Equine Torovirus (BEV) Induces Caspase-Mediated Apoptosis in Infected Cells

Toroviruses are gastroenteritis causing agents that infect different animal species and humans. To date, very little is known about how toroviruses cause disease. Here, we describe for the first time that the prototype member of this genus, the equine torovirus Berne virus (BEV), induces apoptosis in infected cells at late times postinfection. Observation of BEV infected cells by electron microscopy revealed that by 24 hours postinfection some cells exhibited morphological characteristics of apoptotic cells. Based on this finding, we analyzed several apoptotic markers, and observed protein synthesis inhibition, rRNA and DNA degradation, nuclear fragmentation, caspase-mediated cleavage of PARP and eIF4GI, and PKR and eIF2α phosphorylation, all these processes taking place after peak virus production. We also determined that both cell death receptor and mitochondrial pathways are involved in the apoptosis process induced by BEV. BEV-induced apoptosis at late times postinfection, once viral progeny are produced, could facilitate viral dissemination in vivo and contribute to viral pathogenesis

Rotavirus NSP1 Inhibits NFκB Activation by Inducing Proteasome-Dependent Degradation of β-TrCP: A Novel Mechanism of IFN Antagonism

Mechanisms by which viruses counter innate host defense responses generally involve inhibition of one or more components of the interferon (IFN) system. Multiple steps in the induction and amplification of IFN signaling are targeted for inhibition by viral proteins, and many of the IFN antagonists have direct or indirect effects on activation of latent cytoplasmic transcription factors. Rotavirus nonstructural protein NSP1 blocks transcription of type I IFNα/β by inducing proteasome-dependent degradation of IFN-regulatory factors 3 (IRF3), IRF5, and IRF7. In this study, we show that rotavirus NSP1 also inhibits activation of NFκB and does so by a novel mechanism. Proteasome-mediated degradation of inhibitor of κB (IκBα) is required for NFκB activation. Phosphorylated IκBα is a substrate for polyubiquitination by a multisubunit E3 ubiquitin ligase complex, Skp1/Cul1/F-box, in which the F-box substrate recognition protein is β-transducin repeat containing protein (β-TrCP). The data presented show that phosphorylated IκBα is stable in rotavirus-infected cells because infection induces proteasome-dependent degradation of β-TrCP. NSP1 expressed in isolation in transiently transfected cells is sufficient to induce this effect. Targeted degradation of an F-box protein of an E3 ligase complex with a prominent role in modulation of innate immune signaling and cell proliferation pathways is a unique mechanism of IFN antagonism and defines a second strategy of immune evasion used by rotaviruses

The αGal Epitope of the Histo-Blood Group Antigen Family Is a Ligand for Bovine Norovirus Newbury2 Expected to Prevent Cross-Species Transmission

Among Caliciviridae, the norovirus genus encompasses enteric viruses that infect humans as well as several animal species, causing gastroenteritis. Porcine strains are classified together with human strains within genogroup II, whilst bovine norovirus strains represent genogroup III. Various GI and GII human strains bind to carbohydrates of the histo-blood group family which may be shared among mammalian species. Genetic relatedness of human and animal strains as well as the presence of potentially shared ligands raises the possibility of norovirus cross-species transmission. In the present study, we identified a carbohydrate ligand for the prototype bovine norovirus strain Bo/Newbury2/76/UK (NB2). Attachment of virus-like particles (VLPs) of the NB2 strain to bovine gut tissue sections showed a complete match with the staining by reagents recognizing the Galα1,3 motif. Alpha-galactosidase treatment confirmed involvement of a terminal alpha-linked galactose. Specific binding of VLPs to the αGal epitope (Galα3Galβ4GlcNAcβ-R) was observed. The binding of Galα3GalαOMe to rNB2 VLPs was characterized at atomic resolution employing saturation transfer difference (STD) NMR experiments. Transfection of human cells with an α1,3galactosyltransferase cDNA allowed binding of NB2 VLPs, whilst inversely, attachment to porcine vascular endothelial cells was lost when the cells originated from an α1,3galactosyltransferase KO animal. The αGal epitope is expressed in all mammalian species with the exception of the Hominidaea family due to the inactivation of the α1,3galactosyltransferase gene (GGTA1). Accordingly, the NB2 carbohydrate ligand is absent from human tissues. Although expressed on porcine vascular endothelial cells, we observed that unlike in cows, it is not present on gut epithelial cells, suggesting that neither man nor pig could be infected by the NB2 bovine strain

