UV Radiation Induces Genome‐Mediated, Site‐Specific Cleavage in Viral Proteins

Wigginton, Krista; Menin, Laure; Sigstam, Thérèse; Gannon, Greg; Cascella, M.; Hamidane, Hisham Ben; Tsybin, Yury O.; Waridel, Patrice; Kohn, Tamar

doi:10.1002/cbic.201100601

Cited by 39 publications

(37 citation statements)

References 37 publications

(28 reference statements)

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“…3 and statistical analyses, it is apparent that damage to the nucleic acid is the primary cause of the loss of viral infectivity across the germicidal UV spectrum. Although UV light causes photoproducts or structural modifications in capsid proteins (21), and genome-mediated protein damage has been demonstrated in MS2 (30), this damage does not appear to contribute significantly to a loss of MS2 viral infectivity. In contrast, the spectral sensitivity of adenovirus diverged from the sensitivity of its genome at wavelengths below 240 nm, suggesting that nongenomic damage contributes to UV inactivation at these wavelengths (28).…”

Section: Resultsmentioning

confidence: 99%

“…One explanation as to why there would still be genomic damage from irradiation at wavelengths below 240 nm is the potential for proteins absorbing UV at these wavelengths to transfer energy or extend damage to the RNA. Wigginton et al (30) showed that the presence of viral RNA contributed to site-specific protein damage, suggesting an energy transfer from RNA to viral proteins in MS2 following UV radiation at 253.7 nm. At wavelengths below 240 nm, where protein absorption of UV is highest, it is plausible that the energy transfer would occur in the opposite direction; energy preferentially absorbed by proteins could be generating site-specific RNA damage, resulting in a loss of viral infectivity.…”

Section: Resultsmentioning

confidence: 99%

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Comparison of UV-Induced Inactivation and RNA Damage in MS2 Phage across the Germicidal UV Spectrum

Beck

Rodríguez

Hawkins

et al. 2016

Appl Environ Microbiol

146

123

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c Polychromatic UV irradiation is a common method of pathogen inactivation in the water treatment industry. To improve its disinfection efficacy, more information on the mechanisms of UV inactivation on microorganisms at wavelengths throughout the germicidal UV spectrum, particularly at below 240 nm, is necessary. This work examined UV inactivation of bacteriophage MS2, a common surrogate for enteric pathogens, as a function of wavelength. The bacteriophage was exposed to monochromatic UV irradiation from a tunable laser at wavelengths of between 210 nm and 290 nm. To evaluate the mechanisms of UV inactivation throughout this wavelength range, RT-qPCR (reverse transcription-quantitative PCR) was performed to measure genomic damage for comparison with genomic damage at 253.7 nm. The results indicate that the rates of RNA damage closely mirror the loss of viral infectivity across the germicidal UV spectrum. This demonstrates that genomic damage is the dominant cause of MS2 inactivation from exposure to germicidal UV irradiation. These findings contrast those for adenovirus, for which MS2 is used as a viral surrogate for validating polychromatic UV reactors. UV irradiation is a common method of disinfection in the water treatment industry. UV light induces damage to the genomes of bacteria, protozoa, and viruses, breaking bonds and forming photodimeric lesions in nucleic acids, DNA, and RNA (1, 2). These lesions prevent both transcription and replication and ultimately lead to inactivation of the microorganisms (3, 4). Direct UV damage to nucleic acids occurs at the wavelengths absorbed by DNA and RNA, in the germicidal UV region between 200 and 300 nm (5, 6). In this wavelength range, however, UV light also damages other cellular and viral components, causing, for example, photochemical reactions in proteins and enzymes (7,8). For this reason, UV sources that emit polychromatic light, across the germicidal UV spectrum, are considered more effective at inactivating certain pathogens than sources that emit monochromatic light at 253.7 nm (9-12). As polychromatic sources become more common, more research is being undertaken to understand the mechanisms of inactivation occurring in pathogens exposed to polychromatic UV irradiation.Male-specific (MS2) coliphage is a single-stranded RNA virus. It infects strains of Escherichia coli that produce F ϩ pili, which serve as viral receptors. The virion consists of a short singlestranded RNA genome (3,569 bases) surrounded by an icosahedral protein capsid, 27 nm in diameter (13). MS2 is commonly used in the water treatment industry as a surrogate for enteroviruses because of its similar size, shape, and genome composition (9,14). It serves as a biodosimeter for UV disinfection studies (15) and for UV reactor validation in North America (14, 16). For reactor validation, MS2 is also used as a surrogate for Cryptosporidium and adenovirus, despite the differences in UV sensitivity and spectral sensitivity between these microorganisms. Recent interest has grown regarding microbial ...

