Diversity of Interferon Antagonist Activities Mediated by NSP1 Proteins of Different Rotavirus Strains

Arnold, Michelle M.; Patton, John T.

doi:10.1128/jvi.01801-10

Cited by 83 publications

(150 citation statements)

References 38 publications

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“…Rotavirus antagonizes IFN production pretranscriptionally in a variety of cell lines (HT29, Caco-2, and 293T) through degradation of factors involved in IFN transcription (35,(49)(50)(51). We observed robust type III IFN transcription with HRV and poly (I:C) treatment (∼100-1,000-fold increases; Fig.…”

Section: Different Strains Of Rotavirus and A Dsrna Analog Preferentimentioning

confidence: 62%

“…Rotavirus evades the host innate response primarily through its nonstructural proteins NSP1 and NSP3, and the structural protein VP3 has recently been shown to antagonize the cellular RNaseL antiviral response as well (33,76). In several in vitro models, rotavirus NSP1 inhibits the host IFN response by preventing IFN from being transcribed (35,51). Recent studies have shown that NSP1 acts as an adaptor that links the host Cullin-E3 ligase complex with β-transducin repeat-containing protein (β-TrCP), which is a necessary component for NF-κB-mediated induction of IFN transcripts (77,78).…”

Section: Discussionmentioning

confidence: 99%

“…Although a wealth of knowledge has been gained from mouse studies with nonhuman enteric viruses, these models do not account for evolutionary differences in host and pathogen. Subtle but possibly important differences exist between human and mouse type I and III IFN systems and between human and mouse rotaviruses (18,(35)(36)(37)(38), necessitating functional studies of interactions between human host cells and human enteric pathogens.…”

Section: Significancementioning

confidence: 99%

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A paradox of transcriptional and functional innate interferon responses of human intestinal enteroids to enteric virus infection

Saxena

Simon

Zeng

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

116

150

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The intestinal epithelium can limit enteric pathogens by producing antiviral cytokines, such as IFNs. Type I IFN (IFN-α/β) and type III IFN (IFN-λ) function at the epithelial level, and their respective efficacies depend on the specific pathogen and site of infection. However, the roles of type I and type III IFN in restricting human enteric viruses are poorly characterized as a result of the difficulties in cultivating these viruses in vitro and directly obtaining control and infected small intestinal human tissue. We infected nontransformed human intestinal enteroid cultures from multiple individuals with human rotavirus (HRV) and assessed the host epithelial response by using RNAsequencing and functional assays. The dominant transcriptional pathway induced by HRV infection is a type III IFN-regulated response. Early after HRV infection, low levels of type III IFN protein activate IFN-stimulated genes. However, this endogenous response does not restrict HRV replication because replication-competent HRV antagonizes the type III IFN response at pre-and posttranscriptional levels. In contrast, exogenous IFN treatment restricts HRV replication, with type I IFN being more potent than type III IFN, suggesting that extraepithelial sources of type I IFN may be the critical IFN for limiting enteric virus replication in the human intestine.enteric virus | interferon | human enteroids | human rotavirus T he human small intestinal epithelium is the primary site of infection and replication for many gastrointestinal pathogens. However, fundamental knowledge about intestinal epithelial cellpathogen interactions in humans is limited as a result of the impracticality of studying these cells in vivo. Modeling these interactions in vitro is difficult because many human enteric pathogens fail to replicate or replicate poorly in cancer cell lines derived primarily from the human colon (1-4). Human intestinal enteroids (HIEs) represent a new in vitro model of the human small intestinal epithelium; this model was developed following advances in stem cell biology, and it recapitulates many of the biological and physiological properties of the human small intestine in vivo (5, 6). Unlike other in vitro models, HIEs are easily established from nontransformed small intestinal tissue, can be maintained on a long-term basis, and contain a stem cell niche and the diversity of intestinal epithelial cell types (enterocytes, goblet, enteroendocrine, and Paneth cells) present in vivo (6, 7). HIEs allow for comparisons of intestinal host responses across genetically diverse individuals (8) and reproduce many of the in vivo pathophysiological properties of infection by a human enteric viral pathogen, human rotavirus (HRV) (9).HRVs are the major etiology of severe diarrhea in children under the age of 5 y worldwide, resulting in an estimated 215,000 deaths annually (10). HRVs replicate to high titers in humans but replicate poorly or not at all in small animal models (11,12). This host restriction of HRV in animal models is based on properties o...

