Rotavirus acceleration of type 1 diabetes in non-obese diabetic mice depends on type I interferon signalling

Pane, Jessica A.; Fleming, Fiona E.; Graham, Kerr; Thomas, Helen E.; Kay, Thomas W. H.; Coulson, Barbara S.

doi:10.1038/srep29697

Cited by 24 publications

(18 citation statements)

References 34 publications

(72 reference statements)

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“…In a previous study, we found an HBsAg-binding protein that could promote the immune process both in vitro and in vivo. Its adjuvanticity in connection with several antigens (HBsAg, rabies [16], and rotavirus [17]) has been evaluated in mice and the results indicate that it has the potential to be a new adjuvant for use in human vaccines.…”

Section: Discussionmentioning

confidence: 99%

A Pre-Clinical Safety Evaluation of SBP (HBsAg-Binding Protein) Adjuvant for Hepatitis B Vaccine

Wang

Liu

et al. 2017

PLoS ONE

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Although adjuvants are a common component of many vaccines, there are few adjuvants licensed for use in humans due to concerns about their toxic effects. There is a need to develop new and safe adjuvants, because some existing vaccines have low immunogenicity among certain patient groups. In this study, SBP, a hepatitis B surface antigen binding protein that was discovered through screening a human liver cDNA expression library, was introduced into hepatitis B vaccine. A good laboratory practice, non-clinical safety evaluation was performed to identify the side effects of both SBP and SBP-adjuvanted hepatitis B vaccine. The results indicate that SBP could enhance the HBsAg-specific immune response, thus increasing the protection provided by the hepatitis B vaccine. The safety data obtained here warrant further investigation of SBP as a vaccine adjuvant.

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Section: Discussionmentioning

confidence: 99%

A Pre-Clinical Safety Evaluation of SBP (HBsAg-Binding Protein) Adjuvant for Hepatitis B Vaccine

Wang

Liu

et al. 2017

PLoS ONE

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“…In a mouse model of diabetes, rotavirus infection activated plasmacytoid dendritic cells, leading to the secretion of type I interferon, which induces lymphocyte activation, including activation of islet autoreactive T cells 202,203 . However, contradictory findings have also been reported 204,205 .…”

Section: Figurementioning

confidence: 99%

Rotavirus infection

Crawford

Ramani

Tate

et al. 2017

Nat Rev Dis Primers

524

558

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Rotavirus infections are a leading cause of severe, dehydrating gastroenteritis in children <5 years of age. Despite the global introduction of vaccinations for rotavirus over a decade ago, rotavirus infections still result in >200,000 deaths annually, mostly in low-income countries. Rotavirus primarily infects enterocytes and induces diarrhoea through the destruction of absorptive enterocytes (leading to malabsorption), intestinal secretion stimulated by rotavirus non-structural protein 4 and activation of the enteric nervous system. In addition, rotavirus infections can lead to antigenaemia (which is associated with more severe manifestations of acute gastroenteritis) and viraemia, and rotavirus can replicate in systemic sites, although this is limited. Reinfections with rotavirus are common throughout life, although the disease severity is reduced with repeat infections. The immune correlates of protection against rotavirus reinfection and recovery from infection are poorly understood, although rotavirus-specific immunoglobulin A has a role in both aspects. The management of rotavirus infection focuses on the prevention and treatment of dehydration, although the use of antiviral and anti-emetic drugs can be indicated in some cases.

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“…Rotavirus infection is associated with progression to type 1 diabetes in children, and accelerates type 1 diabetes development in diabetes-prone NOD mice 28 . RRV rotavirus infection of NOD mice leads to MHCI upregulation on plasmacytoid dendritic cells and B cells in gut- and pancreas-draining lymph nodes 29 , 30 . However, <2% of these cells show evidence of RRV infection, indicating that they are predominantly bystander cells 31 .…”

Section: Discussionmentioning

confidence: 99%

MHC class I expression in intestinal cells is reduced by rotavirus infection and increased in bystander cells lacking rotavirus antigen

Holloway

Fleming

Coulson

2018

Sci Rep

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Detection of viral infection by host cells leads to secretion of type I interferon, which induces antiviral gene expression. The class I major histocompatibility complex (MHCI) is required for viral antigen presentation and subsequent infected cell killing by cytotoxic T lymphocytes. STAT1 activation by interferon can induce NLRC5 expression, promoting MHCI expression. Rotavirus, an important pathogen, blocks interferon signalling through inhibition of STAT1 nuclear translocation. We assessed MHCI expression in HT-29 intestinal epithelial cells following rotavirus infection. MHCI levels were upregulated in a partially type I interferon-dependent manner in bystander cells lacking rotavirus antigen, but not in infected cells. MHCI and NLRC5 mRNA expression also was elevated in bystander, but not infected, cells, suggesting a transcriptional block in infected cells. STAT1 was activated in bystander and infected cells, but showed nuclear localisation in bystander cells only. Overall, the lack of MHCI upregulation in rotavirus-infected cells may be at least partially due to rotavirus blockade of interferon-induced STAT1 nuclear translocation. The reduced MHCI protein levels in infected cells support the existence of an additional, non-transcriptional mechanism that reduces MHCI expression. It is possible that rotavirus also may suppress MHCI expression in vivo, which might limit T cell-mediated killing of rotavirus-infected enterocytes.

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Rotavirus acceleration of type 1 diabetes in non-obese diabetic mice depends on type I interferon signalling

Cited by 24 publications

References 34 publications

A Pre-Clinical Safety Evaluation of SBP (HBsAg-Binding Protein) Adjuvant for Hepatitis B Vaccine

A Pre-Clinical Safety Evaluation of SBP (HBsAg-Binding Protein) Adjuvant for Hepatitis B Vaccine

Rotavirus infection

MHC class I expression in intestinal cells is reduced by rotavirus infection and increased in bystander cells lacking rotavirus antigen

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