Adenovirus Virion Stability and the Viral Genome: Size Matters

Kennedy, Michael A.; Parks, Robin J.

doi:10.1038/mt.2009.202

Cited by 56 publications

(41 citation statements)

References 34 publications

(22 reference statements)

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“…Figure 2 shows the number-based hydrodynamic diameter distribution of HAdV 40 as a function of pH, and Table 2 summarizes the hydrodynamic diameters over a wide range of pH values. At pH 5.8 (unadjusted), pH 6.7, and pH 7.6, the number-based average hydrodynamic diameters of HAdV 40 (d HAdV h ) ranged from 94 Ϯ 3 nm to 102 Ϯ 9 nm, agreeing with typical size values reported earlier for HAdVs of different serotypes (44)(45)(46). The small increase in the hydrodynamic diameter relative to the diameter determined by TEM may have stemmed from fibers on the HAdV 40 surface (30, 47) that we did not take into account when estimating HAdV 40 diameters from TEM images.…”

Section: Resultssupporting

confidence: 76%

Elution Is a Critical Step for Recovering Human Adenovirus 40 from Tap Water and Surface Water by Cross-Flow Ultrafiltration

Shi

Xagoraraki

Parent

et al. 2016

Appl Environ Microbiol

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This paper examines the recovery of the enteric adenovirus human adenovirus 40 (HAdV 40) by cross-flow ultrafiltration and interprets recovery values in terms of physicochemical interactions of virions during sample concentration. Prior to ultrafiltration, membranes were either blocked by exposure to calf serum (CS) or coated with a polyelectrolyte multilayer (PEM). HAdV 40 is a hydrophobic virus with a point of zero charge between pH 4.0 and pH 4.3. In accordance with predictions from the extended Derjaguin-Landau-Verwey-Overbeek theory, the preelution recovery of HAdV (r pre ) from deionized water was higher with PEMcoated membranes (r pre PEM ‫؍‬ 74.8% ؎ 9.7%) than with CS-blocked membranes (r pre CS ‫؍‬ 54.1% ؎ 6.2%). With either membrane type, the total virion recovery after elution (r post ) was high for both deionized water (r post PEM ‫؍‬ 99.5% ؎ 6.6% and r post CS ‫؍‬ 98.8% ؎ 7.7%) and tap water (r post PEM ‫؍‬ 89% ؎ 15% and r post CS ‫؍‬ 93.7% ؎ 6.9%). The nearly 100% recoveries suggest that the polyanion (sodium polyphosphate) and surfactant (Tween 80) in the eluent disrupt electrostatic and hydrophobic interactions between the virion and the membrane. Addition of EDTA to the eluent greatly improved the elution efficacy (r post CS ‫؍‬ 88.6% ؎ 4.3% and r post PEM ‫؍‬ 87.0% ؎ 6.9%) with surface water, even when the organic carbon concentration in the water was high (9.4 ؎ 0.1 mg/liter). EDTA likely disrupts cation bridging between virions and particles in the feed water matrix or the fouling layer on the membrane surface. For complex water matrices, the eluent composition is the most important factor for achieving high virion recovery. IMPORTANCEHerein we present the results of a comprehensive physicochemical characterization of HAdV 40, an important human pathogen. The data on HAdV 40 surface properties enabled rigorous modeling to gain an understanding of the energetics of virion-virion and virion-filter interactions. Cross-flow filtration for concentration and recovery of HAdV 40 was evaluated, with postelution recoveries from ultrapure water (99%), tap water (ϳ91%), and high-carbon-content surface water (ϳ84%) being demonstrated. These results are significant because of the very low adenovirus recoveries that have been reported, to date, for other methods. The recovery data were interpreted in terms of specific interactions, and the eluent composition was designed accordingly to maximize HAdV 40 recovery. P athogenic microorganisms cause many waterborne diseases, and the World Health Organization reports that water supply contamination leads to 842,000 deaths annually (1). Along with caliciviruses (e.g., norovirus), enteroviruses (e.g., poliovirus, coxsackievirus, and echovirus), and hepatitis A viruses, human adenovirus (HAdV) is one of the viral pathogens in EPA contaminant candidate lists 3 and 4 and is the second-leading cause of childhood gastroenteritis worldwide (2-4). Most cases of adenovirusassociated gastroenteritis stem from HAdV serotypes 40 and 41 (5), which are relatively resis...

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Section: Resultssupporting

confidence: 76%

Elution Is a Critical Step for Recovering Human Adenovirus 40 from Tap Water and Surface Water by Cross-Flow Ultrafiltration

Shi

Xagoraraki

Parent

et al. 2016

Appl Environ Microbiol

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“…Although similar instability is not observed for L-leucine 14 through XRD, a failure to properly incorporate the AdHu5LacZ vector within the matrix renders 15 it a poor excipient formulation for long term storage. 16 …”

mentioning

confidence: 99%

Evaluation of excipients for enhanced thermal stabilization of a human type 5 adenoviral vector through spray drying

