Endogenous bornavirus elements in eukaryotes and the usage

Endogenous bornavirus elements in eukaryotes and the usage of them in antiviral immunity Heleri Kirsip Bioinformaatika JC 10. 11. 2016

Mis on endogeenne viiruslik element (EVE)? • Endogeensed viiruslikud elemendid – viiruse genoom, geenid või geenide tükid, mis on integreerunud organismi genoomi ning fikseerunud põlvkondade jooksul (Bejarno et al. , 1996).

Endogenous bornavirus-like elements • (-)ss. RNA, Mononegavirales, Bornaviridae • EBLs (endogenous bornavirus-like elements) • Nucleoprotein • • EBLN Via LINE-1 element • Borna disease virus (BDV) • Antiviral immunity with EBLN elements

Katzourakis and Gifford, 2010

it. EBLNs and hs. EBLNs • • Ictidomys tridecemlineatus (TLS) Intact ORF 77% aminoacid identity Predicted transcripts present in several tissue samples from both breeding and wildcaptured TLSs by RTPCR • Human • Intact ORF • 41% aminoacid identity • Transcripts are expressed as RNA in several tissues

it. EBLNs and hs. EBLNs • • it. EBLN Co-localizes with the viral factory in the nucleus Decreases exogenous BDV infection and replication Incorporated into the viral ribonucleoproteins • • hs. EBLN • Exogenous BDV infection and replication remains the same • Is not incorporated into viral ribonucleoproteins Localizes in the cytoplasm

Dominant negative forms of viral proteins.

Transcript reversion with anamnestic pi. RNA silencing (TRAPS) • Marmoset EBLN • mm. EBLN/rn. EBL N • 1 within annotated pi. RNA • 2 (3) within • hs. EBLN • 3 within clusters • *hs. EBLN-7 – pi. RNA like RNA (shorter) clusters • *cj. EBLN-7 – pi. RNA like RNA (shorter) annotated pi. RNA clusters

• • • Transcript reversion with anamnestic pi. RNA silencing (TRAPS) Mus musculus (mm. EBLN) Expressed as RNA in at least one tissue (all 7 human EBLN elements, 2 mm. EBLN) Within PIWI-interacting RNA (pi. RNA)-generating loci – “pi. RNA clusters” EBLNs expressed as pi. RNAs EBLN-derives pi. RNAs mapped to the antisense strand relative to bornavirus N m. RNA Post-transcriptionally silencing Parrish et al. , 2015

Transcript reversion with anamnestic pi. RNA silencing (TRAPS)

lnc. RNA immunity • Human (hs. EBLN) • hs. EBLN may affect the expression of its neighbouring COMMD 3 gene (downregulated) • Protein locates in cytoplasm – long non-coding RNA (lnc. RNA) • COMMD 3 – NFκB pathway – counteract invading pathogens

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