Cell-type specificity and functional redundancy of RIG-I-like receptors in innate immune sensing of Coxsackievirus B3 and encephalomyocarditis virus

Francisco, Esther; Suthar, Mehul S.; Gale, Michael; Rosenfeld, Amy; Racaniello, Vincent R.

doi:10.1016/j.virol.2018.12.003

Cited by 14 publications

(12 citation statements)

References 47 publications

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“…However, though the relative importance of MDA5 and RIG-I in HMPV-induced IFN expression is not fully elucidated, the cell-type-dependent fold induction of RIG-I relative to MDA5 mRNA expression in our study is in agreement with previous reports in A549 cells and MDDCs [7, 8]. Other pattern recognition receptors may additionally be involved in HMPV infection, e.g., TLR4 and TLR3 [40, 53], but we chose to focus on RIG-I-like receptors as these receptors have been shown to be critical for, and of similar importance for, innate immune sensing of RNA viruses in epithelial cells [51, 54], macrophages [55], and conventional DCs [51]. Also, we did not detect significant changes in TLR4 mRNA or protein levels (data not shown).…”

Section: Discussionsupporting

confidence: 60%

Cell-Type-Specific Transcription of Innate Immune Regulators in response to HMPV Infection

Loevenich

Malmo

Liberg

et al. 2019

Mediators of Inflammation

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Human metapneumovirus (HMPV) may cause severe respiratory disease. The early innate immune response to viruses like HMPV is characterized by induction of antiviral interferons (IFNs) and proinflammatory immune mediators that are essential in shaping adaptive immune responses. Although innate immune responses to HMPV have been comprehensively studied in mice and murine immune cells, there is less information on these responses in human cells, comparing different cell types infected with the same HMPV strain. The aim of this study was to characterize the HMPV-induced mRNA expression of critical innate immune mediators in human primary cells relevant for airway disease. In particular, we determined type I versus type III IFN expression in human epithelial cells and monocyte-derived macrophages (MDMs) and dendritic cells (MDDCs). In epithelial cells, HMPV induced only low levels of IFN-β mRNA, while a robust mRNA expression of IFN-λs was found in epithelial cells, MDMs, and MDDCs. In addition, we determined induction of the interferon regulatory factors (IRFs) IRF1, IRF3, and IRF7 and critical inflammatory cytokines (IL-6, IP-10, and IL-1β). Interestingly, IRF1 mRNA was predominantly induced in MDMs and MDDCs. Overall, our results suggest that for HMPV infection of MDDCs, MDMs, NECs, and A549 cells (the cell types examined), cell type is a strong determinator of the ability of HMPV to induce different innate immune mediators. HMPV induces the transcription of IFN-β and IRF1 to higher extents in MDMs and MDDCs than in A549s and NECs, whereas the induction of type III IFN-λ and IRF7 is considerable in MDMs, MDDCs, and A549 epithelial cells.

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Section: Discussionsupporting

confidence: 60%

Cell-Type-Specific Transcription of Innate Immune Regulators in response to HMPV Infection

Loevenich

Malmo

Liberg

et al. 2019

Mediators of Inflammation

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“…These PRRs sense non-self RNA from viral pathogens. In contrast to other PRRs like TLRS, RLRs are expressed in immune cells as well as in somatic cell types such as epithelium, thus can protect cell types most targeted by viral infection (Uhlen et al, 2015;Francisco et al, 2019). RLRs involved in IAV recognition include retinoic acid inducible gene I (RIG-I), melanoma differentiationassociated gene 5 (MDA5), and laboratory of genetics and physiology 2 (LGP2) (Figure 1).…”

Section: Rlr Receptors and Their Adaptorsmentioning

confidence: 99%

Pattern Recognition Receptor Signaling and Innate Responses to Influenza A Viruses in the Mallard Duck, Compared to Humans and Chickens

Campbell

Magor

2020

Front. Cell. Infect. Microbiol.

