A tick-borne segmented RNA virus contains genome segments derived from unsegmented viral ancestors

Abstract

Although segmented and unsegmented RNA viruses are commonplace, the evolutionary links between these two very different forms of genome organization are unclear. We report the discovery and characterization of a tick-borne virus-Jingmen tick virus (JMTV)-that reveals an unexpected connection between segmented and unsegmented RNA viruses. The JMTV genome comprises four segments, two of which are related to the nonstructural protein genes of the genus Flavivirus (family Flaviviridae), whereas the remaining segments are unique to this virus, have no known homologs, and contain a number of features indicative of structural protein genes. Remarkably, homology searching revealed that sequences related to JMTV were present in the cDNA library from Toxocara canis (dog roundworm; Nematoda), and that shared strong sequence and structural resemblances. Epidemiological studies showed that JMTV is distributed in tick populations across China, especially Rhipicephalus and Haemaphysalis spp., and experiences frequent host-switching and genomic reassortment. To our knowledge, JMTV is the first example of a segmented RNA virus with a genome derived in part from unsegmented viral ancestors.evolution | segmentation S egmentation is a common form of genome organization in RNA viruses, although why it has evolved more than once and is maintained in such a diverse array of viruses, including those with both positive-and negative-sense genomes, are unclear (1). Segmented and unsegmented viruses usually belong to different viral families, such that the sequence divergence between them is often too great for any meaningful evolutionary inference. The only example of "recent" genome fragmentation in a single RNA molecule occurred in a laboratory strain of foot-and-mouth disease virus (2, 3), although that this occurred following extensive propagation in cell culture means that its relationship to segmentation in nature is uncertain. Hence, the evolutionary links between unsegmented and segmented viruses, as well as the mechanisms that underpin their genesis, are poorly understood.The Flaviviridae are a family of unsegmented positive sense RNA viruses that infect vertebrate and invertebrate species, including the important human pathogens dengue virus, yellow fever virus, and hepatitis C virus. Despite the substantial sequence divergence between the Flavivirus, Pestivirus, and Hepacivirus genera that make up the Flaviviridae, they exhibit a similar genomic structure characterized by a single ORF with distinct clusters of structural and nonstructural genes. The ORF is translated into a single polyprotein, which is subsequently cleaved by cellular and viral proteases into structural and nonstructural proteins. Among the nonstructural protein products, NS3 and NS5 possess the enzymatic domains essential for RNA capping and genome replication (4), whereas the NS3 and NS2b proteins form a two-component serine protease involved in posttranslational cleavage of the viral polyprotein (5).Herein we describe the discovery and characterization of an...

A Multicomponent Animal Virus Isolated from Mosquitoes

“…Occasionally though, more recent transitions are uncovered and analysis of these events provides insight into the macroevolution of RNA viruses. Qin et al (2014) reported just such a connection between segmented and unsegmented RNA viruses by describing a segmented virus (Jingmen tick virus, JMTV) with sequence homology to the Flaviviridae , a large family of vertebrate and invertebrate viruses (including a number of important human pathogens, e.g., Zika, yellow fever, West Nile, dengue, Japanese encephalitis and Hepatitis C viruses) with unsegmented, positive-sense RNA genomes.…”

Divergent Viruses Discovered in Arthropods and Vertebrates Revise the Evolutionary History of the Flaviviridae and Related Viruses

“…In addition, our understanding of arthropods has largely focused on their role as vectors for vertebrate viruses, although this view has recently been challenged by the discovery of phylogenetically divergent arthropod-specific viruses (3,4). The remaining genera in the family-Hepacivirus, Pegivirus, and Pestivirus-are exclusively found in mammals, and their diversity has greatly expanded with recent virus discoveries in various mammalian species, including bats, dogs, horses, pigs, ruminants, and rodents (5)(6)(7)(8)(9)(10)(11)(12)(13).…”

“…Although GKaV was reported to be a double-stranded RNA (dsRNA) virus (14), the RNA digestion experiment was performed on crude plant extracts where the dsRNA is more likely to be the replication complex rather than the genome itself (15). More remarkable was the recent demonstration that Jingmen tick virus (JMTV) and Toxocara canis larva agent (TCLA) are clearly related to flaviviruses but possess a very different genomic plan comprising four distinct segments (11), in turn raising questions about the evolutionary link between segmented and unsegmented genomes. Since these segmented flavi-like viruses have not been formally classified, we tentatively refer to them as the Jingmenvirus group.…”

High-Resolution Metatranscriptomics Reveals the Ecological Dynamics of Mosquito-Associated RNA Viruses in Western Australia

“…Although these insect-specific viruses have no direct impact on public health, they may modulate the transmission of viruses that are pathogenic to vertebrates (3). The development of metagenomic sequencing approaches has therefore led to a reevaluation of the mosquito virome, including the recent discovery of viruses of the families Bunyaviridae (4)(5)(6)(7)(8), Rhabdoviridae (6,(9)(10)(11), Orthomyxoviridae (6,12), Flaviviridae (13)(14)(15), Mesoniviridae (16), and Reoviridae (8,17) as well as of the unclassified Chuvirus (6) and Negevirus (18) groups. In addition, metagenomics surveys have discovered viruses in families not previously known to infect mosquitoes, such as the Iflaviridae, Dicistroviridae, Totiviridae, Chrysoviridae, and Narnaviridae (8,(19)(20)(21)(22).…”