Molecular Chaperone BiP Interacts with Borna Disease Virus Glycoprotein at the Cell Surface

Honda, Takeshi; Horie, Masayuki; Daito, Takuji; Ikuta, Kazuyoshi; Tomonaga, Keizō

doi:10.1128/jvi.01201-09

Cited by 61 publications

(49 citation statements)

References 35 publications

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“…GRP78 is known to be an ER-resident chaperone protein but has also been reported to be present on the plasma membranes of several cell types, including neurons (22)(23)(24)(25)(26)(27)30). For GRP78 to be involved in JEV entry, it must be located on the cell membrane.…”

Section: Resultsmentioning

confidence: 99%

“…GRP78 levels on the plasma membrane are generally considered to be low under normal physiological conditions, with increased levels seen in cancer cells and under conditions of cellular stress. However, several studies have shown that GRP78 is copiously localized under normal conditions on the plasma membrane in different cell types, including endothelial cells, monocytes, and neurons, carrying out varied functions (22)(23)(24)(25)(26)(27)30). GRP78 on the plasma membrane functions as a cell surface signaling receptor for activated ␣2-macroglobulin (45).…”

Section: Discussionmentioning

confidence: 99%

“…It is also a critical regulator of ER stress, maintains calcium homeostasis in the ER, acts as an antiapoptotic protein, and plays important roles in angiogenesis and tumor progression (20,21). Besides the ER, GRP78 is also localized to the cell surfaces of several cell types (22)(23)(24)(25)(26)(27). Though some studies suggest that GRP78-interacting proteins may be involved in its transport to the plasma membrane, the exact mechanism is not clear (26,(28)(29)(30).…”

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confidence: 97%

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GRP78 Is an Important Host Factor for Japanese Encephalitis Virus Entry and Replication in Mammalian Cells

Nain

Mukherjee

Karmakar

et al. 2017

J Virol

126

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Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, is the leading cause of viral encephalitis in Southeast Asia with potential to become a global pathogen. Here, we identify glucose-regulated protein 78 (GRP78) as an important host protein for virus entry and replication. Using the plasma membrane fractions from mouse neuronal (Neuro2a) cells, mass spectroscopy analysis identified GRP78 as a protein interacting with recombinant JEV envelope protein domain III. GRP78 was found to be expressed on the plasma membranes of Neuro2a cells, mouse primary neurons, and human epithelial Huh-7 cells. Antibodies against GRP78 significantly inhibited JEV entry in all three cell types, suggesting an important role of the protein in virus entry. Depletion of GRP78 by small interfering RNA (siRNA) significantly blocked JEV entry into Neuro2a cells, further supporting its role in virus uptake. Immunofluorescence studies showed extensive colocalization of GRP78 with JEV envelope protein in virus-infected cells. This interaction was also confirmed by immunoprecipitation studies. Additionally, GRP78 was shown to have an important role in JEV replication, as treatment of cells post-virus entry with subtilase cytotoxin that specifically cleaved GRP78 led to a substantial reduction in viral RNA replication and protein synthesis, resulting in significantly reduced extracellular virus titers. Our results indicate that GRP78, an endoplasmic reticulum chaperon of the HSP70 family, is a novel host factor involved at multiple steps of the JEV life cycle and could be a potential therapeutic target.IMPORTANCE Recent years have seen a rapid spread of mosquito-borne diseases caused by flaviviruses. The flavivirus family includes West Nile, dengue, Japanese encephalitis, and Zika viruses, which are major threats to public health with potential to become global pathogens. JEV is the major cause of viral encephalitis in several parts of Southeast Asia, affecting a predominantly pediatric population with a high mortality rate. This study is focused on identification of crucial host factors that could be targeted to cripple virus infection and ultimately lead to development of effective antivirals. We have identified a cellular protein, GRP78, that plays a dual role in virus entry and virus replication, two crucial steps of the virus life cycle, and thus is a novel host factor that could be a potential therapeutic target.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 97%

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GRP78 Is an Important Host Factor for Japanese Encephalitis Virus Entry and Replication in Mammalian Cells