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Comparison of UV-Induced Inactivation and RNA Damage in MS2 Phage across the Germicidal UV Spectrum

Beck

Rodríguez

Hawkins

et al. 2016

Appl Environ Microbiol

146

123

View full text Add to dashboard Cite

show abstract

“…7). In previous work (37), it was shown that the degradation of peptide 44 -49 in MS2 was caused by backbone cleavage around amino acids Cys46 and Ser47. This cleavage event was facilitated by the presence of both RNA and cysteine at the cleavage site.…”

Section: Discussionmentioning

confidence: 99%

Subtle Differences in Virus Composition Affect Disinfection Kinetics and Mechanisms

Sigstam

Gannon

Cascella

et al. 2013

Appl Environ Microbiol

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“…These amino acids are responsible for CAR host binding in the fiber knob of HAdV (50). In particular, tyrosine is susceptible to oxidation and degradation by light (25). Thus, indirect solar disinfection may hamper host binding and lower the infectivity of HAdV-2.…”

Section: Mechanisms Contributing To Solar Disinfection Of Adenovirusmentioning

confidence: 99%

“…Susceptible amino acids and peptides located in these structures may play an important role in adenovirus inactivation processes during irradiation with sunlight and UV light. Tyrosine, histidine, and lysine in the fiber head are crucial for host binding in adenovirus (24), and in particular, tyrosine is susceptible to degradation by light (25). Finally, the efficiency of adenovirus inactivation in a setting representative of solar disinfection of drinking water (SODIS), hence exposed to sunlight in a polyethylene terephthalate (PET) bottle, was investigated.…”

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confidence: 99%

Mechanisms of Human Adenovirus Inactivation by Sunlight and UVC Light as Examined by Quantitative PCR and Quantitative Proteomics

Bosshard

Armand

Hamelin

et al. 2013

Appl Environ Microbiol

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Human adenoviruses (HAdV) are important pathogens in both industrialized and developing nations. HAdV has been shown to be relatively resistant to monochromatic UVC light. Polychromatic UVC light, in contrast, is a more effective means of disinfection, presumably due to the involvement of viral proteins in the inactivation mechanism. Solar disinfection of HAdV, finally, is only poorly understood. In this paper, the kinetics and mechanism of HAdV inactivation by UVC light and direct and indirect solar disinfection are elucidated. PCR and mass spectrometry were employed to quantify the extent of genome and protein degradation and to localize the affected regions in the HAdV proteins. For this purpose, we used for the first time an approach involving stable isotope labeling by amino acids in cell culture (SILAC) of a human virus. Inactivation by UVC light and the full sunlight spectrum were found to efficiently inactivate HAdV, whereas UVA-visible light only caused inactivation in the presence of external sensitizers (indirect solar disinfection). Genome damage was significant for UVC but was less important for solar disinfection. In contrast, indirect solar disinfection exhibited extensive protein degradation. In particular, the fiber protein and the amino acids responsible for host binding within the fiber protein were shown to degrade. In addition, the central domain of the penton protein was damaged, which may inhibit interactions with the fiber protein and lead to a disruption of the initial stages of infection. Damage to the hexon protein, however, appeared to affect only regions not directly involved in the infectious cycle.

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UV Radiation Induces Genome‐Mediated, Site‐Specific Cleavage in Viral Proteins

Cited by 39 publications

References 37 publications

Comparison of UV-Induced Inactivation and RNA Damage in MS2 Phage across the Germicidal UV Spectrum

Comparison of UV-Induced Inactivation and RNA Damage in MS2 Phage across the Germicidal UV Spectrum

Subtle Differences in Virus Composition Affect Disinfection Kinetics and Mechanisms

Mechanisms of Human Adenovirus Inactivation by Sunlight and UVC Light as Examined by Quantitative PCR and Quantitative Proteomics

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