Molecular Insights into the Flavivirus Replication Complex
Abstract
:1. Introduction
2. The Flavivirus Replication Cycle
3. Function and Formation of the Replication Organelle
3.1. Function
3.2. Biogenesis
3.2.1. Replication Organelle Curvature
3.2.2. Host Factors in Assembly
4. Architecture of the Replication Organelle
4.1. Structure, Composition and Arrangement
4.2. Convoluted Membranes
4.3. Host Factors in RC Function
5. Nonstructural Proteins
5.1. NS1
Viruses | PDB IDs | Remarks | Space Group | Ref. |
---|---|---|---|---|
DENV-1 | 4OIG | NS1 | C121 | [18] |
6WEQ | NS1 in complex with neutralising 2B7 Fab | P1211 | [58] | |
DENV-2 | 4O6B | NS1 | H3 | [49] |
6WER | NS1 in complex with neutralising 2B7 Fab | I4122 | [58] | |
7K93 | NS1 in complex with neutralising 2B7 single chain Fab variable region (scFv) | P212121 | ||
7BSC | C-terminal NS1 in complex with 1G5.3 Fab | P21221 | [59] | |
JEV | 5O19 | C-terminal NS1 | I212121 | [60] |
WNV | 4OIE | NS1 | P3121 | [18] |
4OII | NS1 In complex with neutralising 22NS1 Fab | C121 | ||
4O6C | NS1 | P3 | [49] | |
4O6D | NS1 | P321 | ||
YFV | 5YXA | C-terminal NS1 | P212121 | [61] |
ZIKV | 5GS6 | NS1 from 2015 Brazil strain | P4122 | [48] |
5IY3 | NS1 | C2221 | [62] | |
5K6K | NS1 | I222 | [17] | |
5X8Y | NS1 | C2221 | [63] | |
7BSD | C-terminal NS1 in complex with 1G5.3 Fab | P212121 | [59] |
5.2. NS2A
5.3. NS2B
5.4. NS3
Viruses | PDB IDs | Protease Active Site | Remarks | Ref. |
---|---|---|---|---|
DENV-4 | 2VBC | Open | Partial NS2B cofactor linked to NS3 via a G4SG4 linker | [16] |
2WHX | Open | Partial NS2B cofactor linked to NS3 via a G4SG4 linker | [86] | |
2WZQ | Open | Partial NS2B cofactor linked to NS3 via a G4SG4 linker, glycine insertion mutant between E173 and P174 | ||
5YVJ | Open | Partial NS2B cofactor linked to NS3 via a G4SG4 linker | [94] | |
5YVU | Closed | NS2B cofactor linked to NS3 via a G4SG4 linker, in complex with BPTI | ||
5YVV | Closed | NS2B cofactor linked to NS3 via a G4SG4 linker | ||
5YVW | Closed | Unlinked NS2B cofactor | ||
5YVY | Closed | Unlinked NS2B cofactor | ||
5YW1 | Closed | Unlinked NS2B cofactor, in complex with BPTI | ||
MVEV | 2WV9 | Open | Partial NS2B cofactor linked to NS3 via a G4SG4 linker | [87] |
5.5. NS4A
5.6. NS4B
5.7. NS5
Viruses | PDB IDs | Ligands | Remarks | Space Group | Ref. |
---|---|---|---|---|---|
DENV-3 | 4V0Q | SAH and Zn | Conformation 5 | P21212 | [115] |
4V0R | GTP, Mg, SAH and Zn | ||||
5DTO | M7G, Mg, SAH and Zn | [111] | |||
5CCV | SAH and Zn | [123] | |||
5JJR | Compound 29, SAH, Mg and Zn | [124] | |||
5JJS | Compound 27, SAH, Mg and Zn | ||||
DENV-2 | 5ZQK | SAM, Mg and Zn | Conformation 3 | P1211 | [15] |
6KR2 | SAH and Zn | Conformation 3 | P1211 | [118] | |
6KR3 | SAH and Zn | Conformation 4 | C2221 | ||
JEV | 4K6M | SAH and Zn | Conformation 1 | H3 | [119] |
YFV | 6QSN | SAH and Zn | Conformation 2 | P212121 | [121] |
ZIKV | 5TFR | SAH and Zn | Conformation 1 | P21212 | [125] |
5TMH | P22121 | [116] | |||
5U0B | P21212 | [117] | |||
5M2X | P212121 | [126] | |||
5M2Z | P65 | ||||
6I7P | P212121 |
6. Interaction Network within the Replication Complex
Virus | Protein: Residues | Protein: Residues | References |
---|---|---|---|
DENV | NS1 (G161, W168) | NS4A-2K-NS4B | [54] |
NS1: 30–180 | NS4A-2K-NS4B: 35–61 (Y41) | [57] | |
NS2B | NS3 | ||
NS3: Helicase Domain II and III | NS4B: 129–165 (Q134) | [106,134,135] | |
NS3: 566–585 (N570) | NS5: 320–341 (K330) | [138,139] | |
NS4A: 40–76 (L48, T54, L60) | NS4B: 84–146 | [140] | |
NS4B | NS4B | [102] | |
WNV | NS1 | NS4B | [55] |
NS2A | NS2B | [74] | |
NS2A | NS4A | [74] | |
NS2B | NS3 | [74] | |
NS2B | NS4A | [74] | |
NS2B | NS4B | [74] | |
NS3 | NS5 | [74] | |
NS4A | NS4B | [74] | |
JEV | NS2A | NS2B | [75] |
NS3 | NS5 | [141] | |
YFV | NS1 | NS4A | [56] |
7. The Viral RNA
7.1. The 5′ UTR
7.2. The 3′UTR
7.3. Genome Cyclisation and Long-Range RNA–RNA Interactions
7.4. Subgenomic Flaviviral RNA (sfRNA)
8. Future Work
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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van den Elsen, K.; Quek, J.P.; Luo, D. Molecular Insights into the Flavivirus Replication Complex. Viruses 2021, 13, 956. https://doi.org/10.3390/v13060956
van den Elsen K, Quek JP, Luo D. Molecular Insights into the Flavivirus Replication Complex. Viruses. 2021; 13(6):956. https://doi.org/10.3390/v13060956
Chicago/Turabian Stylevan den Elsen, Kaïn, Jun Ping Quek, and Dahai Luo. 2021. "Molecular Insights into the Flavivirus Replication Complex" Viruses 13, no. 6: 956. https://doi.org/10.3390/v13060956
APA Stylevan den Elsen, K., Quek, J. P., & Luo, D. (2021). Molecular Insights into the Flavivirus Replication Complex. Viruses, 13(6), 956. https://doi.org/10.3390/v13060956