Nascent polyprotein starts folding in ER

Stable Identifier
R-HSA-9923067
Type
Reaction [uncertain]
Species
Homo sapiens
Related Species
Dengue virus type 2
Compartment
cytosol
ReviewStatus
5/5
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Nascent polyprotein starts folding in ER
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Host ribosomes translate the DENV genomic RNA, producing a polyprotein of 3,391 aa length and mass of about 380 kDa. Critical are the 60S-ribosomal subunits RPLP1 and RPLP2, which relieve ribosomal pausing in the sequence coding for the N-terminus of the DENV envelope protein (E), implying a role for RPLP1/2 in multi-pass transmembrane protein biogenesis (Campos et al., 2020). Cytosolic chaperones HSPA8, HSPA1, DNAJA2, and BAG2 are recruited to viral polysomes and are critical for DENV replication, supporting viral protein biogenesis (Taguwa et al., 2015; Aviner et al., 2021; reviewed in Aviner & Frydman, 2019). Another requirement is the recruitment of a NPL4(NPLOC4):VCP complex by NS4B at the replication organelle, preventing the formation of stress granules. Stress granules inhibit protein synthesis, impacting viral replication by sequestering mRNAs and translation factors (Arakawa et al., 2022; see Mazeaud et al., 2021 for the VCP requirement).

Translation initiation of the DENV genomic RNA can be cap-dependent or cap-independent. Cap-independent pathways include 5′-3′end-dependent internal ribosome entry site (IRES)-independent initiation (Edgil et al., 2006), and IRES-mediated initiation (Song et al., 2019; Fernandez-Garcia et al., 2021).
Literature References
PubMed ID Title Journal Year
26582131 Defining Hsp70 Subnetworks in Dengue Virus Replication Reveals Key Vulnerability in Flavivirus Infection

Taguwa, S, Maringer, K, Li, X, Bernal-Rubio, D, Rauch, JN, Gestwicki, JE, Andino, R, Fernandez-Sesma, A, Frydman, J

Cell 2015
34408324 Cotranslational prolyl hydroxylation is essential for flavivirus biogenesis

Aviner, R, Li, KH, Frydman, J, Andino, R

Nature 2021
16501107 Dengue virus utilizes a novel strategy for translation initiation when cap-dependent translation is inhibited

Edgil, D, Polacek, C, Harris, E

J Virol 2006
32890404 Ribosomal stalk proteins RPLP1 and RPLP2 promote biogenesis of flaviviral and cellular multi-pass transmembrane proteins

Campos, RK, Wijeratne, HRS, Shah, P, Garcia-Blanco, MA, Bradrick, SS

Nucleic Acids Res 2020
35063505 Flavivirus recruits the valosin-containing protein-NPL4 complex to induce stress granule disassembly for efficient viral genome replication

Arakawa, M, Tabata, K, Ishida, K, Kobayashi, M, Arai, A, Ishikawa, T, Suzuki, R, Takeuchi, H, Tripathi, LP, Mizuguchi, K, Morita, E

J Biol Chem 2022
30967466 Dengue and Zika Virus 5' Untranslated Regions Harbor Internal Ribosomal Entry Site Functions

Song, Y, Mugavero, J, Stauft, CB, Wimmer, E

mBio 2019
30858229 Proteostasis in Viral Infection: Unfolding the Complex Virus-Chaperone Interplay

Aviner, R, Frydman, J

Cold Spring Harb Perspect Biol 2020
33298544 The internal ribosome entry site of the Dengue virus mRNA is active when cap-dependent translation initiation is inhibited

Fernández-García, L, Angulo, J, Ramos, H, Barrera, A, Pino, K, Vera-Otarola, J, López-Lastra, M

J Virol 2021
34696522 The Biogenesis of Dengue Virus Replication Organelles Requires the ATPase Activity of Valosin-Containing Protein

Mazeaud, C, Anton, A, Pahmeier, F, Sow, AA, Cerikan, B, Freppel, W, Cortese, M, Bartenschlager, R, Chatel-Chaix, L

Viruses 2021
Participants
Input
Output
Participates
as an event of
Event Information
Go Biological Process
viral translation (0019081)
This event is regulated
Requirements
Disease
Name Identifier Synonyms
dengue disease DOID:12205 breakbone fever, Dengue Fever, classic dengue
Cross References
Mondo
Authored
Stephan, R  (2024-09-28)
Reviewed
Mansur, DS  (2025-09-18)
Roque Ascenção, F  (2025-10-29)
Created
Stephan, R  (2024-09-29)
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