Article ; Online: Functionality of IAV packaging signals depends on site-specific charges within the viral nucleoprotein.
2024 Volume 98, Issue 4, Page(s) e0197223
Abstract: The coordinated packaging of the segmented genome of the influenza A virus (IAV) into virions is an essential step of the viral life cycle. This process is controlled by the interaction of packaging signals present in all eight viral RNA (vRNA) segments ... ...
| Abstract | The coordinated packaging of the segmented genome of the influenza A virus (IAV) into virions is an essential step of the viral life cycle. This process is controlled by the interaction of packaging signals present in all eight viral RNA (vRNA) segments and the viral nucleoprotein (NP), which binds vRNA via a positively charged binding groove. However, mechanistic models of how the packaging signals and NP work together to coordinate genome packaging are missing. Here, we studied genome packaging in influenza A/SC35M virus mutants that carry mutated packaging signals as well as specific amino acid substitutions at the highly conserved lysine (K) residues 184 and 229 in the RNA-binding groove of NP. Because these lysines are acetylated and thus neutrally charged in infected host cells, we replaced them with glutamine to mimic the acetylated, neutrally charged state or arginine to mimic the non-acetylated, positively charged state. Our analysis shows that the coordinated packaging of eight vRNAs is influenced by (i) the charge state of the replacing amino acid and (ii) its location within the RNA-binding groove. Accordingly, we propose that lysine acetylation induces different charge states within the RNA-binding groove of NP, thereby supporting the activity of specific packaging signals during coordinated genome packaging. Importance: Influenza A viruses (IAVs) have a segmented viral RNA (vRNA) genome encapsidated by multiple copies of the viral nucleoprotein (NP) and organized into eight distinct viral ribonucleoprotein complexes. Although genome segmentation contributes significantly to viral evolution and adaptation, it requires a highly sophisticated genome-packaging mechanism. How eight distinct genome complexes are incorporated into the virion is poorly understood, but previous research suggests an essential role for both vRNA packaging signals and highly conserved NP amino acids. By demonstrating that the packaging process is controlled by charge-dependent interactions of highly conserved lysine residues in NP and vRNA packaging signals, our study provides new insights into the sophisticated packaging mechanism of IAVs. |
|||||
|---|---|---|---|---|---|---|
| MeSH term(s) | Influenza A virus/genetics ; Influenza A virus/metabolism ; Nucleoproteins/genetics ; Nucleoproteins/metabolism ; Lysine/genetics ; Virus Assembly/genetics ; Genome, Viral ; Amino Acids/genetics ; Nucleocapsid Proteins/genetics ; RNA, Viral/metabolism | |||||
| Chemical Substances | Nucleoproteins ; Lysine (K3Z4F929H6) ; Amino Acids ; Nucleocapsid Proteins ; RNA, Viral | |||||
| Language | English | |||||
| Publishing date | 2024-03-12 | |||||
| Publishing country | United States | |||||
| Document type | Journal Article | |||||
| ZDB-ID | 80174-4 | |||||
| ISSN | 1098-5514 ; 0022-538X | |||||
| ISSN (online) | 1098-5514 | |||||
| ISSN | 0022-538X | |||||
| DOI | 10.1128/jvi.01972-23 | |||||
| Shelf mark |
|
|||||
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
More links
Kategorien
In stock of ZB MED Cologne/Königswinter
| Zs.A 609: Show issues | Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG) |
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.