RESUMEN
Large scale outbreaks of infectious respiratory disease have repeatedly plagued the globe over the last 100 years. The scope and strength of the outbreaks are getting worse as pathogenic RNA viruses are rapidly evolving and highly evasive to vaccines and anti-viral drugs. Germicidal UV-C is considered as a robust agent to disinfect RNA viruses regardless of their evolution. While genomic damage by UV-C has been known to be associated with viral inactivation, the precise relationship between the damage and inactivation remains unsettled as genomic damage has been analyzed in small areas, typically under 0.5 kb. In this study, we assessed genomic damage by the reduced efficiency of reverse transcription of regions of up to 7.2 kb. Our data seem to indicate that genomic damage was directly proportional to the size of the genome, and a single hit of damage was sufficient for inactivation of RNA viruses. The high efficacy of UV-C is already effectively adopted to inactivate airborne RNA viruses.
Asunto(s)
Virus ARN , Rayos Ultravioleta , Inactivación de Virus , Virus ARN/efectos de la radiación , Virus ARN/genética , Virus ARN/fisiología , Inactivación de Virus/efectos de la radiación , Genoma Viral , Humanos , Transcripción Reversa , ARN Viral/genéticaRESUMEN
In the event of an unpredictable viral outbreak requiring high/maximum biosafety containment facilities (i.e. BSL3 and BSL4), X-ray irradiation has the potential to relieve pressures on conventional diagnostic bottlenecks and expediate work at lower containment. Guided by Monte Carlo modelling and in vitro 1-log10 decimal-reduction value (D-value) predictions, the X-ray photon energies required for the effective inactivation of zoonotic viruses belonging to the medically important families of Flaviviridae, Nairoviridae, Phenuiviridae and Togaviridae are demonstrated. Specifically, it is shown that an optimized irradiation approach is attractive for use in a multitude of downstream detection and functional assays, as it preserves key biochemical and immunological properties. This study provides evidence that X-ray irradiation can support emergency preparedness, outbreak response and front-line diagnostics in a safe, reproducible and scalable manner pertinent to operations that are otherwise restricted to higher containment BSL3 or BSL4 laboratories.
Asunto(s)
Virus ARN/fisiología , ARN Viral/genética , Inactivación de Virus , Rayos X/efectos adversos , Animales , Chlorocebus aethiops , Defensa Civil , Contención de Riesgos Biológicos , Células Nutrientes , Humanos , Método de Montecarlo , Nairovirus/fisiología , Nairovirus/efectos de la radiación , Virus ARN/efectos de la radiación , ARN Viral/efectos de la radiación , Análisis de Secuencia de ARN , Togaviridae/fisiología , Togaviridae/efectos de la radiación , Células Vero , Zoonosis Virales/prevención & control , Virus Zika/fisiología , Virus Zika/efectos de la radiaciónRESUMEN
BACKGROUND: Arboviruses, including dengue (DENV 1-4), chikungunya (CHIKV), and Ross River (RRV), are emerging viruses that are a risk for transfusion safety globally. An approach for managing this risk is pathogen inactivation, such as the THERAFLEX UV-Platelets system. We investigated the ability of this system to inactivate the above mentioned arboviruses. STUDY DESIGN AND METHODS: DENV 1-4, CHIKV, or RRV were spiked into buffy coat (BC)-derived platelet (PLT) concentrates in additive solution and treated with the THERAFLEX UV-Platelets system at the following doses: 0.05, 0.1, 0.15, and 0.2 J/cm(2) (standard dose). Pre- and posttreatment samples were taken for each dose, and the level of viral infectivity was determined. RESULTS: At the standard ultraviolet C (UVC) dose (0.2 J/cm(2) ), viral inactivation of at least 4.43, 6.34, and 5.13 log or more, was observed for DENV 1-4, CHIKV, and RRV, respectively. A dose dependency in viral inactivation was observed with increasing UVC doses. CONCLUSIONS: Our study has shown that DENV, CHIKV, and RRV, spiked into BC-derived PLT concentrates, were inactivated by the THERAFLEX UV-Platelets system to the limit of detection of our assay, suggesting that this system could contribute to the safety of PLT concentrates with respect to these emerging arboviruses.
