Use of <em>In vivo</em> Imaging to Monitor the Progression of Experimental Mouse Cytomegalovirus Infection in Neonates

Human Cytomegalovirus (HCMV or HHV-5) is a life-threatening  pathogen in immune-compromised individuals. Upon congenital or neonatal  infection, the virus ...

université de strasbourg

Regulation of gene expression by microRNAs (miRNAs) is now considered as an essential mechanism for cell development and homeostasis. Indeed, numerous studies have reported that modulating their expression, maturation, or activity can affect cell survival, identity or activation. In particular, miRNAs are key players in the tight regulation of signaling cascades, and as such, they appear as perfectly suited immunomodulators. Several immune-related processes, including inflammation, have recently been demonstrated to require specific miRNAs. In addition, the discovery of herpesvirus-encoded miRNAs has reinforced this assumption. To decipher the potential roles of miRNAs in innate antiviral immune response, we developed an in vivo model based on the inoculation of mouse cytomegalovirus (MCMV) in mice. Furthermore, we exploited a mouse line carrying a hypomorphic mutation in the Dicer gene to visualize the impact of impaired miRNA biogenesis upon the anti-MCMV response. Our data indicate that miRNAs are important actors in mounting an efficient response against herpesviruses. We suggest that a rapid and transient interferon response following viral infection requires miRNA-dependent repressor release. In addition, our in vivo efforts identified several miRNA targets, thus providing a conceptual framework for future analyzes on the regulation of specific actors involved in the Type I interferon pathway.

Deregulation of type I IFN-dependent genes correlates with increased susceptibility to cytomegalovirus acute infection of dicer mutant mice.

R&eacute;gulation de l&#39;expression g&eacute;nique de microARN (miARN) est maintenant consid&eacute;r&eacute;e comme un m&eacute;canisme essentiel pour le d&eacute;veloppement des cellules et l&#39;hom&eacute;ostasie. En effet, de nombreuses &eacute;tudes ont signal&eacute; que modulation de leur expression, maturation ou activit&eacute; peut affecter la survie des cellules, identit&eacute; ou activation. En particulier, les miARN est des acteurs cl&eacute;s dans la r&eacute;gulation serr&eacute;e des cascades de signalisation, et &agrave; ce titre, ils apparaissent comme des immunomodulateurs parfaitement adapt&eacute;s. Plusieurs processus immunitaire li&eacute;s, notamment : inflammation, ont r&eacute;cemment &eacute;t&eacute; d&eacute;montr&eacute;s d&#39;exiger des miARN sp&eacute;cifique. En outre, la d&eacute;couverte des miARN herp&egrave;svirus cod&eacute; a renforc&eacute; cette hypoth&egrave;se. Pour d&eacute;chiffrer les r&ocirc;les possibles des miARN dans la r&eacute;ponse immunitaire antivirale inn&eacute;e, nous avons d&eacute;velopp&eacute; un mod&egrave;le in vivo, bas&eacute; sur l&#39;inoculation du cytom&eacute;galovirus souris (MCMV) chez la souris. En outre, nous avons exploit&eacute; une lign&eacute;e de souris porteuses d&#39;une mutation de hypomorphic dans le g&egrave;ne Dicer de visualiser l&#39;impact de la biogen&egrave;se miRNA avec facult&eacute;s affaiblies sur la r&eacute;action anti-MCMV. Nos donn&eacute;es indiquent que les miARN est des acteurs importants dans le montage d&#39;une r&eacute;ponse efficace contre le virus de l&#39;herp&egrave;s. Nous sugg&eacute;rons qu&#39;une r&eacute;ponse rapide et transitoire de l&#39;interf&eacute;ron apr&egrave;s une infection virale n&eacute;cessite lib&eacute;ration r&eacute;presseur de miRNA-d&eacute;pendante. En outre, nos efforts in vivo a identifi&eacute; plusieurs cibles de miRNA, offrant ainsi un cadre conceptuel pour l&#39;avenir analyse sur la r&eacute;gulation des acteurs sp&eacute;cifiques impliqu&eacute;s dans le Type I voie interf&eacute;ron.

D&eacute;r&eacute;glementation du type j&#39;ai corr&eacute;lats de g&egrave;nes IFN-d&eacute;pendante avec une sensibilit&eacute; accrue aux infections aigu&euml;s cytom&eacute;galovirus des souris mutantes dicer.

