Attachment Protein G of an African Bat Henipavirus Is Differentially Restricted in Chiropteran and Nonchiropteran Cells

Krüger, Nadine; Hoffmann, Markus; Drexler, Jan Felix; Müller, Marcel A.; Corman, Victor M.; Drosten, Christian; Herrler, Georg

doi:10.1128/jvi.01561-14

Cited by 11 publications

(16 citation statements)

References 34 publications

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“…In contrast, syncytium formation induced by the glycoproteins of the African henipavirus is restricted to chiropteran cells and not observed in cells of other mammalian species (33,46,47). This differential fusion activity has been traced back to the surface transport of the G protein, which was inefficient in all cells, but the inefficiency was less pronounced in chiropteran cells (28). The fusion activity of the batMuV glycoproteins differs from that of the African henipavirus, as it is not restricted to chiropteran cells.…”

Section: Discussionmentioning

confidence: 88%

“…BHK-21, Vero76, and HeLa cells (kindly provided by A. Maisner) were maintained in Dulbecco's minimum essential medium (DMEM; Gibco) supplemented with 5% fetal calf serum (FCS; Biochrom). Chiropteran cells derived from different species and organs were used in this study: HypNi/1.1 (Hypsignathus monstrosus kidney cells), a clonal cell line produced from a mixed culture (HypNi/1) (27), HypLu/2 (Hypsignathus monstrosus lung cells, mixed culture) (28), and EidNi/41 cells (Eidolon helvum kidney cells, mixed culture) (29) were maintained in DMEM containing 10% FCS. All cells were cultivated in 75-cm 2 tissue culture flasks (Greiner Bio-One) at 37°C and 5% CO 2 .…”

Section: Sequence Homology Analysismentioning

confidence: 99%

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Functional Properties and Genetic Relatedness of the Fusion and Hemagglutinin-Neuraminidase Proteins of a Mumps Virus-Like Bat Virus

Krüger

Hoffmann

Drexler

et al. 2015

J Virol

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A bat virus with high phylogenetic relatedness to human mumps virus (MuV) was identified recently at the nucleic acid level. We analyzed the functional activities of the hemagglutinin-neuraminidase (HN) and the fusion (F) proteins of the bat virus (batMuV) and compared them to the respective proteins of a human isolate. Transfected cells expressing the F and HN proteins of batMuV were recognized by antibodies directed against these proteins of human MuV, indicating that both viruses are serologically related. Fusion, hemadsorption, and neuraminidase activities were demonstrated for batMuV, and either bat-derived protein could substitute for its human MuV counterpart in inducing syncytium formation when coexpressed in different mammalian cell lines, including chiropteran cells. Cells expressing batMuV glycoproteins were shown to have lower neuraminidase activity. The syncytia were smaller, and they were present in lower numbers than those observed after coexpression of the corresponding glycoproteins of a clinical isolate of MuV (hMuV). The phenotypic differences in the neuraminidase and fusion activity between the glycoproteins of batMuV and hMuV are explained by differences in the expression level of the HN and F proteins of the two viruses. In the case of the F protein, analysis of chimeric proteins revealed that the signal peptide of the bat MuV fusion protein is responsible for the lower surface expression. These results indicate that the surface glycoproteins of batMuV are serologically and functionally related to those of hMuV, raising the possibility of bats as a reservoir for interspecies transmission. IMPORTANCEThe recently described MuV-like bat virus is unique among other recently identified human-like bat-associated viruses because of its high sequence homology (approximately 90% in most genes) to its human counterpart. Although it is not known if humans can be infected by batMuV, the antigenic relatedness between the bat and human forms of the virus suggests that humans carrying neutralizing antibodies against MuV are protected from infection by batMuV. The close functional relationship between MuV and batMuV is demonstrated by cooperation of the respective HN and F proteins to induce syncytium formation in heterologous expression studies. An interesting feature of the glycoproteins of batMuV is the downregulation of the fusion activity by the signal peptide of F, which has not been reported for other paramyxoviruses. These results are important contributions for risk assessment and for a better understanding of the replication strategy of batMuV.