Nain

Mukherjee

Karmakar

et al. 2017

J Virol

126

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“…The G ORF of BDV encodes an envelope glycoprotein, which overlaps with the upstream M ORF and contains a long intron of a 1,293 nt for expression of the downstream L gene (7,31,32). The G precursor protein, GP, plays a key role in BDV entry into susceptible cells, and the GP1, the N-terminal subunit of GP, is known to be required for receptor recognition and virus entry (14,15,16,19,22). Previous studies suggested that the expression and correct processing of BDV GP are necessary for BDV dissemination in primary cultures of neurons and that neutralizing antibodies against BDV GP completely inhibited virus spread (3).…”

Section: Discussionmentioning

confidence: 99%

A Novel Borna Disease Virus Vector System That Stably Expresses Foreign Proteins from an Intercistronic Noncoding Region

Daito

Fujino

Honda

et al. 2011

J Virol

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Borna disease virus (BDV),Borna disease virus (BDV) belongs to the Bornaviridae family within the nonsegmented, negative-strand RNA viruses and is characterized by highly neurotropic and noncytopathic infection (18,31). Previous studies revealed that BDV infects a wide variety of mammalian species, suggesting that its host range probably includes all warm-blooded animals. The most striking feature of BDV is that it readily establishes a longlasting, persistent infection in the cell nucleus (9, 31). BDV establishes a stable infection without causing apparent cell damage, even in brain cells (8), making this the only animal RNA virus capable of intranuclear parasitism. These features of BDV suggest that this virus could be a promising candidate for an efficient and stable gene delivery system to the central nervous system (CNS).Recent development of the reverse genetics system of BDV revealed that the virus has the capacity to express foreign genes from the 5Ј end of the genome (26). Recombinant BDV (rBDV) with green fluorescent protein (GFP) near the 5Ј end of the genome (rBDV 5ЈGFP) successfully infected, and was propagated in, cultured cells. This study suggested that the 5Ј

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“…Interestingly, M also associates with vRNP in the host cell nucleus, suggesting that M is involved in viral replication or transport of viral components [15]. G is the viral envelope glycoprotein and is involved in BDV entry, involving virion attachment to an unknown receptor and fusion of the viral envelope and cell membrane to release the vRNP into the cell cytoplasm in association with host factors [16][17][18][19][20][21]. X is a multifunctional, non-structural protein that is essential for the viral replication cycle [22], and is known to be a regulator of viral polymerase activity and an inhibitor of apoptosis in the central nervous system [23 -25].…”

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confidence: 99%

Comprehensive analysis of endogenous bornavirus-like elements in eukaryote genomes

Horie

Kobayashi

Suzuki

et al. 2013

Phil. Trans. R. Soc. B

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Bornaviruses are the only animal RNA viruses that establish a persistent infection in their host cell nucleus. Studies of bornaviruses have provided unique information about viral replication strategies and virus–host interactions. Although bornaviruses do not integrate into the host genome during their replication cycle, we and others have recently reported that there are DNA sequences derived from the mRNAs of ancient bornaviruses in the genomes of vertebrates, including humans, and these have been designated endogenous borna-like (EBL) elements. Therefore, bornaviruses have been interacting with their hosts as driving forces in the evolution of host genomes in a previously unexpected way. Studies of EBL elements have provided new models for virology, evolutionary biology and general cell biology. In this review, we summarize the data on EBL elements including what we have newly identified in eukaryotes genomes, and discuss the biological significance of EBL elements, with a focus on EBL nucleoprotein elements in mammalian genomes. Surprisingly, EBL elements were detected in the genomes of invertebrates, suggesting that the host range of bornaviruses may be much wider than previously thought. We also review our new data on non-retroviral integration of Borna disease virus.

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Molecular Chaperone BiP Interacts with Borna Disease Virus Glycoprotein at the Cell Surface

Cited by 61 publications

References 35 publications

GRP78 Is an Important Host Factor for Japanese Encephalitis Virus Entry and Replication in Mammalian Cells

GRP78 Is an Important Host Factor for Japanese Encephalitis Virus Entry and Replication in Mammalian Cells

A Novel Borna Disease Virus Vector System That Stably Expresses Foreign Proteins from an Intercistronic Noncoding Region

Comprehensive analysis of endogenous bornavirus-like elements in eukaryote genomes

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