Critical role of RIG-I and MDA5 in early and late stages of Tulane virus infection

Abstract

Human noroviruses are a major cause of acute gastroenteritis worldwide, but the lack of a robust cell culture system or small animal model have hampered a better understanding of innate immunity against these viruses. Tulane virus (TV) is the prototype virus of a tentative new genus, Recovirus, in the family Caliciviridae. Its epidemiology and biological properties most closely resemble human norovirus. The host innate immune response to RNA virus infection primarily involves pathogen-sensing toll-like receptors (TLRs) TLR3 and TLR7 and retinoic acid-inducible gene I-like receptor RIG-I and melanoma differentiation associated gene 5 (MDA5). In this study, by using siRNA knockdown, we report that TV infection in LLC-MK2 cells results in an early [3 h post infection (h p.i.), P<0.05] RIG-I-dependent and type I interferon-mediated antiviral response, whereas an MDA5-mediated antiviral effect was observed at later (12 h p.i.; P<0.05) stages of TV replication. Induction of RIG-I and MDA5 was critical for inhibition of TV replication. Furthermore, pre-activation of the RIG-I/MDA5 pathway prevented TV replication (>900-fold decrease; P<0.05), suggesting that RIG-I and MDA5 ligands could be used to develop novel preventive and therapeutic measures against norovirus.

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

“…After 3–5 days, cells showing cytopathic effect (CPE) were enumerated and the Tulane virus titer was calculated as log 10 ( N x / N 0 ), where N 0 is the infectious virus titer for untreated samples and N x is the infectious virus titer for aged-GTE-treated samples. To determine effect of aged-GTE on the viral genome, Tulane virus RNA was extracted as described above and detected by RT-qPCR ( Chhabra et al, 2017 ). Genome copies were calculated by using a standard curve of 10-fold serial dilutions of a purified 4 kb PCR product amplified from the 3'-end of the virus genome.…”

Interferon responses to norovirus infections: current and future perspectives

“…While the presence of VPg was always thought to protect the viral genome from RIG-I sensing [46,59], there is currently insufficient experimental evidence to rule it out as a sensor of noroviruses. Moreover, recent studies on picornaviruses and on the Tulane virus show that RIG-I can still detect viruses that have VPg-linked RNA genomes [60][61][62][63]. Other PRRs can also potentially participate in the recognition of noroviruses, including the DNA sensor cGAS for example, which was recently shown to indirectly recognise infection with dengue viruses by sensing leaked mitochondrial DNA [43,45].…”

Dual and mutual interaction between microbiota and viral infections: a possible treat for COVID-19

“…secreted component, protects mice from MNV-1 infection via regulating MNoV infection by increasing interferon-b (IFN-b) signaling pathways [151]. Although most of retinoic acid dependent studies investigated MNV, there are some studies revealing that retinoic acid treatment reduces the risk of HNoV infection [152]. The Lactobacillus bacteria suppress murine norovirus (MNV) replication via expression of interferons, like IFNβ and IFNγ and lower infection duration.…”