OmniVira

Literature detail

Niemann-Pick C1 Heterogeneity of Bat Cells Controls Filovirus Tropism.

Yoshihiro Takadate1 Tatsunari Kondoh1 Manabu Igarashi2,3 Junki Maruyama1 Rashid Manzoor1 Hirohito Ogawa4,5 Masahiro Kajihara1 Wakako Furuyama6 Masahiro Sato1 Hiroko Miyamoto1 Reiko Yoshida1 Terence E Hill7 Alexander N Freiberg7 Heinz Feldmann6 Andrea Marzi6 Ayato Takada2,8,9
Affiliations 9 institutions
  1. Division of Global Epidemiology, Research Center for Zoonosis Control, Hokkaido University, Sapporo 001-0020, Japan.
  2. Division of Global Epidemiology, Research Center for Zoonosis Control, Hokkaido University, Sapporo 001-0020, Japan
  3. Global Station for Zoonosis Control, Global Institution for Collaborative Research and Education, Hokkaido University, Sapporo 001-0020, Japan.
  4. Hokudai Center for Zoonosis Control in Zambia, School of Veterinary Medicine, University of Zambia, Lusaka 10101, Zambia
  5. Department of Disease Control, School of Veterinary Medicine, University of Zambia, Lusaka 10101, Zambia.
  6. Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, MT 59840, USA.
  7. Department of Pathology, The University of Texas Medical Branch, Galveston, TX 77555, USA.
  8. Global Station for Zoonosis Control, Global Institution for Collaborative Research and Education, Hokkaido University, Sapporo 001-0020, Japan
  9. Department of Disease Control, School of Veterinary Medicine, University of Zambia, Lusaka 10101, Zambia. Electronic address: [email protected].
PMID 31940478 2020 Cell Rep eng ppublish
PubMed DOI Browse context

Article

Publication summary

Fruit bats are suspected to be natural hosts of filoviruses, including Ebola virus (EBOV) and Marburg virus (MARV). Interestingly, however, previous studies suggest that these viruses have different tropisms depending on the bat species. Here, we show a molecular basis underlying the host-range restriction of filoviruses. We find that bat-derived cell lines FBKT1 and ZFBK13-76E show preferential susceptibility to EBOV and MARV, respectively, whereas the other bat cell lines tested are similarly infected with both viruses. In FBKT1 and ZFBK13-76E, unique amino acid (aa) sequences are found in the Niemann-Pick C1 (NPC1) protein, one of the cellular receptors interacting with the filovirus glycoprotein (GP). These aa residues, as well as a few aa differences between EBOV and MARV GPs, are crucial for the differential susceptibility to filoviruses. Taken together, our findings indicate that the heterogeneity of bat NPC1 orthologs is an important factor controlling filovirus species-specific host tropism.

bat Ebola virus filovirus glycoprotein host range Marburg virus natural host Niemann-Pick C1 receptor virus-host interaction Amino Acid Sequence Animals Chiroptera Filoviridae Humans Models, Molecular Niemann-Pick C1 Protein Tropism

Structured evidence records

Evidence records

6 total
Host Range Experiment 2 records
Host Range Experiment Extraction confidence 0.92
Key finding

The bat-derived FBKT1 cell line is preferentially susceptible to Ebola virus infection, indicating host-cell-dependent tropism linked to NPC1 receptor variation.

Virus
EBOV
Location
Not specified
Supporting text

Bat-derived cell lines FBKT1 and ZFBK13-76E show preferential susceptibility to Ebola virus and Marburg virus, respectively, whereas the other bat cell lines tested are similarly infected with both viruses.

Method
experimental infection; cell-entry assay
Experimental system
in vitro cell culture
Host Range Experiment Extraction confidence 0.92
Key finding

The bat-derived ZFBK13-76E cell line is preferentially susceptible to Marburg virus infection, demonstrating species-specific tropism controlled by NPC1 variants.

Virus
MARV
Location
Not specified
Supporting text

Bat-derived cell lines FBKT1 and ZFBK13-76E show preferential susceptibility to Ebola virus and Marburg virus, respectively, whereas the other bat cell lines tested are similarly infected with both viruses.

Method
experimental infection; cell-entry assay
Experimental system
in vitro cell culture
Molecular Adaptation 2 records
Molecular Adaptation Extraction confidence 0.95
Key finding

Amino acid variations in bat NPC1 receptor and in Ebola and Marburg virus glycoproteins determine bat species-specific infection susceptibility, showing receptor-mediated molecular adaptation.

Virus
EBOV
Host
Not specified
Location
Not specified
Supporting text

Unique amino acid sequences are found in the Niemann-Pick C1 (NPC1) protein of certain bat cell lines, and a few amino acid differences between EBOV and MARV glycoproteins are crucial for the differential susceptibility to filoviruses, indicating that heterogeneity of bat NPC1 orthologs controls filovirus tropism.

Genes or proteins
Niemann-Pick C1; glycoprotein
Receptors
Niemann-Pick C1
Host factors
Niemann-Pick C1
Mechanism types
receptor_binding; cell_entry; tropism
Molecular Adaptation Extraction confidence 0.95
Key finding

Differences in bat NPC1 receptor and Marburg virus glycoprotein amino acid sequences underlie bat cell susceptibility, evidencing receptor-mediated molecular adaptation of Marburg virus to specific bat hosts.

Virus
MARV
Host
Not specified
Location
Not specified
Supporting text

Unique amino acid sequences are found in the Niemann-Pick C1 (NPC1) protein of certain bat cell lines, and a few amino acid differences between EBOV and MARV glycoproteins are crucial for the differential susceptibility to filoviruses, indicating that heterogeneity of bat NPC1 orthologs controls filovirus tropism.

Genes or proteins
Niemann-Pick C1; glycoprotein
Receptors
Niemann-Pick C1
Host factors
Niemann-Pick C1
Mechanism types
receptor_binding; cell_entry; tropism
Receptor Usage 2 records
Receptor Usage Extraction confidence 0.98
Key finding

Filovirus tropism among bat cell lines is controlled by species-specific amino acid variations in the NPC1 receptor that mediate differential binding to Ebola and Marburg virus glycoproteins.

Virus
EBOV
Location
Not specified
Supporting text

Unique amino acid sequences are found in the Niemann-Pick C1 (NPC1) protein, one of the cellular receptors interacting with the filovirus glycoprotein (GP). These residues, as well as differences between EBOV and MARV GPs, are crucial for differential susceptibility to filoviruses.

Method
molecular analysis; infection assay
Receptors
Niemann-Pick C1 (NPC1)
Host factors
glycoprotein
Receptor Usage Extraction confidence 0.98
Key finding

Species-specific variation in the bat NPC1 receptor determines susceptibility to Marburg virus through receptor-mediated interactions with the viral glycoprotein.

Virus
MARV
Location
Not specified
Supporting text

Unique amino acid sequences are found in the Niemann-Pick C1 (NPC1) protein, one of the cellular receptors interacting with the filovirus glycoprotein (GP). These residues, as well as differences between EBOV and MARV GPs, are crucial for differential susceptibility to filoviruses.

Method
molecular analysis; infection assay
Receptors
Niemann-Pick C1 (NPC1)
Host factors
glycoprotein