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Convergent evolution of argonaute-2 slicer antagonism in two distinct insect RNA viruses
Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). (Hultmark)
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2012 (Engelska)Ingår i: PLoS Pathogens, ISSN 1553-7366, E-ISSN 1553-7374, Vol. 8, nr 8, artikel-id e1002872Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

RNA interference (RNAi) is a major antiviral pathway that shapes evolution of RNA viruses. We show here that Nora virus, a natural Drosophila pathogen, is both a target and suppressor of RNAi. We detected viral small RNAs with a signature of Dicer-2 dependent small interfering RNAs in Nora virus infected Drosophila. Furthermore, we demonstrate that the Nora virus VP1 protein contains RNAi suppressive activity in vitro and in vivo that enhances pathogenicity of recombinant Sindbis virus in an RNAi dependent manner. Nora virus VP1 and the viral suppressor of RNAi of Cricket paralysis virus (1A) antagonized Argonaute-2 (AGO2) Slicer activity of RNA induced silencing complexes pre-loaded with a methylated single-stranded guide strand. The convergent evolution of AGO2 suppression in two unrelated insect RNA viruses highlights the importance of AGO2 in antiviral defense.

Ort, förlag, år, upplaga, sidor
2012. Vol. 8, nr 8, artikel-id e1002872
Nationell ämneskategori
Cell- och molekylärbiologi
Identifikatorer
URN: urn:nbn:se:umu:diva-61306DOI: 10.1371/journal.ppat.1002872ISI: 000308558000047PubMedID: 22916019Scopus ID: 2-s2.0-84866182888OAI: oai:DiVA.org:umu-61306DiVA, id: diva2:565801
Tillgänglig från: 2012-11-08 Skapad: 2012-11-08 Senast uppdaterad: 2023-03-24Bibliografiskt granskad
Ingår i avhandling
1. Biology of a small RNA virus that infects Drosophila melanogaster
Öppna denna publikation i ny flik eller fönster >>Biology of a small RNA virus that infects Drosophila melanogaster
2016 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Drosophila melanogaster has been extensively used as a model organism to study diverse facets of biology, including host-pathogen interactions and the basic biology of its pathogens. I have used the fruit fly as a model to study elementary aspects of Nora virus biology, such as the role of the different proteins encoded by the virus genome. Nora virus, an enteric virus transmitted via the feca-oral route, does not cause any obvious pathology in the fly, although the infection is persistent. Nora virus genome consists of a positive strand RNA that is translated in four open reading frames (ORF).  Since sequence homology studies did not yield much information about the different Nora virus proteins, I have used the cDNA clone of the virus to construct mutants to identify the specific function of each protein. My results have shown that,

1) The protein(s) encoded by ORF 1 are crucial for the replication of the virus genome.

2) The C-terminus of the ORF 1-encoded protein (VP1), is an inhibitor to the RNAi pathway.

3) The transmembrane domain in the N-terminus of the ORF2-encoded protein (VP2) is important for the formation of Nora virus virions.

4) The ORF 3-encoded protein (VP3) forms α-helical trimers and this protein is essential for the stability of Nora virus capsid.                                                    

I have also performed RNA sequencing to investigate the transcriptional response of D. melanogaster in response to Nora virus infection and my results indicate that,                       

5) The upregulation of genes related to cellular stress and protein synthesis and the downregulation of basal digestive machinery, together with the induction of upd3, implies major gut epithelium damage and subsequent regeneration.

Ort, förlag, år, upplaga, sidor
Umeå: Umeå University, 2016. s. 52
Nyckelord
Nora virus, Drosophila melanogaster, virus biology, host-pathogen interaction
Nationell ämneskategori
Cell- och molekylärbiologi
Forskningsämne
molekylärbiologi
Identifikatorer
urn:nbn:se:umu:diva-127352 (URN)978-91-7601-593-3 (ISBN)
Disputation
2016-12-01, Hörsal 135, Byggnad 9A, Norrlands Universitetssjukhus, Umeå, 14:00 (Engelska)
Opponent
Handledare
Tillgänglig från: 2016-11-10 Skapad: 2016-11-09 Senast uppdaterad: 2018-06-09Bibliografiskt granskad

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Sadanandan, Sajna AEkström, Jens-OlaHultmark, Dan

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