Grinstein
Keyword(s):  
Buenos Aires ◽  
Blot Hybridization ◽  
Dot Blot ◽  
Severe Diarrhoea ◽  
Natural Conditions ◽  
Dot Blot Hybridization ◽  
Faecal Samples ◽  
Enteric Adenovirus ◽  
Enteric Adenoviruses

SUMMARYTo examine the role of enteric adenoviruses (EAV) in an urban area of Buenos Aires (Argentina), we prospectively studied faecal samples from 49 families of newborns. These were monitored weekly for diarrhoea for 2 years.A total of 180 samples from cases of diarrhoea and 766 samples obtained during diarrhoea-free periods were studied by dot-blot hybridization with an EAV-specific DNA probe. EAV were found in 6/180 (3·3%) cases of diarrhoea and 6/766 (0·8%) asymptomatic samples (P < 0·015). Incidence of EAV was 3·9 cases per 100 person-years in children < 60 months old. EAV-related diarrhoeas were slight and of short duration. In addition, 129 faeces from hospital out-patients, 1–30 months old, were also studied. EAV was identified in 7/129 cases (5·4%). These cases were 9·5 ±3·5 months old and the diarrhoea was mild or severe, of 3±1·5 days of duration.We suggest that EAV are low-risk causes of diarrhoea under natural conditions, although a few children may develop more severe diarrhoea. The diagnosis of EAV needs to be considered in these patients.

Fermentation of bioactive solid lipid nanoparticles by human gut microflora

2016 ◽  
Vol 7 (1) ◽  
pp. 516-529 ◽  
Author(s):  
Ana Raquel Madureira ◽  
Débora Campos ◽  
Beatriz Gullon ◽  
Cláudia Marques ◽  
Luís M. Rodríguez-Alcalá ◽  
...  
Keyword(s):  
Phenolic Compounds ◽  
Intestinal Epithelium ◽  
Solid Lipid Nanoparticles ◽  
Oral Delivery ◽  
Lipid Nanoparticles ◽  
Gut Microflora ◽  
Human Gut ◽  
Solid Lipid ◽  
Harsh Conditions

Solid lipid nanoparticles (SLNs) can be used for oral delivery of phenolic compounds in order to protect them from the harsh conditions of digestion and improve their bioavailability in the intestinal epithelium.

scholarly journals A hydrophobic network: Intersubunit and intercapsomer interactions stabilizing the bacteriophage P22 capsid

2019 ◽  
Author(s):  
Kunica Asija ◽  
Carolyn M. Teschke
Keyword(s):  
Coat Protein ◽  
Hydrophobic Interactions ◽  
Protein Structures ◽  
Antiviral Drug ◽  
Coat Proteins ◽  
Bacteriophage P22 ◽  
Outer Periphery ◽  
Phage P22 ◽  
P Domain ◽  
Capsid Stability

AbstractdsDNA tailed phages and herpesviruses assemble their capsids using coat proteins that have the ubiquitous HK97 fold. Though this fold is common, we do not have a thorough understanding of the different ways viruses adapt it to maintain stability in various environments. The HK97-fold E-loop, which connects adjacent subunits at the outer periphery of capsomers, has been implicated in capsid stability. Here we show that in bacteriophage P22, residue W61 at the tip of the E-loop plays a role in stabilizing procapsids and in maturation. We hypothesize that a hydrophobic pocket is formed by residues I366 and W410 in the P-domain of a neighboring subunit within a capsomer, into which W61 fits like a peg. In addition, W61 likely bridges to residues A91 and L401 in P-domain loops of an adjacent capsomer, thereby linking the entire capsid together with a network of hydrophobic interactions. There is conservation of this hydrophobic network in the distantly related P22-like phages, indicating that this structural feature is likely important for stabilizing this family of phages. Thus, our data shed light on one of the varied elegant mechanisms used in nature to consistently build stable viral genome containers through subtle adaptation of the HK97 fold.IMPORTANCESimilarities in assembly reactions and coat protein structures of the dsDNA tailed phages and herpesviruses make phages ideal models to understand capsid assembly and identify potential targets for antiviral drug discovery. The coat protein E-loops of these viruses are involved in both intra-and intercapsomer interactions. In phage P22, hydrophobic interactions peg the coat protein subunits together within a capsomer, where the E-loop hydrophobic residue W61 of one subunit packs into a pocket of hydrophobic residues I366 and W410 of the adjacent subunit. W61 also makes hydrophobic interactions with A91 and L401 of a subunit in an adjacent capsomer. We show these intra-and intercapsomer hydrophobic interactions form a network crucial to capsid stability and proper assembly.