Asunto(s)
Plaquetas/virología , Transfusión de Plaquetas/normas , Virus ARN/efectos de la radiación , Rayos Ultravioleta , Inactivación de Virus/efectos de la radiación , Seguridad de la Sangre/métodos , Virus Chikungunya/efectos de la radiación , Virus del Dengue/efectos de la radiación , Relación Dosis-Respuesta en la Radiación , Humanos , Límite de Detección , Transfusión de Plaquetas/efectos adversos , Virus del Río Ross/efectos de la radiaciónRESUMEN
Pancreatin is a substance containing enzymes, principally amylase, lipase, and protease. It is obtained from bovine or porcine pancreas and used in the treatment of pancreatic endocrine insufficiency in humans. Regulations and safety concerns mandate viral clearance (virus removal or inactivation) in biopharmaceuticals such as pancreatin. A virus validation study was performed to evaluate virus clearance achieved in the final step of drying under vacuum by testing a panel of four animal viruses: Pseudorabies virus (PRV), Encephalomyocarditis virus (EMCV), Bovine viral diarrhea virus (BVDV), and Porcine parvovirus (PPV). Because of the product's virucidal effect and high cytotoxicity, the starting material was diluted to a ratio of 0.67 g of dried pancreatin resuspended in 13.5 mL of cell culture medium followed by a 50-fold dilution in cell culture medium before spiking. After heating at 60±1°C for 5 h, the samples were diluted about 5-fold in cell culture medium and titered by the plaque assay method. The virus reduction factor ranged from 5.59 (for PPV) to 7.07 (for EMCV) and no viral plaque was observed, indicating that the process step was effective in the reduction and removal of virus contamination. Though no virus contamination events in pancreatin have been reported to date, evaluation of the production process for its ability to inactivate and/or remove virus contamination, particularly from zoonotic viral agents such as hepatitis E virus and Norovirus considered emerging pathogens, is necessary to ensure the viral safety of animal-derived biopharmaceuticals.
Asunto(s)
Virus ADN/aislamiento & purificación , Desinfección/métodos , Pancreatina , Virus ARN/aislamiento & purificación , Tecnología Farmacéutica/métodos , Inactivación de Virus , Animales , Bovinos , Virus ADN/fisiología , Virus ADN/efectos de la radiación , Calor , Virus ARN/fisiología , Virus ARN/efectos de la radiación , Porcinos , Temperatura , Factores de Tiempo , Carga Viral , Ensayo de Placa ViralRESUMEN
BACKGROUND: Birnaviruses form a distinct family of double-stranded RNA viruses infecting animals as different as vertebrates, mollusks, insects and rotifers. With such a wide host range, they constitute a good model for studying the adaptation to the host. Additionally, several lines of evidence link birnaviruses to positive strand RNA viruses and suggest that phylogenetic analyses may provide clues about transition. RESULTS: We characterized the genome of a birnavirus from the rotifer Branchionus plicalitis. We used X-ray structures of RNA-dependent RNA polymerases and capsid proteins to obtain multiple structure alignments that allowed us to obtain reliable multiple sequence alignments and we employed "advanced" phylogenetic methods to study the evolutionary relationships between some positive strand and double-stranded RNA viruses. We showed that the rotifer birnavirus genome exhibited an organization remarkably similar to other birnaviruses. As this host was phylogenetically very distant from the other known species targeted by birnaviruses, we revisited the evolutionary pathways within the Birnaviridae family using phylogenetic reconstruction methods. We also applied a number of phylogenetic approaches based on structurally conserved domains/regions of the capsid and RNA-dependent RNA polymerase proteins to study the evolutionary relationships between birnaviruses, other double-stranded RNA viruses and positive strand RNA viruses. CONCLUSIONS: We show that there is a good correlation between the phylogeny of the birnaviruses and that of their hosts at the phylum level using the RNA-dependent RNA polymerase (genomic segment B) on the one hand and a concatenation of the capsid protein, protease and ribonucleoprotein (genomic segment A) on the other hand. This correlation tends to vanish within phyla. The use of advanced phylogenetic methods and robust structure-based multiple sequence alignments allowed us to obtain a more accurate picture (in terms of probability of the tree topologies) of the evolutionary affinities between double-stranded RNA and positive strand RNA viruses. In particular, we were able to show that there exists a good statistical support for the claims that dsRNA viruses are not monophyletic and that viruses with permuted RdRps belong to a common evolution lineage as previously proposed by other groups. We also propose a tree topology with a good statistical support describing the evolutionary relationships between the Picornaviridae, Caliciviridae, Flaviviridae families and a group including the Alphatetraviridae, Nodaviridae, Permutotretraviridae, Birnaviridae, and Cystoviridae families.
