Virus Details


VHFID9151

Host Factor Information

Gene Name TIMD4
HF Protein Name T-cell immunoglobulin and mucin domain-containing protein 4
HF Function Required for virus entry
Uniprot ID Q96H15
Protein Sequence View Fasta Sequence
NCBI Gene ID 91937
Host Factor (HF) Name in Paper TIM4
Gene synonyms TIM4
Ensemble Gene ID ENSG00000145850
Ensemble Transcript ENST00000274532 [Q96H15-1];ENST00000407087 [Q96H15-2]
KEGG ID Go to KEGG Database
Gene Ontology ID(s) GO:0016021,
MINT ID N.A.
STRING Click to see interaction map
GWAS Analysis Click to see gwas analysis
OMIM ID 610096
PANTHER ID N.A.
PDB ID(s) 5DZN, 5F7F, 5F7H,
pfam ID PF07686,
Drug Bank ID N.A.,
ChEMBL ID N.A.
Organism Homo sapiens (Human)

Pathogen Information

Virus Name Zaire ebolavirus
Virus Short Name ZEBOV
Order Bunyavirales
Virus Family Filoviridae
Virus Subfamily N.A.
Genus Ebolavirus
Species Zaire ebolavirus
Host Bats, human and primates
Cell Tropism N.A.
Associated Disease Hemorragic fever
Mode of Transmission Zoonosis, contact with body fluids
VIPR DB link http://www.viprbrc.org/brc/vipr_allSpecies_search.do?method=SubmitForm&decorator=filo
ICTV DB link https://talk.ictvonline.org/ictv-reports/ictv_9th_report/negative-sense-rna-viruses-2011/w/negrna_viruses/197/filoviridae
Virus Host DB link N.A.

Publication Information

Paper Title Characterization of human and murine T-Cell immunoglobulin mucin domain 4 (TIM-4) IgV domain residues critical for Ebola virus entry
Author's Name Bethany A. Rhein, Rachel B. Brouillette, Grace A. Schaack, John A. Chiorini, Wendy Maury
Journal Name Journal Of Virology
Pubmed ID 27122575
Abstract Phosphatidylserine (PtdSer) receptors that are responsible for the clearance of dying cells have recently been found to mediate enveloped virus entry. Ebola virus (EBOV), a member of the Filoviridae family of viruses, utilizes PtdSer receptors for entry into target cells. The PtdSer receptors human and murine T-cell immunoglobulin mucin (TIM) domain proteins TIM-1 and TIM-4 mediate filovirus entry by binding to PtdSer on the virion surface via a conserved PtdSer binding pocket within the amino-terminal IgV domain. While the residues within the TIM-1 IgV domain that are important for EBOV entry are characterized, the molecular details of virion-TIM-4 interactions have yet to be investigated. As sequences and structural alignments of the TIM proteins suggest distinct differences in the TIM-1 and TIM-4 IgV domain structures, we sought to characterize TIM-4 IgV domain residues required for EBOV entry. Using vesicular stomatitis virus pseudovirions bearing EBOV glycoprotein (EBOV GP/VSVΔG), we evaluated virus binding and entry into cells expressing TIM-4 molecules mutated within the IgV domain, allowing us to identify residues important for entry. Similar to TIM-1, residues in the PtdSer binding pocket of murine and human TIM-4 (mTIM-4 and hTIM-4) were found to be important for EBOV entry. However, additional TIM-4-specific residues were also found to impact EBOV entry, with a total of 8 mTIM-4 and 14 hTIM-4 IgV domain residues being critical for virion binding and internalization. Together, these findings provide a greater understanding of the interaction of TIM-4 with EBOV virions.
Used Model HEK 293T and HEK 293 cells
DOI 10.1128/JVI.00100-16