The Role of Innate Immunity in Regulating Rotavirus Replication, Pathogenesis, and Host Range Restriction and the Implications for Live Rotaviral Vaccine Development

A, Sen; Ding, Siyuan; Greenberg, Harry B.

doi:10.1016/b978-0-12-811924-2.00041-9

Cited by 4 publications

(4 citation statements)

References 80 publications

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“…It is noteworthy that rotaviral antigens were observed within circulating immune cells in the blood vessels of gastric tumor tissue, as well as a change in the tissue lymphocyte infiltrate. This finding is relevant since previous studies [41][42][43][44] have shown that RV can activate macrophages, which are involved in the secretion of proinflammatory cytokines, and dendritic cells, favoring the presentation of antigens and the induction of effector T lymphocytes and B lymphocytes. These mechanisms could be fundamental to conducting future studies using the ex vivo infection model developed in the present work to demonstrate the ability of the RV to reactivate immunosurveillance in the tumor.…”

Section: Discussionmentioning

confidence: 70%

Cultivo de explantes de adenocarcinoma gástrico humano: Modelo para la evaluación de la actividad oncolítica del rotavirus Wt1-5

Sossa-Rojas,

Franco-Maz,

Zapata-Acevedo

et al. 2023

Rev. Fac. Med.

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Introducción. A nivel mundial, el cáncer gástrico es el quinto cáncer más comúnmente diagnosticado y la cuarta mayor causa de mortalidad por cáncer. Los virus oncolíticos son un agente terapéutico potencial para el cáncer. Objetivo. Evaluar la capacidad de penetración, la selectividad y la eficiencia oncolítica del rotavirus Wt1-5 mediante un modelo de infección ex vivo en muestras tumorales obtenidas de pacientes con diagnóstico de adenocarcinoma gástrico. Materiales y métodos. Estudio experimental de laboratorio realizado en explantes de adenocarcinoma gástricos de subtipo-difuso e intestinal recolectados en el Hospital Universitario de la Samaritana (Bogotá D.C., Colombia). Estos explantes se infectaron con el rotavirus Wt1-5 y, mediante pruebas inmunohistoquímicas, se evaluó su capacidad de penetración y difusión a través del microambiente tumoral, así como su potencial como virus oncolítico. Los datos se describen usando medias y desviaciones estándar. Además, se realizó un análisis bivariado mediante la prueba de U de Mann-Whitney para determinar las diferencias entre los datos de los ensayos evaluados y el control empleado en cada uno. Se consideró un nivel de significancia estadística de p <0.05. Resultados. A las 12 horas post infección (h.p.i) se observó que el rotavirus Wt1- se había diseminado en todas las capas del tumor, lo cual favoreció la infección de las células tumorales y generó necrosis del tejido tumoral a partir de las 48 h.p.i. Por otro lado, los tejidos no-tumorales adyacentes no mostraron evidencia de infección con este rotavirus, ni lisis tisular (p<0.05). Conclusiones. El cultivo de explantes es un modelo útil para estudiar y predecir el comportamiento infeccioso ex vivo. El rotavirus Wt1-5 infecta de manera selectiva y eficiente las células tumorales en explantes de adenocarcinoma gástrico, tanto del subtipo difuso como del subtipo intestinal.

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Section: Discussionmentioning

confidence: 70%

Cultivo de explantes de adenocarcinoma gástrico humano: Modelo para la evaluación de la actividad oncolítica del rotavirus Wt1-5

Sossa-Rojas,

Franco-Maz,

Zapata-Acevedo

et al. 2023

Rev. Fac. Med.

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“…Ротавирусная инфекция сохраняет лидирующие позиции среди острых кишечных инфекций (ОКИ) у детей в возрасте до 5 лет не только в России, но и во всем мире, несмотря на внедрение в ряде стран вакцинации против этого заболевания [2,8]. По данным Роспотребнадзора показатель заболеваемости ротавирусной инфекцией в нашей стране в 2021 г. составил 49,77 на 100 тыс.…”

Section: Introductionunclassified

“…Заражение плазмоцитоидных дендритных клеток ротавирусом приводит к эндосомозависимой (и, возможно, опосредо-ванной TLR7) секреции IFN I типа, которая запускается вирусной двухцепочечной РНК. На центральную роль TLR-зависимой защиты от ротавируса также указывает тот факт, что отсутствие MyD88 (важного адаптерного белка, участвующего в передаче сигналов от различных TLR) приводит к повышению вирулентности этого возбудителя, тяжести диареи и нарушению гуморального иммунитета [8].…”