Asunto(s)
Evolución Molecular , Virus ARN/genética , Rotíferos/virología , Secuencia de Aminoácidos , Animales , Genoma Viral , Especificidad del Huésped , Filogenia , Virus ARN/clasificación , Virus ARN/fisiología , Virus ARN/efectos de la radiación , ARN Bicatenario/genética , Rotíferos/clasificación , Alineación de Secuencia , Proteínas Virales/química , Proteínas Virales/genéticaRESUMEN
The comparative susceptibility of DNA- and RNA-type viruses to photodynamic inactivation has not yet been clearly addressed. In this study the effect of the tricationic porphyrin Tri-Py(+)-Me-PF on the inactivation of four DNA and three RNA non-enveloped phages was compared. The results obtained show that the photodynamic efficiency varied with the phage type, the RNA-type phages being much more easily photoinactivated than the DNA-type ones.
Asunto(s)
Bacteriófagos/fisiología , Virus ADN/fisiología , Fotólisis , Fármacos Fotosensibilizantes/farmacología , Porfirinas/farmacología , Virus ARN/fisiología , Bacterias/virología , Bacteriófagos/efectos de los fármacos , Bacteriófagos/efectos de la radiación , Virus ADN/efectos de los fármacos , Virus ADN/efectos de la radiación , Dimetilsulfóxido/química , Luz , Espectroscopía de Resonancia Magnética , Fármacos Fotosensibilizantes/síntesis química , Porfirinas/síntesis química , Virus ARN/efectos de los fármacos , Virus ARN/efectos de la radiación , Especificidad de la EspecieRESUMEN
Human tissue allografts are widely used in a variety of clinical applications with over 1.5 million implants annually in the US alone. Since the 1990s, most clinically available allografts have been disinfected to minimize risk of disease transmission. Additional safety assurance can be provided by terminal sterilization using low dose gamma irradiation. The impact of such irradiation processing at low temperatures on viruses was the subject of this study. In particular, both human tendon and cortical bone samples were seeded with a designed array of viruses and the ability of gamma irradiation to inactivate those viruses was tested. The irradiation exposures for the samples packed in dry ice were 11.6-12.9 kGy for tendon and 11.6-12.3 kGy for bone, respectively. The viruses, virus types, and log reductions on seeded tendon and bone tissue, respectively, were as follows: Human Immunodeficiency Virus (RNA, enveloped), >2.90 and >3.20; Porcine Parvovirus (DNA, non-enveloped), 1.90 and 1.58; Pseudorabies Virus (DNA, enveloped), 3.80 and 3.79; Bovine Viral Diarrhea Virus (RNA, enveloped), 2.57 and 4.56; and Hepatitis A Virus (RNA, non-enveloped), 2.54 and 2.49, respectively. While proper donor screening, aseptic technique, and current disinfection practices all help reduce the risk of viral transmission from human allograft tissues, data presented here indicate that terminal sterilization using a low temperature, low dose gamma irradiation process inactivates both enveloped and non-enveloped viruses containing either DNA or RNA, thus providing additional assurance of safety from viral transmission.
Asunto(s)
Virus ADN/efectos de la radiación , Rayos gamma , Virus ARN/efectos de la radiación , Esterilización/métodos , Inactivación de Virus , Trasplante Óseo , Huesos/efectos de la radiación , Huesos/virología , Línea Celular , Humanos , Tendones/efectos de la radiación , Tendones/virologíaRESUMEN
A method was developed for discriminating damaged viruses or naked viral RNA from intact viruses by ethidium monoazide (EMA) treatment before RT-PCR. The applied EMA treatment consisted of three steps: (1) EMA dose, (2) exposure to light, and (3) additional purification by spin-column gel filtration. Approximately 4-log reduction in viral RNA concentration was observed by adding a dose of 10 µg/mL-EMA with 300 s of light irradiation. Although residual EMA can be an inhibitor of RT-PCR, its effect was reduced by spin-column gel filtration or a QIAamp® Viral RNA Mini Kit. EMA-RT-PCR was applied to the thermally treated PV1. Results of EMA-RT-PCR were similar to the plaque assay when PV1 was thermally inactivated. Although this is a preliminary study investigating applicability of the EMA-RT-PCR method for RNA viruses, the results suggest that the method is potentially applicable for the selective detection of epidemiologically important enteric viruses in water such as enteroviruses and noroviruses.
