Virus Inactivation Mechanisms: Impact of Disinfectants on Virus Function and Structural Integrity

Abstract

Oxidative processes are often harnessed as tools for pathogen disinfection. Although the pathways responsible for bacterial inactivation with various biocides are fairly well understood, virus inactivation mechanisms are often contradictory or equivocal. In this study, we provide a quantitative analysis of the total damage incurred by a model virus (bacteriophage MS2) upon inactivation induced by five common virucidal agents (heat, UV, hypochlorous acid, singlet oxygen, and chlorine dioxide). Each treatment targets one or more virus functions to achieve inactivation: UV, singlet oxygen, and hypochlorous acid treatments generally render the genome nonreplicable, whereas chlorine dioxide and heat inhibit host-cell recognition/binding. Using a combination of quantitative analytical tools, we identified unique patterns of molecular level modifications in the virus proteins or genome that lead to the inhibition of these functions and eventually inactivation. UV and chlorine treatments, for example, cause site-specific capsid protein backbone cleavage that inhibits viral genome injection into the host cell. Combined, these results will aid in developing better methods for combating waterborne and foodborne viral pathogens and further our understanding of the adaptive changes viruses undergo in response to natural and anthropogenic stressors.

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

“…4 and Table 1). However, as reported in a previous study (42), not all oxidative protein damage is of biological consequence, as viruses have been found to withstand a large extent of protein oxidation. It is thus not sufficient to quantify the extent of protein degradation to assess its impact on inactivation.…”

Mechanisms of Methods for Hepatitis C Virus Inactivation

“…Even though we did not see an influence of either treatment method on the viral capsid, we cannot exclude that the viral capsid itself might also be damaged since the core ELISA is based on the detection of only a small part of the capsid (27). It has been shown for other viruses that heat inactivation induces structural changes in viral proteins, which might cause the loss of infectivity (29,30) and degrades the viral RNA (31,32). Whether heat inactivation influences only the viral proteins or also the RNA might depend on the applied temperature, as well as on the duration of heat administration.…”

“…UV irradiation, typically at a wavelength of 254 nm, is known to target nucleic acids, while leaving proteins largely preserved (29,33). However, both viral genome and protein damage have been reported previously due to UV irradiation (30,34,35). Viral inactivation by alcohols is thought to be due to membrane damage and rapid protein denaturation (36) and, indeed, HCV RNA integrity was not compromised after treatment of the virus with either ethanol or 2-propanol.…”

Persistence of Infectious Shiga Toxin-Encoding Bacteriophages after Disinfection Treatments

“…The uncertainty regarding these factors makes it difficult to explain the reduction in genome copies observed, but in any case, solar radiation would seem to be the most critical inactivating factor, alone or as a part of a synergistic effect with other factors, affecting either the integrity of the phage capsids and/or the phage DNA. Radiation and oxidation agents have been reported to result in modifications to viral proteins (capsid protein backbone cleavage) and nucleic acids (40). Nevertheless, important variations can be observed depending on the virus assayed, and previous studies in the same mesocosm system with other phages showed similar reduction of infectious phages but almost no reduction when evaluating phage genomes by qPCR (21).…”