Vesicle-Cloaked Enteric Virus Clusters are Environmentally Persistent in Natural and Engineering Water Systems
Open AccessAn individual virion was long believed to act as an independent infectious unit in virology, until the recent discovery of vesicle-cloaked virus clusters which has greatly challenged this central paradigm. Vesicle-cloaked virus clusters (also known as viral vesicles) are phospholipid-bilayer encapsulated fluid sacs that contain multiple virions or multiple copies of viral genomes. Human enteric viruses transmitting through the fecal-oral route are leading causes for worldwide waterborne diseases and they are great burden for public health and economy, while norovirus and rotavirus are the most common enteric viruses. The reported prevalence of vesicle-cloaked enteric virus clusters in stool has raised concerns whether the current disinfection, sanitation, and hygiene practices can effectively control environmental pollution by these emerging pathogenic units. This dissertation focuses on the persistence of enteric virus vesicles in natural and wastewater, as well as their resistance to disinfection strategies. The first part of this dissertation aims to investigate the persistence and resistance of cell-culture-derived murine norovirus (MNV-1) vesicles to UV254 disinfection. My results showed MNV-1 vesicles with high persistence under temperature variation (i.e., freeze-thaw) and they were partially resistant to detergent decomposition. MNV-1 vesicles were 1.89-3.17-fold more infectious in vitro than their free virus counterparts. Most importantly, MNV-1 vesicles were up to 2.16-times more resistant to UV254 disinfection than free MNV-1 at a low viral load in vitro. Interestingly, with the increase of the viral load, free MNV-1 and MNV-1 vesicles showed equivalent resistance to UV254 disinfection. The increased multiplicity of infection provided by vesicles is in part responsible for these attributes. The second part of this dissertation aims to investigate the persistence of rotavirus vesicles in wastewater and fresh water, as well as their resistance to disinfections including free chlorine and UV254 using an in vivo model. My results showed that murine rotavirus vesicles did not decompose in both freshwater and wastewater at the room temperature for up to 7 days. Their infectivity to mouse pups, including virus shedding in stool and virus replication in small intestines, was statistically the same before and after incubating in the wastewater. 23.6-26.6% of murine rotavirus vesicles remained intact even after 16-week-incubation in freshwater and wastewater at the room temperature, highlighting the viral vesicles are highly persistent in aquatic environments. Murine rotavirus vesicles are also resistant to free chlorine and UV254 disinfection. Particularly, the vesicles maintained their integrity after exposure to free chlorine of 13.3 mg min L-1, and their infectivity was similar before and after chlorination. In contrast, free rotaviruses were generally less infectious than the rotavirus vesicles regardless of chlorination, and chlorination reduced virus shedding in the stool by 2.22- and 6.39-fold for the rotavirus vesicles and free rotaviruses, respectively. En bloc transmission through the viral vesicles could be responsible to vesicles’ resistance to disinfection, due to an increased multiplicity of infection and/or complementary and cooperative interactions among virions to promote infection. The last part of this dissertation aims to provide a review of the perspectives that extend from the interaction between human pathogenic viruses when viral vesicles are formed to all interactions between human pathogenic viruses and their microbial neighbors, including amoeba, bacteria, and viruses. The interactions of the human pathogenic viruses with their microbial neighbors enhance the persistence and infectivity of the viruses, because the viruses can dodge the inactivation by environmental stresses and disinfectants by hiding inside their neighbors, they can gather with their neighbors to increase the multiplicity of infection (MOI) and genetic recombination and reassortment, and they can also evade the immune systems of the hosts. This dissertation, for the first time, sheds light on the environmental behavior of vesicle-cloaked enteric virus clusters as unique emerging pathogenic units, which blur the distinction between non-enveloped and enveloped viruses but behave like neither of them by showing higher persistence in both natural and engineering water systems. This dissertation emphasizes the importance of selecting appropriate surrogates and animal models in the investigations on the persistence and disinfection of human pathogenic viruses. This dissertation also highlights the impact of the social life of human pathogenic viruses on the environmental and biological behavior of the viruses, and guide engineering design and regulations for developing reliable and robust disinfection and sanitation practices to protect public health.
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