Asunto(s)
Azidas/farmacología , Calor , Virus ARN/efectos de los fármacos , ARN Viral/aislamiento & purificación , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Animales , Luz , Ratones , Norovirus/efectos de los fármacos , Norovirus/genética , Norovirus/aislamiento & purificación , Norovirus/efectos de la radiación , Virus ARN/genética , Virus ARN/aislamiento & purificación , Virus ARN/efectos de la radiación , ARN Viral/genéticaRESUMEN
AIM: To explore whether ultraviolet (UV) light treatment within a closed circulating and filtered water drainage system can kill plant pathogenic species. METHODS AND RESULTS: Ultraviolet experiments at 254 nm were conducted to determine the inactivation coefficients for seven plant pathogenic species. At 200 mJ cm(-2), the individual species log reductions obtained for six Ascomycete fungi and a cereal virus were as follows: Leptosphaeria maculans (9·9-log), Leptosphaeria biglobosa (7·1-log), Barley stripe mosaic virus (BSMV) (4·1-log), Mycosphaerella graminicola (2·9-log), Fusarium culmorum (1·2-log), Fusarium graminearum (0·6-log) and Magnaporthe oryzae (0·3-log). Dilution experiments showed that BSMV was rendered noninfectious when diluted to >1/512. Follow-up large-scale experiments using up to 400 l of microbiologically contaminated waste water revealed that the filtration of drainage water followed by UV treatment could successfully be used to inactivate several plant pathogens. CONCLUSIONS: By combining sedimentation, filtration and UV irradiation within a closed system, plant pathogens can be successfully removed from collected drainage water. SIGNIFICANCE AND IMPACT OF THE STUDY: Ultraviolet irradiation is a relatively low cost, energy efficient and labour nonintensive method to decontaminate water arising from a suite of higher biological containment level laboratories and plant growth rooms where genetically modified and/or quarantine fungal and viral plant pathogenic organisms are being used for research purposes.
Asunto(s)
Agricultura/métodos , Ascomicetos/efectos de la radiación , Virus ARN/efectos de la radiación , Rayos Ultravioleta , Microbiología del Agua , Purificación del Agua/métodos , Descontaminación , Filtración , Microscopía Electrónica de Transmisión , Plantas/virología , Virus ARN/ultraestructura , Inactivación de Virus/efectos de la radiaciónRESUMEN
The mechanism of bacteriophage photoinactivation by methylene blue and light (MB+L) involves genomic RNA damage. In this study, two RNA viruses, Sindbis virus (SINV) and hepatitis C virus were treated by MB+L and their nucleic acids were amplified to show that RNA lesions occurred during inactivation. During MB+L inactivation, the viral load of both viruses was significantly reduced as MB+L exposure increased. The nucleic acid amplification of treated viral RNA was inhibited in a time-dependent manner and the percentage inhibition of amplification reached about 99% after 30 min of treatment. Furthermore, as compared to SINV viral infectivity detected by quantification of the 50% tissue culture infective dose (TCID(50)), the inhibition of SINV RNA amplification strongly correlated with a decrease in in vitro infectivity (R(2) > 0.94), suggesting that RNA serves as the main target during MB+L inactivation.
Asunto(s)
Luz , Azul de Metileno/farmacología , Ácidos Nucleicos/química , Virus ARN/efectos de los fármacos , Virus ARN/efectos de la radiación , Animales , Antivirales/farmacología , Células Cultivadas , Cricetinae , Ácidos Nucleicos/genética , Reacción en Cadena de la Polimerasa , Infecciones por Virus ARN/virologíaRESUMEN
Robustness describes the capacity for a biological system to remain canalized despite perturbation. Genetic robustness affords maintenance of phenotype despite mutational input, necessarily involving the role of epistasis. Environmental robustness is phenotypic constancy in the face of environmental variation, where epistasis may be uninvolved. Here we discuss genetic and environmental robustness, from the standpoint of infectious disease evolution, and suggest that robustness may be a unifying principle for understanding how different disease agents evolve. We focus especially on viruses with RNA genomes due to their importance in the evolution of emerging diseases and as model systems to test robustness theory. We present new data on adaptive constraints for a model RNA virus challenged to evolve in response to UV radiation. We also draw attention to other infectious disease systems where robustness theory may prove useful for bridging evolutionary biology and biomedicine, especially the evolution of antibiotic resistance in bacteria, immune evasion by influenza, and malaria parasite infections.