Teknologia-alustasta innovaatioekosysteemiksi

Platform businesses are disrupting and transforming industries. With platform businesses, the value creation process shifts from relying on companies’ internal resources to harnessing resources from ecosystems. This kind of new value creation system has been argued to be the key driver for the success of platforms. Technology companies are currently opening some of their boundary resources: the access to some of the functionalities of their key technologies. These open interfaces invite companies to co-create new digital innovations and build their own complementary solutions on top of the key technology. Thus, the innovation ecosystem becomes the most valuable asset for platform companies. However, building an ecosystem is one of the biggest challenges for platform owners. The main questions are 1) how to attract diverse actors to the platform and 2) how to engage them to co-creation of value. Even though platforms have been widely studied in different literature streams, the formation and evolution of innovation ecosystems around platforms have remained unexplored. The motivation for this thesis is to increase the understanding how innovation ecosystems emerge around platforms and how the platform owner can facilitate the co-creation of innovation in its platform. The empirical part of this thesis presents a comparative case study of two innovation ecosystems that are forming around a technology platform. Research data was collected through semi-structured interviews with potential members of the ecosystems and with the representatives of the platform owner organization. Data analysis was conducted in an iterative process that included transcription, coding and categorization of the data as well as comparison of the two cases. Since no previous literature exists specifically on formation of innovation ecosystems around technology platforms, the empirical study is supported with a comprehensive literature review on platforms as well as evolution and management of innovation networks. As a result, this thesis presents new theoretical framework on factors that support the emergence of an innovation ecosystem around a technology platform. The findings suggest that a platform owner should create a clear vision of the platform and industry evolution. In addition, organizational culture that embraces open innovation as well as flexible organizational processes support the collaboration in the ecosystem. Understanding partners’ diverse motivations of joining the ecosystem supports platform owners to design the platform and ecosystem activities as attractive as possible for potential platform contributors. Furthermore, building and managing ecosystem relationships becomes a strategic competence for platform owners, in order to accelerate the early-growth of ecosystems. Thus, in addition to platform design, platform owners should also focus on ecosystem orchestration processes in order to support the value creation and equitable value capture in the ecosystem.Digitaalisten alustojen kehitys on radikaalisti muuttanut kilpailua perinteisillä toimialoilla. Alustat mahdollistavat uudenlaisen arvonluonnin, jossa yritysten fokus siirtyy organisaation omien resurssien koordinoimisesta kokonaisten ekosysteemien resurssien hyödyntämiseen. Tällä hetkellä teknologiayritykset ovatkin avaamassa rajapintojaan yritysten keskeisten teknologioiden ympärille, mikä houkuttelee kolmansia osapuolia luomaan omia komplementaarisia innovaatioitaan alustan päälle. Näin muodostuvista innovaatio- ekosysteemeistä onkin tullut kaikista arvokkain voimavara alustan omistajille. Ekosysteemien rakentaminen on kuitenkin yksi suurimpia haasteita alustojen omistajille. Alustan omistajan tuleekin keskittyä 1) houkuttelemaan erilaisia toimijoita alustalle ja 2) tukemaan toimijoita arvonluonnin yhteiskehittämisessä. Vaikka alustoja on tutkittu laajalti kirjallisuudessa, innovaatioekosysteemien muodostuminen teknologia-alustojen ympärille on tutkimusaiheena uusi ja vaatii lisää tutkimusta. Tämän työn tavoitteena on lisätä ymmärrystä innovaatioekosysteemin muodostumisesta teknologia-alustojen ympärille ja selvittää, miten alustan omistaja voi tukea arvonluontia alustalla. Tutkimuksen empiirinen osuus toteutettiin tapaustutkimuksena, jossa tutkittiin kahden innovaatioekosysteemin muodostumista teknologia-alustan ympärille. Tutkimusaineisto kerättiin haastattelemalla ekosysteemien jäseniä ja alustan omistajaa. Lisäksi havainnointia hyödynnettiin aineistonkeruussa. Datan analysointi toteutettiin iteratiivisena prosessina, johon kuului aineiston litterointi, koodaus, kategorisointi ja ekosysteemien tuloksien vertailu. Koska tutkimusaiheesta ei löytynyt aiempaa kirjallisuutta, tutkimuksen teoriapohjana on laaja kirjallisuuskatsaus alustoista sekä innovaatioverkostojen muodostumisesta ja koordinoinnista. Tutkimuksen tulos on uusi teoreettisen viitekehys tekijöistä, jotka tukevat innovaatioekosysteemin muodostumista teknologia-alustan ympärille. Tulosten mukaan alustan omistajan tulisi luoda selkeä visio alustasta. Lisäksi organisaatiokulttuuri, joka tukee avointa innovaatiota sekä joustavat ja läpinäkyvät prosessit edistävät yhteistyön kehittymistä ekosysteemissä. Potentiaalisten ekosysteemin jäsenten erilaisten motivaatioiden ymmärtäminen puolestaan auttaa alustan omistajaa suunnittelemaan teknologia-alustan ja ekosysteemin aktiviteetit mahdollisimman houkuttelevaksi potentiaalisille jäsenille. Tutkimus osoittaa myös, että ekosysteemin suhteiden luominen ja ylläpitäminen ovat strategisia kyvykkyyksiä. Alustan teknisen arkkitehtuurin lisäksi alustan omistajan tulisi siten myös keskittyä yhteistyön kehittämiseen ekosysteemissä