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PMID:26874015
| Citation |
Eyre, NS, Hampton-Smith, RJ, Aloia, AL, Eddes, JS, Simpson, KJ, Hoffmann, P and Beard, MR (2016) Phosphorylation of NS5A Serine-235 is essential to hepatitis C virus RNA replication and normal replication compartment formation. Virology 491:27-44 |
|---|---|
| Abstract |
Hepatitis C virus (HCV) NS5A protein is essential for HCV RNA replication and virus assembly. Here we report the identification of NS5A phosphorylation sites Ser-222, Ser-235 and Thr-348 during an infectious HCV replication cycle and demonstrate that Ser-235 phosphorylation is essential for HCV RNA replication. Confocal microscopy revealed that both phosphoablatant (S235A) and phosphomimetic (S235D) mutants redistribute NS5A to large juxta-nuclear foci that display altered colocalization with known replication complex components. Using electron microscopy (EM) we found that S235D alters virus-induced membrane rearrangements while EM using 'APEX2'-tagged viruses demonstrated S235D-mediated enrichment of NS5A in irregular membranous foci. Finally, using a customized siRNA screen of candidate NS5A kinases and subsequent analysis using a phospho-specific antibody, we show that phosphatidylinositol-4 kinase III alpha (PI4KIIIα) is important for Ser-235 phosphorylation. We conclude that Ser-235 phosphorylation of NS5A is essential for HCV RNA replication and normal replication complex formation and is regulated by PI4KIIIα. |
| Links |
PubMed Online version:10.1016/j.virol.2016.01.018 |
| Keywords |
Amino Acid Motifs; Amino Acid Sequence; Cell Line; Hepacivirus/chemistry; Hepacivirus/genetics; Hepacivirus/metabolism; Hepatitis C/virology; Humans; Molecular Sequence Data; Phosphorylation; RNA, Viral/chemistry; RNA, Viral/genetics; RNA, Viral/metabolism; Serine/genetics; Serine/metabolism; Viral Nonstructural Proteins/chemistry; Viral Nonstructural Proteins/genetics; Viral Nonstructural Proteins/metabolism; Virus Replication |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
|
part_of |
GO:0039714: cytoplasmic viral factory |
ECO:0000314: direct assay evidence used in manual assertion |
C |
Seeded From UniProt |
complete | |||
Notes
See also
References
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