Expression of Human Decay-Accelerating Factor on Intestinal Epithelium of Transgenic Mice Does Not Facilitate Infection by the Enteral Route

Pan, Jieyan; Zhang, Lili; Odenwald, Matthew A.; Shen, Le; Turner, Jerrold R.; Bergelson, Jeffrey M.

doi:10.1128/jvi.03468-14

Cited by 14 publications

(12 citation statements)

References 48 publications

(36 reference statements)

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“…These findings illuminate clear differences between the natural human host, and the murine model of infection. Expression of the human form of DAF on the intestinal epithelium in transgenic mice failed to facilitate infection by the enteral route (Pan, Zhang et al, 2015), suggesting that other obstacles such as the type I interferon response (Ohka, Igarashi et al, 2007) and interactions with the intestinal flora (Kuss, Etheredge et al, 2008) may limit CVB infection in the murine model.…”

Section: Introductionmentioning

confidence: 99%

Recent progress in understanding coxsackievirus replication, dissemination, and pathogenesis

et al. 2015

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Coxsackieviruses (CVs) are relatively common viruses associated with a number of serious human diseases, including myocarditis and meningo-encephalitis. These viruses are considered cytolytic yet can persist for extended periods of time within certain host tissues requiring evasion from the host immune response and a greatly reduced rate of replication. A member of Picornaviridae family, CVs have been historically considered non-enveloped viruses – although recent evidence suggest that CV and other picornaviruses hijack host membranes and acquire an envelope. Acquisition of an envelope might provide distinct benefits to CV virions, such as resistance to neutralizing antibodies and efficient nonlytic viral spread. CV exhibits a unique tropism for progenitor cells in the host which may help to explain the susceptibility of the young host to infection and the establishment of chronic disease in adults. CVs have also been shown to exploit autophagy to maximize viral replication and assist in unconventional release from target cells. In this article, we review recent progress in clarifying virus replication and dissemination within the host cell, identifying determinants of tropism, and defining strategies utilized by the virus to evade the host immune response. Also, we will highlight unanswered questions and provide future perspectives regarding the potential mechanisms of CV pathogenesis.

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Section: Introductionmentioning

confidence: 99%

Recent progress in understanding coxsackievirus replication, dissemination, and pathogenesis

et al. 2015

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“…Although murine models have been developed for the study of enterovirusinduced disease (1)(2)(3)(4), many of these models require intraperitoneal (i.p.) infection, thereby bypassing the GI tract, or require ablation of the host innate immune system (5,6). Coupled with species differences between humans and mice, there remains a need to develop human-based platforms to model enterovirus infections of the GI tract.…”

mentioning

confidence: 99%

Enteroviruses infect human enteroids and induce antiviral signaling in a cell lineage-specific manner

