PMID- 21931546 OWN - NLM STAT- MEDLINE DCOM- 20120130 LR - 20231105 IS - 1553-7374 (Electronic) IS - 1553-7366 (Linking) VI - 7 IP - 9 DP - 2011 Sep TI - Discovery of the first insect nidovirus, a missing evolutionary link in the emergence of the largest RNA virus genomes. PG - e1002215 LID - 10.1371/journal.ppat.1002215 [doi] AB - Nidoviruses with large genomes (26.3-31.7 kb; 'large nidoviruses'), including Coronaviridae and Roniviridae, are the most complex positive-sense single-stranded RNA (ssRNA+) viruses. Based on genome size, they are far separated from all other ssRNA+ viruses (below 19.6 kb), including the distantly related Arteriviridae (12.7-15.7 kb; 'small nidoviruses'). Exceptionally for ssRNA+ viruses, large nidoviruses encode a 3'-5'exoribonuclease (ExoN) that was implicated in controlling RNA replication fidelity. Its acquisition may have given rise to the ancestor of large nidoviruses, a hypothesis for which we here provide evolutionary support using comparative genomics involving the newly discovered first insect-borne nidovirus. This Nam Dinh virus (NDiV), named after a Vietnamese province, was isolated from mosquitoes and is yet to be linked to any pathology. The genome of this enveloped 60-80 nm virus is 20,192 nt and has a nidovirus-like polycistronic organization including two large, partially overlapping open reading frames (ORF) 1a and 1b followed by several smaller 3'-proximal ORFs. Peptide sequencing assigned three virion proteins to ORFs 2a, 2b, and 3, which are expressed from two 3'-coterminal subgenomic RNAs. The NDiV ORF1a/ORF1b frameshifting signal and various replicative proteins were tentatively mapped to canonical positions in the nidovirus genome. They include six nidovirus-wide conserved replicase domains, as well as the ExoN and 2'-O-methyltransferase that are specific to large nidoviruses. NDiV ORF1b also encodes a putative N7-methyltransferase, identified in a subset of large nidoviruses, but not the uridylate-specific endonuclease that - in deviation from the current paradigm - is present exclusively in the currently known vertebrate nidoviruses. Rooted phylogenetic inference by Bayesian and Maximum Likelihood methods indicates that NDiV clusters with roniviruses and that its branch diverged from large nidoviruses early after they split from small nidoviruses. Together these characteristics identify NDiV as the prototype of a new nidovirus family and a missing link in the transition from small to large nidoviruses. FAU - Nga, Phan Thi AU - Nga PT AD - Department of Virology, National Institute of Hygiene and Epidemiology, Hanoi, Vietnam. FAU - Parquet, Maria del Carmen AU - Parquet Mdel C FAU - Lauber, Chris AU - Lauber C FAU - Parida, Manmohan AU - Parida M FAU - Nabeshima, Takeshi AU - Nabeshima T FAU - Yu, Fuxun AU - Yu F FAU - Thuy, Nguyen Thanh AU - Thuy NT FAU - Inoue, Shingo AU - Inoue S FAU - Ito, Takashi AU - Ito T FAU - Okamoto, Kenta AU - Okamoto K FAU - Ichinose, Akitoyo AU - Ichinose A FAU - Snijder, Eric J AU - Snijder EJ FAU - Morita, Kouichi AU - Morita K FAU - Gorbalenya, Alexander E AU - Gorbalenya AE LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110908 PL - United States TA - PLoS Pathog JT - PLoS pathogens JID - 101238921 RN - 0 (RNA, Viral) RN - EC 3.1.- (Exoribonucleases) SB - IM MH - Amino Acid Sequence MH - Animals MH - Base Sequence MH - *Biological Evolution MH - Cell Line MH - Cloning, Molecular MH - Computational Biology MH - Culex/*virology MH - Exons MH - Exoribonucleases/genetics MH - Gene Expression Regulation, Viral MH - Genes, Viral MH - Genome Size MH - Molecular Sequence Data MH - Nidovirales/*classification/*genetics/physiology MH - Nucleic Acid Conformation MH - Open Reading Frames/genetics MH - Phylogeny MH - RNA, Viral/*genetics MH - Sequence Alignment MH - Sequence Analysis, DNA MH - Vietnam MH - Virus Replication PMC - PMC3169540 EDAT- 2011/09/21 06:00 MHDA- 2012/01/31 06:00 CRDT- 2011/09/21 06:00 PHST- 2011/03/15 00:00 [received] PHST- 2011/06/28 00:00 [accepted] PHST- 2011/09/21 06:00 [entrez] PHST- 2011/09/21 06:00 [pubmed] PHST- 2012/01/31 06:00 [medline] AID - PPATHOGENS-D-11-00548 [pii] AID - 10.1371/journal.ppat.1002215 [doi] PST - ppublish SO - PLoS Pathog. 2011 Sep;7(9):e1002215. doi: 10.1371/journal.ppat.1002215. Epub 2011 Sep 8.