scholarly journals Recognition of adenovirus types in faecal samples by Southern hybridization in South Australia

1994 ◽  
Vol 112 (3) ◽  
pp. 603-613 ◽  
Author(s):  
L. D. Mickan ◽  
T.-W. Kok
Keyword(s):  
Enzyme Immunoassay ◽  
Genomic Dna ◽  
Southern Hybridization ◽  
South Australia ◽  
Late Winter ◽  
Viral Gastroenteritis ◽  
Southern Hybridization Analysis ◽  
Restriction Patterns ◽  
Faecal Samples ◽  
Enteric Adenovirus

SUMMARYThe distribution of adenovirus types in faecal samples of patients with suspected viral gastroenteritis from South Australia was determined during the 12-month period, July 1991–June 1992. There were 3299 samples tested and 226 (6·9%) were positive for adenovirus by enzyme immunoassay. Of these 226 samples. 154 (68%) were typed directly using virus DNA extracted from the faecal samples according to theSmaI,HindIII andBstEII restriction patterns and Southern hybridization analysis with pooled viral genomic DNA probes. In this group, 86% of the samples were from patients who were < 3 years of age. Enteric adenovirus types 40 and 41 accounted for 20 and 40% respectively, of these samples, and types 1, 2, 3, 5, 6, 7 and 31 comprised the remainder. Type 40 was detected mainly in the winter and spring periods, and type 41 predominated in the autumn period. The majority of the non-enteric types were found during the late winter and spring periods.

scholarly journals Functional Analysis of Adenovirus Protein IX Identifies Domains Involved in Capsid Stability, Transcriptional Activity, and Nuclear Reorganization

2001 ◽  
Vol 75 (15) ◽  
pp. 7131-7141 ◽  
Author(s):  
Manuel Rosa-Calatrava ◽  
Linda Grave ◽  
Francine Puvion-Dutilleul ◽  
Bruno Chatton ◽  
Claude Kedinger
Keyword(s):  
Self Assembly ◽  
Transcriptional Activity ◽  
Nuclear Retention ◽  
Nuclear Reorganization ◽  
Infected Cells ◽  
Nuclear Structures ◽  
The Stability ◽  
Protein Ix ◽  
Capsid Stability ◽  
Expression Program

ABSTRACT The product of adenovirus (Ad) type 5 gene IX (pIX) is known to actively participate in the stability of the viral icosahedron, acting as a capsid cement. We have previously demonstrated that pIX is also a transcriptional activator of several viral and cellular TATA-containing promoters, likely contributing to the transactivation of the Ad expression program. By extensive mutagenesis, we have now delineated the functional domains involved in each of the pIX properties: residues 22 to 26 of the highly conserved N-terminal domain are crucial for incorporation of the protein into the virion; specific residues of the C-terminal leucine repeat are responsible for pIX interactions with itself and possibly other proteins, a property that is critical for pIX transcriptional activity. We also show that pIX takes part in the virus-induced nuclear reorganization of late infected cells: the protein induces, most likely through self-assembly, the formation of specific nuclear structures which appear as dispersed nuclear globules by immunofluorescence staining and as clear amorphous spherical inclusions by electron microscopy. The integrity of the leucine repeat appears to be essential for the formation and nuclear retention of these inclusions. Together, our results demonstrate the multifunctional nature of pIX and provide new insights into Ad biology.

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