Table 1.
Whole viral genome studies by SHAPE.
| Virus Family/Genus | Virus Species | Ref. | Summary Statement |
|---|---|---|---|
| Retroviridae/Lentivirus | Human immunodeficiency virus (HIV-1) | (75) | The first whole viral genome interrogated by SHAPE reveals extensive secondary structure elements throughout the genome, many of which are functionally important for HIV-1. |
| Simian immunodeficiency virus (SIVmac239), HIV-1 | (76) | Many RNA structures previously identified in HIV-1 coding regions (75) are not conserved in the related SIVmac239 (~50% sequence similarity). | |
| HIV-1 | (37) | New SHAPE-MaP analysis strategy supports a refined genome structure model; low SHAPE/low Shannon entropy genome regions identify novel functional elements. | |
| SIVcpzMB897, SIVmac239, HIV-1 | (79) | Correlation of SHAPE reactivity patterns across the genomes of three lentivirus species pinpoint multiple novel functional structural elements. | |
| Picornaviridae/Enterovirus | Poliovirus | (78) | Second human virus family interrogated by SHAPE identifies novel functional elements, including the 3Dpol RNA element which may mediate an interaction with the viral 3Cpro protein. |
| Flaviviridae/Hepacivirus | Hepatitis C virus (HCV) | (65) | SHAPE analyses of genomes of three HCV genotypes reveals many conserved highly structured regions, including four novel conserved structures required for optimal viral fitness. |
| (69) | SHAPE-derived RNA structure models melded with covariation models identifies novel conserved stem-loops across the HCV genome, including four motifs required for viral fitness. | ||
| Togaviridae/Alphavirus | Sindbis virus (SINV), Venezuelan equine encephalitis virus (VEEV) | (73) | Structure-first SHAPE analysis identifies functional RNA elements only present in individual alphavirus species, and not detectable by covariation and comparative structure analyses. |
| Flaviviridae/Flavivirus | Dengue virus 2, (DENV2) | (58) | Higher order RNA tertiary structures are pervasive across the DENV2 genome, and promote a compact global genome architecture and enhance viral fitness. |
| DENV1, DENV2, DENV3, DENV4, Zika Virus (ZIKV) | (74) | Highly structured regions are conserved across four DENV serotypes and four ZIKV strains, and five long-range ZIKV RNA-RNA interactions are important for viral fitness. | |
| ZIKV | (72) | A long-range RNA-RNA interaction between sequences in the 5′-UTR and the Env-coding region occurs exclusively in epidemic ZIKV strains and is important for viral fitness. | |
| Orthomyxoviridae/ Alphainfluenzavirus | Influenza A Virus (IAV) | (64) | Inter-segment interactions between the eight IAV genomic segments are both redundant and important for viral packaging and growth. |
| IAV Segments 8, 7, 5(+) | (68, 70, 71) | IAV RNA genome segments 7 and 8 form highly structured conserved domains. Single-stranded regions in segment 5(+) can be targeted with antisense oligonucleotides to inhibit replication. | |
| Tombusviridae/Tombusvirus | Tomato bushy stunt virus (TBSV) | (63) | SHAPE and atomic force microscopy reveal a compact genome structure; local RNA structures provide a structural scaffold for the formation of functional long-range interactions. |
| Bromoviridae/Cucumovirus | Cucumber mosaic virus (CMV) Segment 3 | (81) | Covariation analysis of SHAPE-defined structures identifies four novel functional structural elements; SHAPE analysis in infected cell lysate reveals a protein binding site. |
| Plant satellite virus Virgaviridae/Tobamovirus | Satellite-Tobacco mosaic virus (STMV) | (62, 77, 80) | SHAPE-directed genome structure models from independent groups are in excellent agreement, revealing a three-domain genome architecture where each domain corresponds to a viral function. |
| Plant satellite virus Tombusviridae/Carmovirus | Satellite-Turnip crinkle virus | (66) | SHAPE structure probing of this 356-nt satellite viral genome identifies an extended functional hairpin, H2. |
| Plant satellite virus Tombusviridae/Tombusvirus | Satellite-Cymbidium ringspot virus | (67) | SHAPE structure probing of this 619-nt satellite viral genome identifies several functional genome secondary and tertiary structures, including an RNA switch. |
Studies are listed chronologically by date within each genus in the order: human viruses, plant viruses, and satellite viruses; with studies of whole genomes preceding genome segments.