Mengyang Zhang - Vesicle-cloaked Virus Clusters

Vesicle-cloaked Virus Clusters

Vesicle-cloaked virus clusters (or viral vesicles) are emerging pathogenic units distinct from both enveloped and non-enveloped viruses, and they are phospholipid-bilayer-encapsulated extracellular vesicles (EVs) containing multiple virions or multiple copies of naked viral genomes. Viral egress and transmission have long been described to take place through single free virus particles. However, viruses can also shed into the environment and transmit as populations clustered inside extracellular vesicles (EVs), a process we had first called vesicle-mediated en bloc transmission. The discovery of viral vesicles greatly challenges the central paradigm of viral transmission and infection as a single virion. A broad spectrum of enveloped and non-enveloped viruses, especially enteric viruses like poliovirus, coxsackievirus, norovirus, and rotavirus, have been found to be present as viral vesicles in their lifecycle from egressing from host cells to spreading and then infecting the next host. Viral vesicles can deliver from 1 to 5 to more than 25 virions to a host cell at the same time, and the vesicle size ranges from 50 to 100 nm to several hundred nanometers, depending on the virus type and the cellular organelles viral vesicles originate from, including plasma membranes, autophagosomes, and multivesicular bodies.

Viral vesicles are environmentally and biologically important because they are ubiquitously present in feces (contributing up to ∼50% of the total virus population) that can contaminate the environment. I investigated the environmental persistence of enteric virus vesicles in both natural and engineering water systems. My research showed that they are highly persistent in natural and wastewater, as well as under diverse environmental stressors. Enteric virus vesicles are more infectious and more resistant to disinfection strategies compared to their counterparts of free viruses. Viral vesicles not only increase clinical burden but also promote environmental transmission of viral pathogens and eventually pose a higher risk to public health when compared to free viruses.

Emerging Pathogenic Unit of Vesicle-Cloaked Murine Norovirus Clusters is Resistant to Environmental Stresses and UV254 Disinfection

Norovirus is a global leading causative agent of gastroenteritis, and the reported prevalence of vesicle-cloaked norovirus clusters in stool has raised concerns whether the current disinfection, sanitation, and hygiene practices can effectively control environmental pollution by these pathogenic units. In this study, we have demonstrated that vesicle-cloaked murine norovirus (MNV-1) clusters were highly persistent 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. We show that the increased multiplicity of infection provided by vesicles is in part responsible for these attributes. Our study, for the first time, sheds light on the environmental behavior of vesicle-cloaked virus clusters as unique emerging pathogenic units. Our study highlights the need to revisit current paradigms of disinfection, sanitation, and hygiene practices for protecting public health.

Publication: Emerging Pathogenic Unit of Vesicle-Cloaked Murine Norovirus Clusters is Resistant to Environmental Stresses and UV254 Disinfection

Collaborators: Kim Y. Green, National Institute of Allergy and Infectious Diseases, National Institutes of Health

Christopher K. E. Bleck, Electron Microcopy Core, National Institutes of Health

Vesicle-Cloaked Rotavirus Clusters are Environmentally Persistent and Resistant to Free Chlorine Disinfection

Norovirus is a global leading causative agent of gastroenteritis, and the reported prevalence of vesicle-cloaked norovirus clusters in stool has raised concerns whether the current disinfection, sanitation, and hygiene practices can effectively control environmental pollution by these pathogenic units. In this study, we have demonstrated that vesicle-cloaked murine norovirus (MNV-1) clusters were highly persistent 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. We show that the increased multiplicity of infection provided by vesicles is in part responsible for these attributes. Our study, for the first time, sheds light on the environmental behavior of vesicle-cloaked virus clusters as unique emerging pathogenic units. Our study highlights the need to revisit current paradigms of disinfection, sanitation, and hygiene practices for protecting public health.

Publication: Vesicle-Cloaked Rotavirus Clusters are Environmentally Persistent and Resistant to Free Chlorine Disinfection