Asunto(s)
Evolución Biológica , Enfermedades Transmisibles/genética , Modelos Genéticos , Bacteriófago phi 6/genética , Brotes de Enfermedades , Farmacorresistencia Bacteriana/genética , Ambiente , Humanos , Malaria/parasitología , Mutación , Dinámicas no Lineales , Virus ARN/genética , Virus ARN/efectos de la radiación , Rayos UltravioletaRESUMEN
UV radiation from the sun is the primary germicide in the environment. The goal of this study was to estimate inactivation of viruses by solar exposure. We reviewed published reports on 254-nm UV inactivation and tabulated the sensitivities of a wide variety of viruses, including those with double-stranded DNA, single-stranded DNA, double-stranded RNA, or single-stranded RNA genomes. We calculated D(37) values (fluence producing on average one lethal hit per virion and reducing viable virus to 37%) from all available data. We defined "size-normalized sensitivity" (SnS) by multiplying UV(254) sensitivities (D(37) values) by the genome size, and SnS values were relatively constant for viruses with similar genetic composition. In addition, SnS values were similar for complete virions and their defective particles, even when the corresponding D(37) values were significantly different. We used SnS to estimate the UV(254) sensitivities of viruses for which the genome composition and size were known but no UV inactivation data were available, including smallpox virus, Ebola, Marburg, Crimean-Congo, Junin, and other hemorrhagic viruses, and Venezuelan equine encephalitis and other encephalitis viruses. We compiled available data on virus inactivation as a function of wavelength and calculated a composite action spectrum that allowed extrapolation from the 254-nm data to solar UV. We combined our estimates of virus sensitivity with solar measurements at different geographical locations to predict virus inactivation. Our predictions agreed with the available experimental data. This work should be a useful step to understanding and eventually predicting the survival of viruses after their release in the environment.
Asunto(s)
Virus ADN/efectos de la radiación , Virus ARN/efectos de la radiación , Luz Solar , Radiación Cósmica , Virus ADN/clasificación , Genoma Viral , Geografía , Virus ARN/clasificación , ARN Bicatenario/efectos de la radiación , ARN Viral/efectos de la radiación , Actividad Solar , Rayos Ultravioleta , Estados UnidosAsunto(s)
Antivirales/sangre , Virus ADN/crecimiento & desarrollo , Azul de Metileno/farmacología , Fármacos Fotosensibilizantes/farmacología , Virus ARN/crecimiento & desarrollo , Activación Viral/fisiología , Virus ADN/efectos de los fármacos , Virus ADN/efectos de la radiación , Humanos , Luz , Fotoquimioterapia/instrumentación , Fotoquimioterapia/métodos , Plasmaféresis/métodos , Virus ARN/efectos de los fármacos , Virus ARN/efectos de la radiación , Activación Viral/efectos de los fármacos , Activación Viral/efectos de la radiaciónRESUMEN
By using poly(A)-selected RNA from Berne virus (BEV)-infected embryonic mule skin cells as a template, cDNA was prepared and cloned in plasmid pUC9. Recombinants covering a contiguous sequence of about 10 kilobases were identified. Northern (RNA) blot hybridizations with various restriction fragments from these clones showed that the five BEV mRNAs formed a 3'-coterminal nested set. Sequence analysis revealed the presence of four complete open reading frames of 4743, 699, 426, and 480 nucleotides, with initiation codons coinciding with the 5' ends of BEV RNAs 2 through 5, respectively. By using primer extension analysis and oligonucleotide hybridizations, RNA 5 was found to be contiguous on the consensus sequence. The transcription of BEV mRNAs was studied by means of UV mapping. BEV RNAs 1, 2, and 3 were shown to be transcribed independently, which is also likely--although not rigorously proven--for RNAs 4 and 5. Upstream of the AUG codon of each open reading frame a conserved sequence pattern was observed which is postulated to function as a core promoter sequence in subgenomic RNA transcription. In the area surrounding the core promoter region of the two most abundant subgenomic BEV RNAs, a number of homologous sequence motifs were identified.