Drummond

Bolock

et al. 2017

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

131

173

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Enteroviruses are among the most common viral infectious agents of humans and are primarily transmitted by the fecal-oral route. However, the events associated with enterovirus infections of the human gastrointestinal tract remain largely unknown. Here, we used stem cell-derived enteroids from human small intestines to study enterovirus infections of the intestinal epithelium. We found that enteroids were susceptible to infection by diverse enteroviruses, including echovirus 11 (E11), coxsackievirus B (CVB), and enterovirus 71 (EV71), and that contrary to an immortalized intestinal cell line, enteroids induced antiviral and inflammatory signaling pathways in response to infection in a virus-specific manner. Furthermore, using the Notch inhibitor dibenzazepine (DBZ) to drive cellular differentiation into secretory cell lineages, we show that although goblet cells resist E11 infection, enteroendocrine cells are permissive, suggesting that enteroviruses infect specific cell populations in the human intestine. Taken together, our studies provide insights into enterovirus infections of the human intestine, which could lead to the identification of novel therapeutic targets and/or strategies to prevent or treat infections by these highly clinically relevant viruses.E nteroviruses are significant sources of human infections worldwide and are primarily transmitted by the fecal-oral route. Nonpoliovirus enteroviruses include coxsackievirus, echovirus, enterovirus 71 (EV71), and enterovirus D68 (EV-D68) and are small (∼30 nm) single-stranded RNA viruses belonging to the Picornaviridae family. In many cases, enterovirus infections remain asymptomatic, whereas in others, infection is associated with mild flu-like symptoms or much more severe outcomes such as type I diabetes, encephalomyelitis, encephalitis, myocarditis, dilated cardiomyopathy, pleurodynia, acute flaccid paralysis, or even death.The human gastrointestinal (GI) tract is a complex organ, with an epithelial surface that must provide a protective and immunological barrier in a complex and diverse microbial environment. The epithelium of the small intestine contains at least seven distinct cell subtypes that are responsible for the physiological functions of the intestine, which include nutrient absorption and defense against pathogens. The lack of models that recapitulate the complexity of the GI tract has hindered studies into many aspects of enterovirus infection in this specialized environment. Although murine models have been developed for the study of enterovirusinduced disease (1-4), many of these models require intraperitoneal (i.p.) infection, thereby bypassing the GI tract, or require ablation of the host innate immune system (5, 6). Coupled with species differences between humans and mice, there remains a need to develop human-based platforms to model enterovirus infections of the GI tract.The full repertoire of mature cells in the small intestine in vivo includes those of absorptive (enterocytes) and secretory (Paneth, goblet, and enteroendocrine) lin...

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“…DAF, a co-receptor of CAR, is expressed on CD4 + T cells and facilitates CVB3 internalization by increasing the binding efficiency of CVB3 on the DAF-CAR complex. Although Patel et al considered that the interaction between CVB3 and DAF alone was insufficient for CVB3 infection (Patel et al, 2009), Pan et al indicated that CVB3 infection of human intestinal epithelial cells without CAR expression was dependent on DAF (Pan et al, 2015). Furthermore, Martino et al showed that anti-DAF mAb blocked coxsackie virus infection of susceptible HeLa cells by reducing viral adhesion and internalization (Martino et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Coxsackievirus B3 Directly Induced Th17 Cell Differentiation by Inhibiting Nup98 Expression in Patients with Acute Viral Myocarditis

Long

Liao

Xie

et al. 2016

Front. Cell. Infect. Microbiol.

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Th17 cells play a key role in the progression of coxsackievirus B3 (CVB3)-induced acute viral myocarditis (AVMC). However, the direct effect of virus on Th17 cell differentiation is still unknown. Recently, nucleoporin (Nup) 98 has been proved to be associated with lymphocyte differentiation. Therefore, we investigated whether Nup98 mediated Th17 cell differentiation in AVMC. In our study, patients with AVMC and healthy controls were recruited. The results showed that CVB3 could enter into the CD4+ T cells in AVMC patients and healthy controls. After transfecting purified CD4+ T cells with CVB3 in vitro, the Th17 cell frequency, IL-17 secretion, and RORγT synthesis were increased while the Nup98 levels were decreased. Furthermore, down-regulating Nup98 expression by siRNA-Nup98 in CD4+ T cells resulted in the elevated Th17 cell frequency and IL-17 secretion, along with enhanced levels of RORγT, dissociative p300/CBP, and acetylated Stat3. Up-regulation of Nup98 expression by pcDNA3.1-Nup98 showed the opposite effects. Our results suggested that CVB3 directly induced CD4+ T cell differentiation into Th17 cells by inhibiting Nup98 expression, representing a therapeutic target in AVMC.

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Expression of Human Decay-Accelerating Factor on Intestinal Epithelium of Transgenic Mice Does Not Facilitate Infection by the Enteral Route

Cited by 14 publications

References 48 publications

Recent progress in understanding coxsackievirus replication, dissemination, and pathogenesis

Recent progress in understanding coxsackievirus replication, dissemination, and pathogenesis

Enteroviruses infect human enteroids and induce antiviral signaling in a cell lineage-specific manner

Coxsackievirus B3 Directly Induced Th17 Cell Differentiation by Inhibiting Nup98 Expression in Patients with Acute Viral Myocarditis

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