Niemann-Pick C1 Heterogeneity of Bat Cells Controls Filovirus Tropism

Takadate, Yoshihiro; Kondoh, Tatsunari; Igarashi, Manabu; Maruyama, Junki; Manzoor, Rashid; Ogawa, Hirohito; Kajihara, Masahiro; Furuyama, Wakako; Miyamoto, Hiroko; Yoshida, Reiko; Hill, Terence E.; Freiberg, Alexander N.; Feldmann, Heinz; Marzi, Andrea; Takada, Ayato

doi:10.1016/j.celrep.2019.12.042

Cited by 24 publications

(44 citation statements)

References 73 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…SuBK12-08 cells were identified by morphology, habitat, and BLAST searches using the sequences of the cytochrome b gene [ 27 ]. Vero E6/NPC1-KO cl.19 and Vero E6/NPC1-KO cl.19, expressing exogenous NPC1 derived from HEK293T or SuBK12-08, were generated and maintained as described previously [ 20 , 28 ].…”

Section: Methodsmentioning

confidence: 99%

“…We used the nucleotide sequences of NPC1 genes derived from SuBK12-08, YubFKT1, BKT1, FBKT1, ZFBK13-76E, ZFBK11-97, ZFBK15-137RA, and DemKT1, which were determined previously (GenBank accession numbers; LC462997, LC462271, LC462998, LC462999, LC462993, LC462994, LC462995, and LC462996, respectively [ 20 ]). Total RNA was extracted from SuBK12-08 cells using ISOGEN (Nippongene) and mRNA was reverse transcribed with Superscript IV (Invitrogen).…”

Section: Methodsmentioning

confidence: 99%

“…Vero E6/NPC1-KO cl.19 cells expressing human NPC1, HEK293T/SuBK12-08 NPC1, and their mutants were generated as described previously [ 20 ]. Briefly, HEK293T-derived Platinum-GP cells (Cell Biolabs) were cotransfected with pMXs-puro encoding NPC1 genes and the expression of plasmid pCAGGS encoding the VSV G using Lipofectamine 2000 (Invitrogen, Carlsbad, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

“…One of the important steps is the entry of viruses into cells, which is generally mediated by interactions between viral surface proteins and host cell receptors [ 17 ]. Previous studies have suggested that each filovirus has a different preference for bat species [ 18 , 19 , 20 ], which may be principally determined by the interactions between GPs and filovirus receptors. Previously, we compared the susceptibilities of bat-derived cell lines to filoviruses, using vesicular stomatitis viruses (VSVs) pseudotyped with GPs, and found that filoviruses might have preferential tropism to some particular bat species depending on the virus species.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Receptor-Mediated Host Cell Preference of a Bat-Derived Filovirus, Lloviu Virus

et al. 2020

Self Cite

View full text Add to dashboard Cite

Lloviu virus (LLOV), a bat-derived filovirus that is phylogenetically distinct from human pathogenic filoviruses such as Ebola virus (EBOV) and Marburg virus (MARV), was discovered in Europe. However, since infectious LLOV has never been isolated, the biological properties of this virus remain poorly understood. We found that vesicular stomatitis virus (VSV) pseudotyped with the glycoprotein (GP) of LLOV (VSV–LLOV) showed higher infectivity in one bat (Miniopterus sp.)-derived cell line than in the other bat-derived cell lines tested, which was distinct from the tropism of VSV pseudotyped with EBOV (VSV–EBOV) and MARV GPs. We then focused on the interaction between GP and Niemann–Pick C1 (NPC1) protein, one of the cellular receptors of filoviruses. We introduced the Miniopterus bat and human NPC1 genes into NPC1-knockout Vero E6 cells and their susceptibilities to the viruses were compared. The cell line expressing the bat NPC1 showed higher susceptibility to VSV–LLOV than that expressing human NPC1, whereas the opposite preference was seen for VSV–EBOV. Using a site-directed mutagenesis approach, amino acid residues involved in the differential tropism were identified in the NPC1 and GP molecules. Our results suggest that the interaction between GP and NPC1 is an important factor in the tropism of LLOV to a particular bat species.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Receptor-Mediated Host Cell Preference of a Bat-Derived Filovirus, Lloviu Virus

