Gene Name | LHX3 |
HF Protein Name | LIM/homeobox protein Lhx3 |
HF Function | Essential for virus replication |
Uniprot ID | Q9UBR4 |
Protein Sequence | View Fasta Sequence |
NCBI Gene ID | 8022 |
Host Factor (HF) Name in Paper | LHX3 |
Gene synonyms | N.A. |
Ensemble Gene ID | ENSG00000107187 |
Ensemble Transcript | ENST00000371746 [Q9UBR4-2];ENST00000371748 [Q9UBR4-1] |
KEGG ID | Go to KEGG Database |
Gene Ontology ID(s) | GO:0000978, GO:0000981, GO:0001076, GO:0001077, GO:0001085, GO:0001228, GO:0001890, GO:0005634, GO:0005667, GO:0008045, GO:0009887, GO:0021520, GO:0021521, GO:0021526, GO:0021527, GO:0021983, GO:0030324, GO:0043066, GO:0043565, GO:0045893, GO:0045944, GO:0046872, GO:0048839, |
MINT ID | N.A. |
STRING | Click to see interaction map |
GWAS Analysis | Click to see gwas analysis |
OMIM ID | 221750 |
PANTHER ID | N.A. |
PDB ID(s) | N.A., |
pfam ID | PF00046, PF00412, |
Drug Bank ID | N.A., |
ChEMBL ID | N.A. |
Organism | Homo sapiens (Human) |
Virus Name | Avian flu viruses |
Virus Short Name | H5N1 |
Order | Unassigned |
Virus Family | Orthomyxoviridae |
Virus Subfamily | N.A. |
Genus | Influenzavirus A |
Species | Influenza A virus |
Host | Aquatic birds, human, pig, horse, seals |
Cell Tropism | Epithelial respiratory cells |
Associated Disease | Acute febrile respiratory tract infection |
Mode of Transmission | Respiratory and by animal contact (in human), fecal-oral route from contaminated water (in birds ) |
VIPR DB link | http://www.genome.jp/virushostdb/view/?virus_lineage=Orthomyxoviridae |
ICTV DB link | https://talk.ictvonline.org/ictv-reports/ictv_9th_report/negative-sense-rna-viruses-2011/w/negrna_viruses/209/orthomyxoviridae |
Virus Host DB link | http://www.genome.jp/virushostdb/view/?virus_lineage=Orthomyxoviridae |
Paper Title | Genome-wide RNAi screen identifies human host factors crucial for influenza virus replication |
Author's Name | Alexander Karlas, Nikolaus Machuy, Yujin Shin, Klaus-Peter Pleissner, Anita Artarini, Dagmar Heuer, Daniel Becker, Hany Khalil, Lesley A. Ogilvie, Simone Hess, Andre P. Maurer, Elke Muller, Thorsten Wolff, Thomas Rudel & Thomas F. Meyer |
Journal Name | Nature |
Pubmed ID | 20081832 |
Abstract | Influenza A virus, being responsible for seasonal epidemics and reoccurring pandemics, represents a worldwide threat to public health. High mutation rates facilitate the generation of viral escape mutants, rendering vaccines and drugs directed against virus-encoded targets potentially ineffective. In contrast, targeting host cell determinants temporarily dispensable for the host but crucial for virus replication could prevent viral escape. Here we report the discovery of 287 human host cell genes influencing influenza A virus replication in a genome-wide RNA interference (RNAi) screen. Using an independent assay we confirmed 168 hits (59%) inhibiting either the endemic H1N1 (119 hits) or the current pandemic swine-origin (121 hits) influenza A virus strains, with an overlap of 60%. Notably, a subset of these common hits was also essential for replication of a highly pathogenic avian H5N1 strain. In-depth analyses of several factors provided insights into their infection stage relevance. Notably, SON DNA binding protein (SON) was found to be important for normal trafficking of influenza virions to late endosomes early in infection. We also show that a small molecule inhibitor of CDC-like kinase 1 (CLK1) reduces influenza virus replication by more than two orders of magnitude, an effect connected with impaired splicing of the viral M2 messenger RNA. Furthermore, influenza-virus-infected p27(-/-) (cyclin-dependent kinase inhibitor 1B Cdkn1b) mice accumulated significantly lower viral titres in the lung, providing in vivo evidence for the importance of this gene. Thus, our results highlight the potency of genome-wide RNAi screening for the dissection of virus-host interactions and the identification of drug targets for a broad range of influenza viruses. |
Used Model | A549 cells |
DOI | 10.1038/nature08760 |