PMID- 35379005 OWN - NLM STAT- MEDLINE DCOM- 20220429 LR - 20220602 IS - 2379-5042 (Electronic) IS - 2379-5042 (Linking) VI - 7 IP - 2 DP - 2022 Apr 27 TI - ADAR-Editing during Ostreid Herpesvirus 1 Infection in Crassostrea gigas: Facts and Limitations. PG - e0001122 LID - 10.1128/msphere.00011-22 [doi] LID - e00011-22 AB - Ostreid herpesvirus-1 (OsHV-1) RNAs are enzymatically modified by A-to-I conversions during the infection of Crassostrea gigas. The increase of ADAR1 expression and hyper-editing activity parallel to OsHV-1 RNAs suggests a functional connection between dsRNA editing and antiviral responses. We analyzed 87 RNA-seq data sets from immuno-primed, resistant, and susceptible oysters exposed to OsHV-1 to compare the ADAR hyper-editing levels on host and viral transcripts and trace hyper-editing on the oyster genes. Host RNAs were more hyper-edited than viral RNAs, despite the increased editing of viral RNAs in late infection phases. A set of genes, representing approximately 0.5% of the oyster transcriptome and including several tripartite motif-containing sequences, were constantly hyper-edited. Conversely, we identified genes involved in antiviral response, miRNA maturation, and epigenetic regulation that were hyper-edited in specific conditions only. Despite technical and biological bottlenecks that hamper the understanding of the bivalve "RNA editome," available tools and technologies can be adapted to bivalve mollusks. IMPORTANCE Ostreid herpesvirus-1 (OsHV-1) is a harmful pathogen of bivalve species, such as oysters. However, knowledge is lacking about host-virus interactions at the molecular level, hampering the possibility of a correct management of viral outbreaks and related massive mortalities. Notably, OsHV-1 transcripts are massively modified by host RNA editing enzyme during infection, resulting in multiple A-to-I variations along RNAs assuming double-strand conformations. The impact of these modifications on host transcripts is, however, not completely clear. Analyzing RNA-seq data of oysters infected with OsHV-1, we revealed that approximately 0.5% of the oyster transcriptome is always enzymatically modified by ADAR, whereas genes involved in antiviral response, miRNA maturation, and epigenetic regulation were hyper-edited in specific conditions only. Despite our results, relevant technical bottlenecks impair an accurate quantification of RNA editing events, making necessary an approach specifically dedicated to the progressive understanding of oyster "RNA editome." FAU - Rosani, Umberto AU - Rosani U AUID- ORCID: 0000-0003-0685-1618 AD - Department of Biology, University of Padova, Padova, Italy. FAU - Bortoletto, Enrico AU - Bortoletto E AD - Department of Biology, University of Padova, Padova, Italy. FAU - Montagnani, Caroline AU - Montagnani C AD - IHPE, CNRS, Ifremer, Universite Montpellier, Montpellier, France. FAU - Venier, Paola AU - Venier P AD - Department of Biology, University of Padova, Padova, Italy. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220405 PL - United States TA - mSphere JT - mSphere JID - 101674533 RN - 0 (Antiviral Agents) RN - 0 (MicroRNAs) RN - 0 (RNA, Viral) RN - Ostreid herpesvirus 1 SB - IM MH - Animals MH - Antiviral Agents MH - *Crassostrea/genetics MH - DNA Viruses MH - Epigenesis, Genetic MH - *MicroRNAs/genetics MH - RNA, Viral/genetics PMC - PMC9044936 OTO - NOTNLM OT - ADAR OT - ADAR1 OT - OsHV-1 OT - RNA editing OT - antiviral immunity OT - bivalve OT - hyper-editing OT - innate immunity OT - malacoherpesvirus OT - oyster COIS- The authors declare no conflict of interest. EDAT- 2022/04/06 06:00 MHDA- 2022/04/30 06:00 PMCR- 2022/04/05 CRDT- 2022/04/05 05:26 PHST- 2022/04/06 06:00 [pubmed] PHST- 2022/04/30 06:00 [medline] PHST- 2022/04/05 05:26 [entrez] PHST- 2022/04/05 00:00 [pmc-release] AID - 00011-22 [pii] AID - msphere.00011-22 [pii] AID - 10.1128/msphere.00011-22 [doi] PST - ppublish SO - mSphere. 2022 Apr 27;7(2):e0001122. doi: 10.1128/msphere.00011-22. Epub 2022 Apr 5.