| Gene Name | SPCS1 |
| HF Protein Name | Signal peptidase complex subunit 1 |
| HF Function | Participates in the assembly of JEV particles |
| Uniprot ID | Q9Y6A9 |
| Protein Sequence | View Fasta Sequence |
| NCBI Gene ID | 28972 |
| Host Factor (HF) Name in Paper | SPCS1 |
| Gene synonyms | SPC12 |
| Ensemble Gene ID | ENSG00000114902 |
| Ensemble Transcript | ENST00000602728 |
| KEGG ID | Go to KEGG Database |
| Gene Ontology ID(s) | GO:0005787, GO:0005789, GO:0006465, GO:0006508, GO:0008233, GO:0030176, GO:0031090, GO:0045047, |
| MINT ID | N.A. |
| STRING | Click to see interaction map |
| GWAS Analysis | Click to see gwas analysis |
| OMIM ID | 610358 |
| PANTHER ID | PTHR13202;PTHR13202:SF0 |
| PDB ID(s) | N.A., |
| pfam ID | PF06645, |
| Drug Bank ID | N.A., |
| ChEMBL ID | N.A. |
| Organism | Homo sapiens (Human) |
| Virus Name | Japanese encephalitis virus |
| Virus Short Name | JEV |
| Order | Unassigned |
| Virus Family | Flaviviridae |
| Virus Subfamily | N.A. |
| Genus | Flavivirus |
| Species | Japanese encephalitis virus |
| Host | Human, mammals, mosquitoes and ticks |
| Cell Tropism | N.A. |
| Associated Disease | Hemorrhagic fever, encephalitis |
| Mode of Transmission | Arthropod bite, mainly mosquitoes |
| VIPR DB link | http://www.viprbrc.org/brc/home.spg?decorator=flavi |
| ICTV DB link | https://talk.ictvonline.org/ictv-reports/ictv_online_report/positive-sense-rna-viruses/w/flaviviridae |
| Virus Host DB link | http://www.genome.jp/virushostdb/view/?virus_lineage=Flaviviridae |
| Paper Title | Host factor SPCS1 regulates the replication of Japanese encephalitis virus through interactions with transmembrane domains of NS2B |
| Author's Name | Le Maa, Fang Lia, Jing-Wei Zhanga, Wei Lia, Dong-Ming Zhaoa, Han Wang Rong-Hong Huaa, Zhi-Gao Bua |
| Journal Name | Journal Of Virology |
| Pubmed ID | 29593046 |
| Abstract | Signal peptidase complex subunit 1 (SPCS1) is a newly identified host factor that regulates flavivirus replication, but the molecular mechanism is not fully understood. Herein, using Japanese encephalitis virus (JEV) as a model, we investigated the mechanism through which host factor SPCS1 regulates the replication of flaviviruses. We first validated the regulatory function of SPCS1 in JEV propagation by knocking down and knocking out endogenous SPCS1. Loss of SPCS1 function markedly reduced intracellular virion assembly and production of infectious JEV particles, but did not affect virus cell entry, RNA replication, or translation. SPCS1 was found to interact with NS2B, which is involved in post-translational protein processing and viral assembly. Serial deletion mutation of the JEV NS2B protein revealed that two transmembrane domains, NS2B (1-49) and NS2B (84-131), interact with SPCS1. Further mutagenesis analysis of conserved flavivirus residues in two SPCS1 interaction domains of NS2B demonstrated that G12A, G37A, and G47A in NS2B (1-49), and P112A in NS2B (84-131), weakened the interaction with SPCS1. Deletion mutation of SPCS1 revealed that SPCS1 (91-169) which containing two transmembrane domains was involved in the interaction with both NS2B (1-49) and NS2B (84-131). Taken together, the results demonstrate that SPCS1 affects viral replication by interacting with NS2B, thereby influencing post-translational processing of JEV proteins and the assembly of virions.IMPORTANCEUnderstanding viral-host interactions is important for elucidating the molecular mechanisms of viral propagation, and identifying potential anti-viral targets. Previous reports demonstrated that SPCS1 is involved in the flavivirus life cycle, but the mechanism remains unknown. In this study, we confirmed that SPCS1 participates in the post-translational protein processing and viral assembly stages of the JEV lifecycle, but not in the cell entry, genome RNA replication, or translation stages. Furthermore, we found that SPCS1 interacts with two independent transmembrane domains of the Flavivirus NS2B protein. NS2B also interacts with NS2A, which is proposed to mediate viral assembly. Therefore, we propose a protein-protein interaction model showing how SPCS1 participates in the assembly of JEV particles. The findings expand our understanding of how host factors participate in the flavivirus replication lifecycle, and identify potential anti-viral targets for combatting flavivirus infection. |
| Used Model | 293T cells |
| DOI | 10.1128/JVI.00197-18 |