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Mallard ducks are a natural host and reservoir of avian Influenza A viruses. While most influenza strains can replicate in mallards, the virus typically does not cause substantial disease in this host. Mallards are often resistant to disease caused by highly pathogenic avian influenza viruses, while the same strains can cause severe infection in humans, chickens, and even other species of ducks, resulting in systemic spread of the virus and even death. The differences in influenza detection and antiviral effectors responsible for limiting damage in the mallards are largely unknown. Domestic mallards have an early and robust innate response to infection that seems to limit replication and clear highly pathogenic strains. The regulation and timing of the response to influenza also seems to circumvent damage done by a prolonged or dysregulated immune response. Rapid initiation of innate immune responses depends on viral recognition by pattern recognition receptors (PRRs) expressed in tissues where the virus replicates. RIG-like receptors (RLRs), Toll-like receptors (TLRs), and Nod-like receptors (NLRs) are all important influenza sensors in mammals during infection. Ducks utilize many of the same PRRs to detect influenza, namely RIG-I, TLR7, and TLR3 and their downstream adaptors. Ducks also express many of the same signal transduction proteins including TBK1, TRIF, and TRAF3. Some antiviral effectors expressed downstream of these signaling pathways inhibit influenza replication in ducks. In this review, we summarize the recent advances in our understanding of influenza recognition and response through duck PRRs and their adaptors. We compare basal tissue expression and regulation of these signaling components in birds, to better understand what contributes to influenza resistance in the duck.

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“…For EV-A71, tissue culture studies revealed that the viral RNA-dependent RNA-polymerase (3D pol ) and viral 3C pro interacts with MDA5 and antagonizes the antiviral immune response (Kuo et al, 2013(Kuo et al, , 2019Rui et al, 2017) in addition to inhibiting RIG-I ubiquitination by 3C pro (Chen et al, 2016). These host-virus interactions were largely depended on the type of virus, cell type and genetic background of the host (Francisco et al, 2019), further underlying the adaptive capabilities of enteroviruses and the need to study these viruses within CNS-relevant cells to better understand the development of neurological disease.…”

Section: Innate Immune Response and Enterovirus Countermeasuresmentioning

confidence: 99%

Molecular Pathogenicity of Enteroviruses Causing Neurological Disease

Majer¹,

McGreevy

Booth

2020

Front. Microbiol.

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Enteroviruses are single-stranded positive-sense RNA viruses that primarily cause self-limiting gastrointestinal or respiratory illness. In some cases, these viruses can invade the central nervous system, causing life-threatening neurological diseases including encephalitis, meningitis and acute flaccid paralysis (AFP). As we near the global eradication of poliovirus, formerly the major cause of AFP, the number of AFP cases have not diminished implying a non-poliovirus etiology. As the number of enteroviruses linked with neurological disease is expanding, of which many had previously little clinical significance, these viruses are becoming increasingly important to public health. Our current understanding of these non-polio enteroviruses is limited, especially with regards to their neurovirulence. Elucidating the molecular pathogenesis of these viruses is paramount for the development of effective therapeutic strategies. This review summarizes the clinical diseases associated with neurotropic enteroviruses and discusses recent advances in the understanding of viral invasion of the central nervous system, cell tropism and molecular pathogenesis as it correlates with host responses.

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Cell-type specificity and functional redundancy of RIG-I-like receptors in innate immune sensing of Coxsackievirus B3 and encephalomyocarditis virus

Cited by 14 publications

References 47 publications

Cell-Type-Specific Transcription of Innate Immune Regulators in response to HMPV Infection

Cell-Type-Specific Transcription of Innate Immune Regulators in response to HMPV Infection

Pattern Recognition Receptor Signaling and Innate Responses to Influenza A Viruses in the Mallard Duck, Compared to Humans and Chickens

Molecular Pathogenicity of Enteroviruses Causing Neurological Disease

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