Inactivation of RNA Viruses by Gamma Irradiation: A Study on Mitigating Factors

Abstract

Effective inactivation of biosafety level 4 (BSL-4) pathogens is vital in order to study these agents safely. Gamma irradiation is a commonly used method for the inactivation of BSL-4 viruses, which among other advantages, facilitates the study of inactivated yet morphologically intact virions. The reported values for susceptibility of viruses to inactivation by gamma irradiation are sometimes inconsistent, likely due to differences in experimental protocols. We analyzed the effects of common sample attributes on the inactivation of a recombinant vesicular stomatitis virus expressing the Zaire ebolavirus glycoprotein and green fluorescent protein. Using this surrogate virus, we found that sample volume and protein content of the sample modulated viral inactivation by gamma irradiation but that air volume within the sample container and the addition of external disinfectant surrounding the sample did not. These data identify several factors which alter viral susceptibility to inactivation and highlight the usefulness of lower biosafety level surrogate viruses for such studies. Our results underscore the need to validate inactivation protocols of BSL-4 pathogens using “worst-case scenario” procedures to ensure complete sample inactivation.

Infection Load and Prevalence of Novel Viruses Identified from the Bank Vole Do Not Associate with Exposure to Environmental Radioactivity

“…The effects of environmental radiation on host-viral dynamics in natural systems are unknown. While high doses (in excess of several kilograys, kGy) of ionizing radiation inactivate viruses [19,20], exposure to lower doses (2.5-25 Gy) can activate replication in some viruses, such as cytomegalovirus [21], endogenous retroviruses [22], human immunodeficiency virus [23], hepatitis B virus [24,25], Epstein-Barr virus [26,27], reovirus [28], herpes simplex virus [29], parvoviruses [30,31], and poliovirus [32]. Virus activation by irradiation may be facilitated by radiation-mediated immunosuppression that makes the host more susceptible to virus infection and replication [33][34][35], or by radiation-induced activation of the DNA repair proteins that some viruses utilize in their replication [36,37].…”

Gamma Irradiation as an Effective Method for Inactivation of Emerging Viral Pathogens

“…Multiple methods can be applied following approved safety testing by institutional and national authorities including those based on chemical, heat, and radiation treatment. [1][2][3][4][5][6][7] Gamma irradiation, mainly using a cobalt-60 source, is an established and commonly used method in the biocontainment field. This inactivation method is preferred for specimens that are used for, but not limited to, a variety of serological, broader immunological, and biochemical assays for which structural integrity of proteins and particles is of certain importance.…”

“…The absorbed dose of gamma irradiation is affected by multiple factors such as sample origin, sample composition, sample volume, irradiation temperature, distance to irradiation source, and others. 6 The main viral inactivation mechanism is thought to be the destruction of replication-competent nucleic acid either directly by radiolytic cleavage or cross-linking of genetic material or indirectly by the action of radicals on nucleic acids and, to a lesser degree, proteins. 6,13,14 According to regulations, process validation for a select agent can be performed with a representative virus family member as a surrogate.…”

“…6 The main viral inactivation mechanism is thought to be the destruction of replication-competent nucleic acid either directly by radiolytic cleavage or cross-linking of genetic material or indirectly by the action of radicals on nucleic acids and, to a lesser degree, proteins. 6,13,14 According to regulations, process validation for a select agent can be performed with a representative virus family member as a surrogate. Here, we tested inactivation through gamma irradiation of selected representative emerging/reemerging viral pathogens in a liquid medium containing protein, one of the most common sample sources for irradiation inactivation in biocontainment operation.…”

Type of the Paper: Article Homogenous Gamma-Irradiation by a Linear Accelerator for Inactivation of viruses in Plasma Samples, a Pilot Study with HIV-1-Infected Plasma

“…However, phase III trials are running for Mirasol® and INTERCEPT® with RBCs, using ribo avin/UVB and a frangible anchor linker effector, respectively. [1] γ-irradiation has been demonstrated to be able to inactivate viruses [4][5][6][7][8][9][10][11] and is routinely used for decontaminating tissue allografts. [6,7,11] However, γ-irradiation is known to damage RBCs, as well.…”