title: Silicon Dioxide Impedes Antiviral Response and Causes Genotoxic Insult During Calicivirus Replication.
abstract: Noroviruses (NoV) are the leading cause of nonbacterial gastroenteritis in humans, and replicate extensively in the human gastrointestinal (GI) tract. Silica (also known as silicon dioxide, SiO2) nanoparticles (NPs) used in processed foods, dairy products, and beverages also accumulate in the GI tract. We investigated the effect of silica NPs on NoV replication and host cell response during virus infection, using murine norovirus (MNV-1) infection of RAW 264.7 murine macrophages. Pretreatment with 10μg/ml silica significantly reduced the viability of macrophages, but no cumulative effects on viability of macrophages were observed with MNV-1 infection. No difference was observed between exposure to control or silica NPs on either the quantity of viral genome copies or the production of infectious virus in macrophages infected with MNV-1. Silica NPs reduced the ability of macrophages to upregulate genes encoding bone morphogenic proteins (BMPs), chemokine ligands and cytokines for which expression levels were otherwise found to be upregulated in response to MNV-1 infection. Furthermore, silica NPs reduced the levels of proinflammatory cytokines secreted by macrophages in response to MNV infection. Finally, silica NPs with MNV-1 infection produced a genotoxic insult to macrophages. Strikingly, this genotoxic insult was also found to occur as a synergistic effect of silica NPs and feline calicivirus infection in feline kidney epithelial cells. Taken together, our study suggests important safety considerations related to reducing exposure to silica NPs affecting the GI tract in individuals infected with NoVs and possibly other foodborne viruses.
authors.affiliation: United States Food and Drug Administration, National Center for Toxicological Research (NCTR), Division of Microbiology, Honolulu, Hawaii, 96816, USA.
authors.forename: Sudhakar S
authors.initials: SS
authors.lastname: Agnihothram
authors.affiliation: United States Food and Drug Administration, National Center for Toxicological Research (NCTR), Division of Microbiology, Honolulu, Hawaii, 96816, USA; Chaminade University of Honolulu, Honolulu, Hawaii, 96816, USA.
authors.forename: Sheryl Anne
authors.initials: SA
authors.lastname: Vermudez
authors.affiliation: United States Food and Drug Administration, National Center for Toxicological Research (NCTR), Division of Microbiology, Honolulu, Hawaii, 96816, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Mullis
authors.affiliation: United States Food and Drug Administration, National Center for Toxicological Research (NCTR), Division of Genetic and Molecular Toxicology, Honolulu, Hawaii, 96816, USA.
authors.forename: Todd A
authors.initials: TA
authors.lastname: Townsend
authors.affiliation: United States Food and Drug Administration, National Center for Toxicological Research (NCTR), Division of Genetic and Molecular Toxicology, Honolulu, Hawaii, 96816, USA.
authors.forename: Mugimane G
authors.initials: MG
authors.lastname: Manjanatha
authors.affiliation: United States Food and Drug Administration, National Center for Toxicological Research (NCTR), Division of Microbiology, Honolulu, Hawaii, 96816, USA.
authors.forename: Marli P
authors.initials: MP
authors.lastname: Azevedo
keywords: Feline Calicivirus; Genotoxicity; Murine Norovirus; Proinflammatory Response; Silica