Enhanced expression of human endogenous retroviruses in new-onset type 1 diabetes: Potential pathogenetic and therapeutic implications

Tovo, Pier-Angelo; Rabbone, Ivana; Tinti, Davide; Galliano, Ilaria; Trada, M.; Daprà, Valentina; Cerutti, Fránco; Bergallo, Massimiliano

doi:10.1080/08916934.2020.1777281

Cited by 23 publications

(37 citation statements)

References 48 publications

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“…In patients with T1D, the activation of HERV-W ENV has been demonstrated: the ENV mRNA level was higher than that in the PBMCs of control subjects, and the ENV protein was detected in the serum and exocrine pancreas of patients with T1D [3]. Furthermore, the activation of pol genes of HERV-W in PBMCs of patients with new-onset T1D was recently reported [43]. The HERV-W ENV genomic copy encoding the pathogenic HERV-W ENV protein involved in T1D remains to be identified.…”

Section: Discussionmentioning

confidence: 93%

Coxsackievirus-B4 Infection Can Induce the Expression of Human Endogenous Retrovirus W in Primary Cells

Dechaumes¹,

Bertin²,

Sané³

et al. 2020

Microorganisms

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Human Endogenous Retrovirus W Envelope (HERV-W ENV) mRNA or protein can be found in peripheral blood mononuclear cells (PBMCs) and exocrine pancreas of patients with type 1 diabetes (T1D). Further, previous observations have shown an association between enteroviral infection and development of T1D; specifically, coxsackievirus-B (CV-B) has been detected in the blood and pancreas of patients with T1D. Notably, viruses can activate HERV-W expression. Hence, we evaluated the effect of CV-B4 infection on HERV-W ENV mRNA expression. Primary human pancreatic ductal cells were obtained from five brain-dead donors. In the pancreatic cells of three donors, the HERV-W ENV mRNA level measured using RT-qPCR was upregulated upon CV-B4 infection. The HERV-W ENV protein was detected in the infected cells using the immunoblot assay. In human PBMCs inoculated with CV-B4 or when CV-B4 was incubated with an enhancing serum, the HERV-W ENV mRNA level was higher than the background RNA level. In monocyte-derived macrophages obtained from 5 of 13 donors, the HERV-W ENV mRNA level was higher in cultures inoculated with CV-B4 than in the control. Therefore, CV-B4 can upregulate or induce the transcription of a certain HERV-W ENV copy (or copies) in primary cell cultures, such as monocytes, macrophages, and pancreatic cells.

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Section: Discussionmentioning

confidence: 93%

Coxsackievirus-B4 Infection Can Induce the Expression of Human Endogenous Retrovirus W in Primary Cells

Dechaumes¹,

Bertin²,

Sané³

et al. 2020

Microorganisms

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“…It should be stated upfront that despite the many genetic, experimental, and supportive correlative findings, it is still possible that none of the myriad of HERV and L1 sequences that constitute at least 25% of our genome (close to 40% if one includes Alu elements and other SINEs) have any role at all in autoimmunity because they have been sufficiently "domesticated" and have lost their immunogenicity and potential to raise an anti-viral response or to skew biological processes in any meaningful way. That said, there are many plausible aspects to the general hypothesis that HERVs and/or L1 can promote or even trigger autoimmunity (17,161,162). We believe that the vast majority of retroelements are harmless, some even beneficial (17), but that a select few are dangerous and participate in the pathogenesis of common autoimmune diseases like SLE or RA by mechanisms that are discussed below.…”

Section: Molecular Mechanisms By Which Endogenous Retroviruses and Rementioning

confidence: 98%

How Retroviruses and Retrotransposons in Our Genome May Contribute to Autoimmunity in Rheumatological Conditions

Mustelin

Ukadike

2020

Front. Immunol.

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“…Transcription levels of pol genes of HERV-H, -K, and -W, and of TRIM28 by real-time PCR assay Relative quantification of mRNA expression of HERV-H-pol, HERV-K-pol, and HERV-W-pol was achieved by means of PCR real-time TaqMan amplification and to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) using the ABI PRISM 7500 real-time system (Life Technologies, TX, USA). GAPDH was chosen as reference gene being one of the most stable among reference genes and already used in our previous studies [13][14][15]. A total of 40 ng of cDNA was amplified using HERV-H, -K, -W, and TRIM28 gene mRNA expression kit PP-BioMole-054, -055, -056, and 044 respectively (BioMole srl, Turin, Italy) in a 20-μl total volume reaction.…”

Section: Total Rna Extractionmentioning

confidence: 99%

Overexpression of endogenous retroviruses in children with celiac disease

et al. 2021

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Human endogenous retroviruses (HERVs) represent 8% of our genome. Although no longer infectious, they can regulate transcription of adjacent cellular genes, produce retroviral RNAs, and encode viral proteins that can modulate both innate and adaptive immune responses. Based on this, HERVs have been studied and proposed as contributing factors in various autoimmune disorders. Celiac disease (CD) is considered an autoimmune disease, but HERV expression has not been studied in celiac patients. The aim of this study is to assess the transcription levels of pol genes of HERV-H, -K, and -W and of their TRIM28 repressor in WBCs from celiac children and age-matched control subjects. A PCR real-time TaqMan amplification assay was used to evaluate HERV and TRIM28 transcripts with normalization of the results to glyceraldehyde-3-phosphate dehydrogenase. The RNA levels of pol genes of the three HERV families were significantly higher in WBCs from 38 celiac patients than from 51 control subjects. TRIM28 transcription was comparable between the two study populations.Conclusion: Present results show, for the first time, that pol genes of HERV-H, -K, and -W are overexpressed in patients with CD. Given their proinflammatory and autoimmune properties, this suggests that HERVs may contribute to the development of CD in susceptible individuals. What is Known:• Based on this, HERVs have been studied and proposed as contributing factors in various autoimmune disorders. What is New: • Present results show, for the first time, that pol genes of HERV-H, -K, and -W are overexpressed in patients with CD.

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Enhanced expression of human endogenous retroviruses in new-onset type 1 diabetes: Potential pathogenetic and therapeutic implications

Cited by 23 publications

References 48 publications

Coxsackievirus-B4 Infection Can Induce the Expression of Human Endogenous Retrovirus W in Primary Cells

Coxsackievirus-B4 Infection Can Induce the Expression of Human Endogenous Retrovirus W in Primary Cells

How Retroviruses and Retrotransposons in Our Genome May Contribute to Autoimmunity in Rheumatological Conditions

Overexpression of endogenous retroviruses in children with celiac disease

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