Asunto(s)
Virus ARN/genética , ARN Mensajero/genética , Transcripción Genética , Replicación Viral , Animales , Secuencia de Bases , Línea Celular , Clonación Molecular , Datos de Secuencia Molecular , Hibridación de Ácido Nucleico , Regiones Promotoras Genéticas , Sondas ARN , Virus ARN/fisiología , Virus ARN/efectos de la radiación , Mapeo Restrictivo , Transcripción Genética/efectos de la radiación , Rayos UltravioletaRESUMEN
Eight commonly used chemical disinfectants and physical treatments (UV irradiation and heating) were applied to both enveloped RNA viruses (Sendai virus, canine distemper virus) and unenveloped RNA viruses (Theiler's murine encephalomyelitis virus, reo virus type 3) to inactivate infectious virus particles. According to the results, alcohols (70% ethanol, 50% isopropanol), formaldehyde (2% formalin), halogen compounds (52ppm iodophor, 100ppm sodium hypochlorite), quaternary ammonium chloride (0.05% benzalkonium chloride) and 1% saponated cresol showed virucidal effects giving more than 99.95% reduction in the infectivity of virus samples of Sendai virus and canine distemper after 10 minutes exposure. There was no significant difference in the effects on the two enveloped RNA viruses. The susceptibility of unenveloped RNA viruses to chemical disinfectants and physical treatments differed greatly from the enveloped viruses. The two unenveloped viruses showed distinct resistance to 50% isopropanol, 2% formalin, 1% saponated cresol and to physical treatments (heating at 45, 56, 60 degrees C, and UV irradiation). These results indicate that using physicochemical methods to inactivate RNA viruses in laboratory animal facilities should be considered in accordance with the characteristics of the target virus. For practical purposes in disinfecting enveloped RNA viruses, 70% ethanol, 0.05% quaternary ammonium chloride and 1% saponated cresol diluted in hot water (greater than 60 degrees C) are considered as effective as UV irradiation. For unenveloped RNA viruses, halogen compounds, more than 1,000 ppm sodium hypochlorite or 260 ppm iodophor are recommended over a period of 10 minutes for disinfecting particles, although these compounds result in an oxidation problem with many metals.
Asunto(s)
Animales de Laboratorio/microbiología , Desinfección , Virus ARN/efectos de los fármacos , Esterilización , Animales , Desinfectantes/farmacología , Calor , Virus ARN/efectos de la radiación , Rayos UltravioletaRESUMEN
Thermal inactivation of Berne virus proceeded at a linear rate between 31 degrees and 43 degrees C. Storage at temperatures lower than -20 degrees C preserved the infectivity, while at 4 degrees C appreciable loss occurred between 92 and 185 days. Freeze-drying or desiccation at 22 degrees C caused only insignificant loss of infectivity. Virus preparations were not affected by pH values between 2.5 and 10.3. Inactivation by UV occurred more rapidly than with herpes, toga and rhabdoviruses. Berne virus infectivity was sensitive to pronase and B. subtilis proteinase. It was not inactivated by trypsin and chymotrypsin treatment, which resulted in enhancement of infectivity; low concentrations of pronase (less than 10 micrograms ml-1) had a similar effect on Berne virus. Neither phospholipase C or RNase, alone or in combination, nor sodium deoxycholate (0.1%) inactivated the virus; in contrast, Triton X-100 (0.1%; 1.0%) caused rapid inactivation with a constant level of residual infectivity.
Asunto(s)
Virus ARN/crecimiento & desarrollo , Animales , Línea Celular , Ácido Desoxicólico/farmacología , Detergentes/farmacología , Farmacorresistencia Microbiana , Grabado por Congelación , Caballos , Octoxinol , Péptido Hidrolasas/farmacología , Polietilenglicoles/farmacología , Virus ARN/efectos de los fármacos , Virus ARN/efectos de la radiación , Ribonucleasas/farmacología , Temperatura , Fosfolipasas de Tipo C/farmacología , Rayos UltravioletaRESUMEN
The virions of all known viruses are composed of small amounts of genomic nucleic acid enveloped by proteins and other macromolecules. The aetiological agents of scrapie disease and the other subacute spongiform virus encephalopathies (SSVE), a group of slow, fatal degenerative diseases of the central nervous system, are, based on their resistance to sterilization and on indirect measurements suggesting subviral size, thought to have non-viral structures (see refs 1-3 for reviews). The kinetic studies reported here demonstrate that scrapie's resistance to many inactivants is limited to small subpopulations of the total infectivity, the majority population being highly sensitive to inactivation. Moreover, control inactivations of conventional viruses provide examples of both scrapie-like resistant subpopulations and complete insensitivity to virucidal agents, especially when those viruses, like scrapie, are suspended in hamster brain homogenate. Virus controls further establish that the ability of the scrapie agent to penetrate dilute agarose-acrylamide electrophoretic gels is shared by conventional viruses. Direct comparison of scrapie's resistance to ionizing radiation with the resistances of other viruses places scrapie with the smaller viruses, as opposed to requiring a subviral size as claimed.