Virus Details


VHFID5341

Host Factor Information

Gene Name LARP1
HF Protein Name La-related protein 1
HF Function Essential for virus replication
Uniprot ID Q6PKG0
Protein Sequence View Fasta Sequence
NCBI Gene ID 23367
Host Factor (HF) Name in Paper LARP1
Gene synonyms KIAA0731 LARP
Ensemble Gene ID ENSG00000155506
Ensemble Transcript ENST00000336314 [Q6PKG0-3]
KEGG ID Go to KEGG Database
Gene Ontology ID(s) GO:0000339, GO:0003723, GO:0003730, GO:0005737, GO:0006413, GO:0008190, GO:0008283, GO:0008494, GO:0010494, GO:0016020, GO:0016239, GO:0017148, GO:0031369, GO:0031929, GO:0038202, GO:0045070, GO:0045296, GO:0048027, GO:0048255, GO:0072752, GO:1990928,
MINT ID Q6PKG0
STRING Click to see interaction map
GWAS Analysis Click to see gwas analysis
OMIM ID 612059
PANTHER ID N.A.
PDB ID(s) 4ZC4, 5C0V, 5V4R, 5V7C, 5V87,
pfam ID PF05383,
Drug Bank ID N.A.,
ChEMBL ID N.A.
Organism Homo sapiens (Human)

Pathogen Information

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

Publication Information

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