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Section: Different Strains Of Rotavirus and A Dsrna Analog Preferentimentioning

confidence: 62%

Section: Discussionmentioning

confidence: 99%

Section: Significancementioning

confidence: 99%

See 1 more Smart Citation

A paradox of transcriptional and functional innate interferon responses of human intestinal enteroids to enteric virus infection

Saxena

Simon

Zeng

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

116

150

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“…As opposed to the IFN-dependent phenotypes of heterologous RV replication in vivo, most RV strains studied so far (e.g., simian RRV) are capable of inhibiting the induction of IFN in vitro (15,21,22). However, certain exceptions have been reported, including the bovine UK rotavirus strain in murine fibroblasts (15,23) and several isolates of RV that encode truncated NSP1 proteins and form small plaques in interferon-competent cells in culture (24,25).…”

mentioning

confidence: 95%

“…UK NSP1 degrades the endogenous IRF3 expressed in simian COS7 cells, and simian IRF3 can also be efficiently degraded by UK NSP1 when transiently expressed in mouse embryonic fibroblasts (MEFs) (23). Other studies have shown that NSP1 degrades additional IRFs, including IRF5 and IRF7 (22,25), indicating that apart from IRF3-dependent IFN induction, other IRF-specific responses may also be regulated by rotavirus during infection. Previous studies have also described NSP1-mediated inhibition of IFN induction by inhibition of RIG-I (31) and inhibition of poly(I·C)-directed IRF3-dependent transcription in the absence of any IRF3 degradation (23).…”

mentioning

confidence: 99%

Rotavirus NSP1 Protein Inhibits Interferon-Mediated STAT1 Activation

Rott

Phan

et al. 2014

J Virol

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Rotavirus: Genetics, pathogenesis and vaccine advances

Sadiq

Bostan

Yinda

et al. 2018

Reviews in Medical Virology

103

110

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Since its discovery 40 years ago, rotavirus (RV) is considered to be a major cause of infant and childhood morbidity and mortality particularly in developing countries. Nearly every child in the world under 5 years of age is at the risk of RV infection. It is estimated that 90% of RV-associated mortalities occur in developing countries of Africa and Asia. Two live oral vaccines, RotaTeq (RV5, Merck) and Rotarix (RV1, GlaxoSmithKline) have been successfully deployed to scale down the disease burden in Europe and America, but they are less effective in Africa and Asia. In April 2009, the World Health Organization recommended the inclusion of RV vaccination in national immunization programs of all countries with great emphasis in developing countries. To date, 86 countries have included RV vaccines into their national immunization programs including 41 Global Alliance for Vaccines and Immunization eligible countries. The predominant RV genotypes circulating all over the world are G1P[8], G2P[4], G3P[8], G4P[8], and G9P[8], while G12[P6] and G12[P8] are emerging genotypes. On account of the segmented genome, RV shows an enormous genetic diversity that leads to the evolution of new genotypes that can influence the efficacy of current vaccines. The current need is for a global RV surveillance program to monitor the prevalence and antigenic variability of new genotypes to formulate future vaccine development planning. In this review, we will summarize the previous and recent insights into RV structure, classification, and epidemiology and current status of RV vaccination around the globe and will also cover the status of RV research and vaccine policy in Pakistan.

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Diversity of Interferon Antagonist Activities Mediated by NSP1 Proteins of Different Rotavirus Strains

Cited by 83 publications

References 38 publications

A paradox of transcriptional and functional innate interferon responses of human intestinal enteroids to enteric virus infection

A paradox of transcriptional and functional innate interferon responses of human intestinal enteroids to enteric virus infection

Rotavirus NSP1 Protein Inhibits Interferon-Mediated STAT1 Activation

Rotavirus: Genetics, pathogenesis and vaccine advances

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