Excess Type I Interferon Signaling in the Mouse Seminiferous Tubules Leads to Germ Cell Loss and Sterility

Satie, Anne‐Pascale; Mazaud-Guittot, Séverine; Seif, Isabelle; Mahé, Dominique; He, Zhiguo; Jouve, G; Jégou, Bernard; Dejucq-Rainsford, Nathalie

doi:10.1074/jbc.m111.229120

Cited by 29 publications

(33 citation statements)

References 62 publications

(59 reference statements)

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“…Further, while an antiviral effect of RNA interference has been detected in certain mammalian systems (Li et al 2013b), it is considered to have been largely superseded in mammalian antiviral innate immunity by type I interferons (Cullen et al 2013;Cullen 2014). However, overexpression of interferon α prevents germ-cell development in mice and its receptor is not expressed on pachytene spermatocytes (Satie et al 2011), perhaps censoring this antiviral mechanism in the germline (Pare and Sullivan 2014).…”

Section: Discussionmentioning

confidence: 99%

piRNAs derived from ancient viral processed pseudogenes as transgenerational sequence-specific immune memory in mammals

Parrish

Fujino

Shiromoto

et al. 2015

RNA

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Endogenous bornavirus-like nucleoprotein elements (EBLNs) are sequences within vertebrate genomes derived from reverse transcription and integration of ancient bornaviral nucleoprotein mRNA via the host retrotransposon machinery. While species with EBLNs appear relatively resistant to bornaviral disease, the nature of this association is unclear. We hypothesized that EBLNs could give rise to antiviral interfering RNA in the form of PIWI-interacting RNAs (piRNAs), a class of small RNA known to silence transposons but not exogenous viruses. We found that in both rodents and primates, which acquired their EBLNs independently some 25-40 million years ago, EBLNs are present within piRNA-generating regions of the genome far more often than expected by chance alone (P = 8 × 10 −3 -6 × 10 −8 ). Three of the seven human EBLNs fall within annotated piRNA clusters and two marmoset EBLNs give rise to bona fide piRNAs. In both rats and mice, at least two of the five EBLNs give rise to abundant piRNAs in the male gonad. While no EBLNs are syntenic between rodent and primate, some of the piRNA clusters containing EBLNs are; thus we deduce that EBLNs were integrated into existing piRNA clusters. All true piRNAs derived from EBLNs are antisense relative to the proposed ancient bornaviral nucleoprotein mRNA. These observations are consistent with a role for EBLN-derived piRNA-like RNAs in interfering with ancient bornaviral infection. They raise the hypothesis that retrotransposon-dependent virus-to-host gene flow could engender RNA-mediated, sequence-specific antiviral immune memory in metazoans analogous to the CRISPR/Cas system in prokaryotes.

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Section: Discussionmentioning

confidence: 99%

piRNAs derived from ancient viral processed pseudogenes as transgenerational sequence-specific immune memory in mammals

Parrish

Fujino

Shiromoto

et al. 2015

RNA

View full text Add to dashboard Cite

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“…438,441,442,450,451 In the testis, activation of TLR3 increases interferon production and interferon-inducible genes involved in viral protection in Sertoli cells, Leydig cells, and even spermatogenic cells. [438][439][440]450,451,597 Interferon production may also be induced through activation of TLR4. Testicular macrophages produce type 1 interferons constitutively, but viral infections upregulate their expression in both macrophages and somatic cells of the testis.…”

Section: Interferonsmentioning

confidence: 99%

The Immunophysiology of Male Reproduction

Hedger

2015

Knobil and Neill's Physiology of Reproduction

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“…These factors could explain why expression of hIFN-α did not have obvious adverse effects on transgenic calves in our study. This is supported by a report in which transgenic mice expressing IFN-β (which belongs to the same IFN family as IFN-α) displayed similar behavior, external anatomy, life span, and female fertility as wild type mice, although male transgenic mice displayed reduced fertility [10]. The idiopathic infertilities may be caused by IFNs in the extracellular fluid, which affect the interplay between germ cells and Sertoli cells [22].…”

Section: Discussionmentioning

confidence: 64%

Expression of Intracellular Interferon-Alpha Confers Antiviral Properties in Transfected Bovine Fetal Fibroblasts and Does Not Affect the Full Development of SCNT Embryos

Zhang

et al. 2014

PLoS ONE

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Foot-and-mouth disease, one of the most significant diseases of dairy herds, has substantial effects on farm economics, and currently, disease control measures are limited. In this study, we constructed a vector with a human interferon-α (hIFN-α) (without secretory signal sequence) gene cassette containing the immediate early promoter of human cytomegalovirus. Stably transfected bovine fetal fibroblasts were obtained by G418 selection, and hIFN-α transgenic embryos were produced by somatic cell nuclear transfer (SCNT). Forty-six transgenic embryos were transplanted into surrogate cows, and five cows (10.9%) became pregnant. Two male cloned calves were born. Expression of hIFN-α was detected in transfected bovine fetal fibroblasts, transgenic SCNT embryos, and different tissues from a transgenic SCNT calf at two days old. In transfected bovine fetal fibroblasts, expression of intracellular IFN-α induced resistance to vesicular stomatitis virus infection, increased apoptosis, and induced the expression of double-stranded RNA-activated protein kinase gene (PKR) and the 2′-5′-oligoadenylate synthetase gene (2′-5′ OAS), which are IFN-inducible genes with antiviral activity. Analysis by qRT-PCR showed that the mRNA expression levels of PKR, 2′-5′ OAS, and P53 were significantly increased in wild-type bovine fetal fibroblasts stimulated with extracellular recombinant human IFN-α-2b, showing that intracellular IFN-α induces biological functions similar to extracellular IFN-α. In conclusion, expression of intracellular hIFN-α conferred antiviral properties in transfected bovine fetal fibroblasts and did not significantly affect the full development of SCNT embryos. Thus, IFN-α transgenic technology may provide a revolutionary way to achieve elite breeding of livestock.

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Excess Type I Interferon Signaling in the Mouse Seminiferous Tubules Leads to Germ Cell Loss and Sterility

Cited by 29 publications

References 62 publications

piRNAs derived from ancient viral processed pseudogenes as transgenerational sequence-specific immune memory in mammals

piRNAs derived from ancient viral processed pseudogenes as transgenerational sequence-specific immune memory in mammals

The Immunophysiology of Male Reproduction

Expression of Intracellular Interferon-Alpha Confers Antiviral Properties in Transfected Bovine Fetal Fibroblasts and Does Not Affect the Full Development of SCNT Embryos

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