Human Intestinal Enteroids to Evaluate Human Norovirus GII.4 Inactivation by Aged-Green Tea

Abstract

Human noroviruses are the leading cause of epidemic and sporadic acute gastroenteritis worldwide and the most common cause of foodborne illness in the United States. Several natural compounds, such as aged-green tea extract (aged-GTE), have been suggested as ingestible antiviral agents against human norovirus based on data using murine norovirus and feline calicivirus as surrogates. However, in vitro data showing their effectiveness against infectious human norovirus are lacking. We tested the activity of aged-GTE to inhibit human norovirus in a human intestinal enteroids (HIEs) model and Tulane virus in LLC-monkey kidney (LLC-MK2) cell culture. HIE monolayers pretreated with aged-GTE at different temperatures showed complete inhibition of human norovirus GII.4 replication at concentrations as low as 1.0 mg/ml for 37°C, 1.75 mg/ml for 21°C, and 2.5 mg/ml for 7°C. In contrast, a moderate decrease in Tulane virus infectivity of 0.85, 0.75, and 0.65 log TCID 50 /ml was observed for 2.5 mg/ml aged-GTE at 37, 21, and 7°C, respectively. Our findings demonstrate that GTE could be an effective natural compound against human norovirus GII.4, while only minimally effective against Tulane virus.

Recovery of Infectious Human Norovirus GII.4 Sydney From Fomites via Replication in Human Intestinal Enteroids

“…Another potential option for quantifying recovered infectious HuNoV is the fold increase in GE between 1 and 72 hpi in HIEs. Consistent with previous work, we found that fold increases ranged from 10–10,000 and varied from 2–3 logs within tests that used equivalent surface inoculum ( Costantini et al., 2018 ; Chan et al., 2019 ; Randazzo et al., 2020 ). We are not the first to report high variability among measured fold increase in HIEs and this inconsistency remains a key challenge for application of the HIE system to monitoring infectious HuNoV ( Costantini et al., 2018 ; Estes et al., 2019 ; Koromyslova et al., 2019 ).…”

Organoids to Dissect Gastrointestinal Virus–Host Interactions: What Have We Learned?

“…HIOs may also provide a platform for evaluating antivirals aimed at chronically infected immunocompromised patients [87]. FDA-approved drugs, natural compounds, and other drugs that block new pathways important for human norovirus or human rotavirus replication are beginning to be reported [81,88,89].…”

Antiviral Potential of Plants against Noroviruses

“…The antiviral activity of plant metabolites is the subject of many scientific studies [ 23 , 41 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 ,…”

“…Randazzo et al [ 100 ] observed a complete inhibition of human norovirus GII.4 replication by aged-GTE at concentrations of 1 mg/mL at 37 °C, 1.75 mg/mL for 21 °C, and 2.5 mg/mL at 7 °C.…”