Article ; Online: Akt1 is involved in HCV release by promoting endoplasmic reticulum-to-endosome transition of infectious virions.
2024 Volume 338, Page(s) 122412
Abstract: Aims: Hepatitis C virus (HCV) relies on the viral and host factors to complete its life cycle. It has evolved to profit from Akt activation at some stage in its life cycle through various mechanisms, notably by activating lipogenesis, which is crucial ... ...
| Abstract | Aims: Hepatitis C virus (HCV) relies on the viral and host factors to complete its life cycle. It has evolved to profit from Akt activation at some stage in its life cycle through various mechanisms, notably by activating lipogenesis, which is crucial for infectious virions production. Materials and methods: By employing an Akt-specific inhibitor, the impact of Akt on intracellular and extracellular infectivity was investigated. To ascertain the role of Akt in the HCV life cycle, the two-part cell culture-derived HCV infection protocol utilizing Akt1 small interfering RNAs (siRNAs) was implemented. The impact of Akt1 on intracellular HCV transition was determined using membrane flotation assay and proximity ligation assay coupled with Anti-Rab7 immunoprecipitation and immunofluorescence. Key findings: Akt1 silencing reduced infectious virions release to a degree comparable to that of ApoE, a host component involved in the HCV assembly and release, suggesting Akt1 was critical in the late stage of the HCV life cycle. Extracellular infectivity of HCV was inhibited by brefeldin A, and the inhibitory effect was augmented by Akt1 silencing and partially restored by ectopic Akt1 expression. Immunofluorescence revealed that Akt1 inhibition suppressed the interaction between HCV core protein and lipid droplet. Akt1 silencing impeded the transition of HCV from the endoplasmic reticulum to the endosome and hence inhibited the secretion of HCV infectious virions from the late endosome. Significance: Our study demonstrates that Akt1 has an impact on the lipogenesis pathway and plays a critical role in the assembly and secretion of infectious HCV. |
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| MeSH term(s) | Humans ; Endoplasmic Reticulum/metabolism ; Endosomes ; Hepacivirus/metabolism ; Hepatitis C/genetics ; Proto-Oncogene Proteins c-akt/metabolism ; RNA, Small Interfering/metabolism ; Virion ; Virus Assembly/physiology |
| Chemical Substances | Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; RNA, Small Interfering |
| Language | English |
| Publishing date | 2024-01-06 |
| Publishing country | Netherlands |
| Document type | Journal Article |
| ZDB-ID | 3378-9 |
| ISSN | 1879-0631 ; 0024-3205 |
| ISSN (online) | 1879-0631 |
| ISSN | 0024-3205 |
| DOI | 10.1016/j.lfs.2024.122412 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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