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Section: Discussionmentioning

confidence: 88%

Section: Sequence Homology Analysismentioning

confidence: 99%

Functional Properties and Genetic Relatedness of the Fusion and Hemagglutinin-Neuraminidase Proteins of a Mumps Virus-Like Bat Virus

Krüger

Hoffmann

Drexler

et al. 2015

J Virol

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“…All non-bat-derived cell lines were obtained from collaborators. The fruit bat cell lines were kindly provided by C. Drosten and M. A. Müller and have been described previously (27)(28)(29)(30)(31). All cell lines were grown in a humidified atmosphere at 37°C and 5% CO 2 .…”

Section: Methodsmentioning

confidence: 99%

A Polymorphism within the Internal Fusion Loop of the Ebola Virus Glycoprotein Modulates Host Cell Entry

Hoffmann

Crone

Dietzel

et al. 2017

J Virol

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The large scale of the Ebola virus disease (EVD) outbreak in West Africa in 2013-2016 raised the question whether the host cell interactions of the responsible Ebola virus (EBOV) strain differed from those of other ebolaviruses. We previously reported that the glycoprotein (GP) of the virus circulating in West Africa in 2014 (EBOV2014) exhibited reduced ability to mediate entry into two nonhuman primate (NHP)-derived cell lines relative to the GP of EBOV1976. Here, we investigated the molecular determinants underlying the differential entry efficiency. We found that EBOV2014-GP-driven entry into diverse NHP-derived cell lines, as well as human monocyte-derived macrophages and dendritic cells, was reduced compared to EBOV1976-GP, although entry into most human-and all bat-derived cell lines tested was comparable. Moreover, EBOV2014 replication in NHP but not human cells was diminished relative to EBOV1976, suggesting that reduced cell entry translated into reduced viral spread. Mutagenic analysis of EBOV2014-GP and EBOV1976-GP revealed that an amino acid polymorphism in the receptor-binding domain, A82V, modulated entry efficiency in a cell line-independent manner and did not account for the reduced EBOV2014-GP-driven entry into NHP cells. In contrast, polymorphism T544I, located in the internal fusion loop in the GP2 subunit, was found to be responsible for the entry phenotype. These results suggest that position 544 is an important determinant of EBOV infectivity for both NHP and certain human target cells. IMPORTANCEThe Ebola virus disease outbreak in West Africa in 2013 entailed more than 10,000 deaths. The scale of the outbreak and its dramatic impact on human health raised the question whether the responsible virus was particularly adept at infecting human cells. Our study shows that an amino acid exchange, A82V, that was acquired during the epidemic and that was not observed in previously circulating viruses, increases viral entry into diverse target cells. In contrast, the epidemic virus showed a reduced ability to enter cells of nonhuman primates compared to the virus circulating in 1976, and a single amino acid exchange in the internal fusion loop of the viral glycoprotein was found to account for this phenotype.

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“…Bat cell lines from the following species were maintained in DMEM supplemented with 10% FCS: Eidolon helvum (kidney, EidNi/41; lung, EidLu/43), Epomops buettikoferi (kidney, EpoNi/22.1), Hypsignathus monstrosus (kidney, HypNi/1.1; lung, HypLu/2), Rousettus aegyptiacus (kidney, RoNi/7) and Pipistrellus spec. (kidney, PipNi/3) (Biesold et al, 2011;Hoffmann et al, 2013;Kr€ uger et al, 2014). HEK293T (Homo sapiens, kidney), BHK-21 (Mesocricetus auratus, kidney) and Vero76 cells (Cercopithecus aethiops, kidney) were maintained in DMEM supplemented with 5% FCS.…”

Section: Declaration Of Interestsmentioning

confidence: 99%

Entry, Replication, Immune Evasion, and Neurotoxicity of Synthetically Engineered Bat-Borne Mumps Virus

et al. 2018

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Attachment Protein G of an African Bat Henipavirus Is Differentially Restricted in Chiropteran and Nonchiropteran Cells

Cited by 11 publications

References 34 publications

Functional Properties and Genetic Relatedness of the Fusion and Hemagglutinin-Neuraminidase Proteins of a Mumps Virus-Like Bat Virus

Functional Properties and Genetic Relatedness of the Fusion and Hemagglutinin-Neuraminidase Proteins of a Mumps Virus-Like Bat Virus

A Polymorphism within the Internal Fusion Loop of the Ebola Virus Glycoprotein Modulates Host Cell Entry

Entry, Replication, Immune Evasion, and Neurotoxicity of Synthetically Engineered Bat-Borne Mumps Virus

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