Leclair

Cranston

Xing

et al. 2016

International Journal of Pharmaceutics

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4We have produced a thermally stable recombinant human type 5 adenoviral vector 5 (AdHu5) through spray drying with three excipient formulations (L-leucine, lactose/trehalose 6 and mannitol/dextran). Spray drying leads to immobilization of the viral vector which is believed 7 to prevent viral protein unfolding, aggregation and inactivation. The spray dried powders were 8 characterized by scanning electron microscopy, differential scanning calorimetry, Karl Fischer 9 titrations, and X-ray diffraction to identify the effects of temperature and atmospheric moisture 10 on the immobilizing matrix. Thermal stability of the viral vector was confirmed in vitro by 11 infection of A549 lung epithelial cells. Mannitol/dextran powders showed the greatest 12 improvement in thermal stability with almost no viral activity loss after storage at 20°C for 90 13 days (0.7 ± 0.3 log TCID 50 ) which is a significant improvement over the current -80 o C storage 14 protocol. Furthermore, viral activity was retained over short term exposure (72 hours) to 15 temperatures as high as 55°C. Conversely, all powders exhibited activity loss when subjected to 16 moisture due to amplified molecular motion of the matrix. Overall, a straightforward method 17 ideal for the production of thermally stable vaccines has been demonstrated through spray drying 18AdHu5 with a blend of mannitol and dextran and storing the powder under low humidity 19 conditions. 20 21

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“…The high resistance level of AdV2 is likely to be associated with its size and structure. Adenoviruses range in size from 70 to 100 nm (30), making them much larger than X174 (27 to 33 nm) and MNV (28 to 35 nm) (31,32). In addition to their large size, adenoviruses have double-stranded DNA, unlike other viruses, and are resistant to various environmental stresses such as heat and UV radiation (33,34).…”

Section: Discussionmentioning

confidence: 99%

Antiviral Properties of Silver Nanoparticles on a Magnetic Hybrid Colloid

Park

Kim

et al. 2014

Appl Environ Microbiol

129

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c Silver nanoparticles (AgNPs) are considered to be a potentially useful tool for controlling various pathogens. However, there are concerns about the release of AgNPs into environmental media, as they may generate adverse human health and ecological effects. In this study, we developed and evaluated a novel micrometer-sized magnetic hybrid colloid (MHC) decorated with variously sized AgNPs (AgNP-MHCs). After being applied for disinfection, these particles can be easily recovered from environmental media using their magnetic properties and remain effective for inactivating viral pathogens. We evaluated the efficacy of AgNP-MHCs for inactivating bacteriophage X174, murine norovirus (MNV), and adenovirus serotype 2 (AdV2). These target viruses were exposed to AgNP-MHCs for 1, 3, and 6 h at 25°C and then analyzed by plaque assay and real-time TaqMan PCR. The AgNP-MHCs were exposed to a wide range of pH levels and to tap and surface water to assess their antiviral effects under different environmental conditions. Among the three types of AgNP-MHCs tested, Ag30-MHCs displayed the highest efficacy for inactivating the viruses. The X174 and MNV were reduced by more than 2 log 10 after exposure to 4.6 ؋ 10 9 Ag30-MHCs/ml for 1 h. These results indicated that the AgNP-MHCs could be used to inactivate viral pathogens with minimum chance of potential release into environment. With recent advances in nanotechnology, nanoparticles have been receiving increased attention worldwide in the fields of biotechnology, medicine, and public health (1, 2). Owing to their high surface-to-volume ratio, nano-sized materials, typically ranging from 10 to 500 nm, have unique physicochemical properties compared with those of larger materials (1). The shape and size of nanomaterials can be controlled, and specific functional groups can be conjugated on their surfaces to enable interactions with certain proteins or intracellular uptake (3-5).Silver nanoparticles (AgNPs) have been widely studied as an antimicrobial agent (6). Silver is used in the creation of fine cutlery, for ornamentation, and in therapeutic agents. Silver compounds such as silver sulfadiazine and certain salts have been used as wound care products and as treatments for infectious diseases due to their antimicrobial properties (6, 7). Recent studies have revealed that AgNPs are very effective for inactivating various types of bacteria and viruses (8-11). AgNPs and Ag ϩ ions released from AgNPs interact directly with phosphorus-or sulfur-containing biomolecules, including DNA, RNA, and proteins (12-14). They have also been shown to generate reactive oxygen species (ROS), causing membrane damage in microorganisms (15). The size, shape, and concentration of AgNPs are also important factors that affect their antimicrobial capabilities (8,10,13,16,17).Previous studies have also highlighted several problems when AgNPs are used for controlling pathogens in a water environment. First, existing studies on the effectiveness of AgNPs for inactivating viral pathogens in water are limite...

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Adenovirus Virion Stability and the Viral Genome: Size Matters

Cited by 56 publications

References 34 publications

Elution Is a Critical Step for Recovering Human Adenovirus 40 from Tap Water and Surface Water by Cross-Flow Ultrafiltration

Elution Is a Critical Step for Recovering Human Adenovirus 40 from Tap Water and Surface Water by Cross-Flow Ultrafiltration

Evaluation of excipients for enhanced thermal stabilization of a human type 5 adenoviral vector through spray drying

Antiviral Properties of Silver Nanoparticles on a Magnetic Hybrid Colloid

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