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…Recent research advances are beginning to shed light on the molecular mechanisms by which bats avoid pathology from these otherwise virulent pathogens (Brook and Dobson, 2015). Bats leverage a suite of species-specific mechanisms to limit viral load, which include host receptor sequence incompatibilities for some bat-virus combinations (Ng et al, 2015;Takadate et al, 2020) and constitutive expression of the antiviral cytokine, IFN-a, for others (Zhou et al, 2016). Typically, the presence of viral RNA or DNA in the cytoplasm of mammalian cells will induce secretion of type I interferon proteins (IFN-a and IFN-b), which promote expression and translation of interferon-stimulated genes (ISGs) in neighboring cells and render them effectively antiviral (Stetson and Medzhitov, 2006).…”

Section: Introductionmentioning

confidence: 99%

Accelerated viral dynamics in bat cell lines, with implications for zoonotic emergence

Brook

Boots

Chandran

et al. 2020

eLife

101

View full text Add to dashboard Cite

Bats host virulent zoonotic viruses without experiencing disease. A mechanistic understanding of the impact of bats' virus hosting capacities, including uniquely constitutive immune pathways, on cellular-scale viral dynamics is needed to elucidate zoonotic emergence. We carried out virus infectivity assays on bat cell lines expressing induced and constitutive immune phenotypes, then developed a theoretical model of our in vitro system, which we fit to empirical data. Best fit models recapitulated expected immune phenotypes for representative cell lines, supporting robust antiviral defenses in bat cells that correlated with higher estimates for withinhost viral propagation rates. In general, heightened immune responses limit pathogen-induced cellular morbidity, which can facilitate the establishment of rapidly-propagating persistent infections within-host. Rapidly-transmitting viruses that have evolved with bat immune systems will likely cause enhanced virulence following emergence into secondary hosts with immune systems that diverge from those unique to bats.Brook et al. eLife 2020;9:e48401.

show abstract

Distinct interferon response in bat and other mammalian cell lines infected with Pteropine orthoreovirus

et al. 2021

View full text Add to dashboard Cite

Bats serve as natural hosts of Pteropine orthoreovirus (PRV), an emerging group of bat-borne, zoonotic viruses. Bats appear to possess unique innate immune system responses that can inhibit viral replication, thus reducing clinical symptoms. We examined the innate immune response against PRV and assessed viral replication in cell lines derived from four bat species ( Miniopterus fuliginosus , Pteropus dasymallus , Rhinolophus ferrumequinum , and Rousettus leschenaultii ), one rodent ( Mesocricetous auratus ), and human ( Homo sapiens ). The expression levels of pattern recognition receptors (PRRs) ( TLR3 , RIG-I , and MDA5 ) and interferons ( IFNB1 and IFNL1 ) were higher and PRV replication was lower in cell lines derived from M. fuliginosus , R. ferrumequinum , and R. leschenaultii . Reduction of IFNB1 expression by the knockdown of PRRs in the cell line derived from R. ferrumequinum was associated with increased PRV replication. The knockdown of RIG-I led to the most significant reduction in viral replication for all cell lines. These results suggest that RIG-I production is important for antiviral response against PRV in R. ferrumequinum . Supplementary Information The online version contains supplementary material available at 10.1007/s11262-021-01865-6.

show abstract

Niemann-Pick C1 Heterogeneity of Bat Cells Controls Filovirus Tropism

Cited by 24 publications

References 73 publications

Receptor-Mediated Host Cell Preference of a Bat-Derived Filovirus, Lloviu Virus

Receptor-Mediated Host Cell Preference of a Bat-Derived Filovirus, Lloviu Virus

Accelerated viral dynamics in bat cell lines, with implications for zoonotic emergence

Distinct interferon response in bat and other mammalian cell lines infected with Pteropine orthoreovirus

Contact Info

Product

Resources

About