Section: Introductionunclassified

TLR3 and TLR7 prognostic role in early pediatric rotavirus infection

Gorbunov,

Mazankova,

Os'kin

2023

Russian Journal of Infection and Immunity

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Introduction. Rotavirus infection is an urgent problem for pediatric infectology. The disease does not always proceed smoothly, it is assumed that TLR3 and TLR7 play an important role in its prognosis. The initial number of cells expressing such receptors in early children can probably be considered a predictor of unfavorable course and outcomes of rotavirus infection. Materials and methods. Infants with rotavirus infection were divided into groups depending on the initial count of TLR3- and TLR7-expressing immunocompetent cells. All patients were examined using general clinical methods. Rotavirus infection was diagnosed by molecular genetic (RNA detected by PCR) and immunochromatographic (determination of antigen) method. Parameters of cellular immunity were assessed by flow cytometry. Statistical data processing was carried out using the Statistica 8.0 program for independent samples using the nonparametric MannWhitney criterion and the Pearson criterion c2. Results. It was found that in patients with an initially small vs. high count of TLR3-expressing cells, the symptoms of exicosis were observed significantly longer, which determined a significantly longer infusion rehydration therapy. In patients with an initially small count of TLR7-expressing cells, no significant differences were observed during disease course. However, only this group similar to infants with a small count of TLR3-expressing cells were treated with antibiotics due to concomitant bacterial infections. Only convalescents with small count of simultaneously TLR3- and TLR7-expressing cells had repeated episodes of ARI and allergic diseases in catamnesis, whereas infants with extremely low count of TLR3-expressing cells developed additionally an unfavorable outcome such as reactive pancreatopathy. Conclusion. The initially low count of TLR3- and TLR7-expressing immunocompetent cells leads to a more severe course of rotavirus infection in infants requiring adjusted therapy by introducing antibacterial drugs and in some cases also contributes to arising adverse outcomes and consequences in 612 month catamnesis.

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“…Both natural infection and vaccination generally elicit strong adaptive immunity, which is essential for clearance of primary infection as well as protection from reinfection. While the innate immune signaling pathways leading to the control of the initial viral replication have been dissected in detail ( 2 ), the requirements for the induction of adaptive immunity to RV remain less well understood.…”

Section: Introductionmentioning

confidence: 99%

Rotavirus-Induced Expansion of Antigen-Specific CD8 T Cells Does Not Require Signaling via TLR3, MyD88 or the Type I Interferon Receptor

et al. 2022

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Rotavirus (RV) infection induces strong adaptive immunity. While protection from reinfection requires humoral immunity, initial clearance of infection depends on cytotoxic CD8 T cells. Type I classical dendritic cells (cDC1) excel at CD8 T cell induction through cross-presentation and are essential for optimal cytotoxicity towards RV. Upon sensing of infection-induced innate immune signals through pattern recognition receptors (PRRs), cumulating in autocrine type I interferon (IFN) signaling, cDC1 mature and migrate to the draining lymph nodes (LNs), where they prime adaptive immune cells. To analyze which PRR pathways lead to robust cytotoxicity in the context of RV infection, we measured RV-specific CD8 T cell priming in mice deficient for Toll-like receptor 3 (TLR3), recognizing double-stranded RNA, or for MyD88, the adapter for all other TLRs and IL-1 family cytokines. Individual TLR3- and MyD88-mediated signaling was not required for the priming of CD8 T cell responses to RV and neither deficiency impacted on RV clearance. Surprisingly, the accumulation of RV-specific CD8 T cells was also not altered in the absence of type I IFN signaling, while their ability to produce IFNγ and granzyme were blunted. Together, this suggests a substantial level of redundancy in the sensing of RV infection and the translation of signals into protective CD8 T cell immunity.

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The Role of Innate Immunity in Regulating Rotavirus Replication, Pathogenesis, and Host Range Restriction and the Implications for Live Rotaviral Vaccine Development

Cited by 4 publications

References 80 publications

Cultivo de explantes de adenocarcinoma gástrico humano: Modelo para la evaluación de la actividad oncolítica del rotavirus Wt1-5

Cultivo de explantes de adenocarcinoma gástrico humano: Modelo para la evaluación de la actividad oncolítica del rotavirus Wt1-5

TLR3 and TLR7 prognostic role in early pediatric rotavirus infection

Rotavirus-Induced Expansion of Antigen-Specific CD8 T Cells Does Not Require Signaling via TLR3, MyD88 or the Type I Interferon Receptor

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