Regolazione dell&#39;espressione genica di microRNA (miRNAs) &egrave; ora considerato come un meccanismo essenziale per lo sviluppo delle cellule e l&#39;omeostasi. Infatti, numerosi studi hanno riportato che modulando la loro espressione, maturazione o attivit&agrave; pu&ograve; influenzare la sopravvivenza delle cellule, identit&agrave; o attivazione. In particolare, miRNAs sono attori chiave nella regolazione stretta di cascate di segnalazione, e come tali, essi appaiono come gli immunomodulatori perfettamente adatti. Diversi processi correlati immunitario, tra cui l&#39;infiammazione, hanno recentemente dimostrati di richiedono miRNAs specifici. Inoltre, la scoperta di herpesvirus-codificato miRNAs ha rafforzato questa ipotesi. Per decifrare il ruolo potenziale di miRNAs nella risposta immunitaria innata antivirale, abbiamo sviluppato un modello in vivo basato sull&#39;inoculazione di citomegalovirus mouse (MCMV) nei topi. Inoltre, abbiamo sfruttato una linea di mouse che trasportano una mutazione hypomorphic nel gene della cubettatrice per visualizzare l&#39;impatto di miRNA alterata biogenesi sulla risposta anti-MCMV. I nostri dati indicano che i miRNAs sono importanti attori in una risposta efficace contro herpesvirus di montaggio. Consigliamo che una risposta rapida e transitoria interferone dopo infezione virale richiede rilascio repressor miRNA-dipendente. Inoltre, il nostro impegno in vivo identificato molti obiettivi di miRNA, fornendo cos&igrave; un quadro concettuale per futuro analizza il regolamento degli attori specifici coinvolti nel tipo I pathway di interferone.

La deregolamentazione del tipo I correla geni IFN-dipendente con maggiore suscettibilit&agrave; all&#39;infezione acuta da citomegalovirus di topi mutanti cubettatrice.

To evaluate whether miR-20a belonging to the cluster miR-17-92 is a negative regulator of inflammation in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) by modulating expression of apoptosis signal-regulating kinase (ASK) 1, a key component of the toll-like receptors 4 pathway, upstream of p38 mitogen-activated protein kinase.

MiR-20a regulates ASK1 expression and TLR4-dependent cytokine release in rheumatoid fibroblast-like synoviocytes.

Pour &eacute;valuer si miR-20 a, appartenant &agrave; la grappe miR-17-92 est un r&eacute;gulateur n&eacute;gatif de l&#39;inflammation dans la polyarthrite rhumato&iuml;de (PR) fibroblastes synoviaux (FLS) en modulant l&#39;expression de la kinase de signal-r&eacute;gulation de l&#39;apoptose (ASK) 1, un &eacute;l&eacute;ment cl&eacute; de la voie des r&eacute;cepteurs toll-like 4, en amont de p38 mitogen-activated protein kinase.

MiR-20 a r&eacute;gule l&#39;expression ASK1 et lib&eacute;ration de cytokines TLR4-d&eacute;pendante dans les fibroblastes synoviaux polyarthrite rhumato&iuml;de.

Per valutare se miR-20a appartenendo a cluster miR-17-92 &egrave; un regolatore negativo dell&#39;infiammazione nell&#39;artrite reumatoide (RA) del fibroblasto-simili sinoviociti (FLS) modulando l&#39;espressione della chinasi di segnale-regolazione del apoptosis (ASK) 1, un componente chiave del percorso recettori toll-like 4, a monte della chinasi di proteina mitogene-attivata p38.

Eleonore Ostermann

ImmunoRhumatologie Moléculaire,
INSERM UMR_S 1109,
Centre de Recherche d'Immunologie et d'Hématologie,
ImmunoRhumatologie Moléculaire, INSERM UMR_S 1109, Centre de Recherche d'Immunologie et d'Hématologie

université de strasbourg

Use of In vivo Imaging to Monitor the Progression of Experimental Mouse Cytomegalovirus Infection in Neonates

Eleonore Ostermann

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}ImmunoRhumatologie Moléculaire,INSERM UMR_S 1109,Centre de Recherche d'Immunologie et d'Hématologie,ImmunoRhumatologie Moléculaire, INSERM UMR_S 1109, Centre de Recherche d'Immunologie et d'Hématologie

université de strasbourg

Use of In vivo Imaging to Monitor the Progression of Experimental Mouse Cytomegalovirus Infection in Neonates

ImmunoRhumatologie Moléculaire,
INSERM UMR_S 1109,
Centre de Recherche d'Immunologie et d'Hématologie,
ImmunoRhumatologie Moléculaire, INSERM UMR_S 1109, Centre de Recherche d'Immunologie et d'Hématologie