BiP (GRP78) and Endoplasmin (GRP94) Are Induced following Rotavirus Infection and Bind Transiently to an Endoplasmic Reticulum-Localized Virion Component

Xu, Aimin; Bellamy, A R; Taylor, John A.

doi:10.1128/jvi.72.12.9865-9872.1998

Cited by 78 publications

(40 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been shown that rotavirus infection induces the expression of a large set of genes, including those encoding heat shock proteins hsp90 and hsp70, as well as the glucose regulated proteins grp78 and grp94 (Cuadras et al, 2002;Xu et al, 1998;L. Maruri, unpublished).…”

Section: Rnai To Study Rotavirus-host Cell Interactionsmentioning

confidence: 99%

RNA silencing of rotavirus gene expression

et al. 2004

View full text Add to dashboard Cite

RNA interference (RNAi) is a double-stranded RNA (dsRNA)-triggered mechanism for suppressing gene expression, which is conserved in evolution and has emerged as a powerful tool to study gene function. Rotaviruses, the leading cause of severe diarrhea in young children, are formed by three concentric layers of protein, and a genome composed of 11 segments of dsRNA. Here, we show that the RNAi machinery can be triggered to silence rotavirus gene expression by sequence-specific short interfering RNAs (siRNAs). RNAi is also useful for the study of the virus-cell interactions, through the silencing of cellular genes that are potentially important for the replication of the virus. Interestingly, while the translation of mRNAs is readily stopped by the RNAi machinery, the viral transcripts involved in virus genome replication do not seem to be susceptible to RNAi. Since gene silencing by RNAi is very efficient and specific, this system could become a novel therapeutic approach for rotavirus and other virus infections, once efficient methods for in vivo delivery of siRNAs are developed. Although the use of RNAi as an antiviral therapeutic tool remains to be demonstrated, there is no doubt that this technology will influence drastically the way postgenomic virus research is conducted.

show abstract

Section: Rnai To Study Rotavirus-host Cell Interactionsmentioning

confidence: 99%

RNA silencing of rotavirus gene expression

et al. 2004

View full text Add to dashboard Cite

show abstract

“…As noted in the Introduction section, the expression of GRP78 is essential for replication and productive virus release for many "well known" pathogenic viruses such as Ebola; Cytomegalovirus; Chikungunya, Measles; HIV; Influenza; Lassa; and Marburg (Roux, 1990;Earl et al, 1991;Moreno and Tiffany-Castiglioni, 2014;Anderson et al, 1992;Hogue and Nayak, 1992;Xu et al, 1997;Carleton and Brown, 1997;Xu et al, 1998;Bolt, 2001;Bredèche et al, 2001;Shen et al, 2002;Dimcheff et al, 2004;He, 2006;Spurgers et al, 2010;Reid et al, 2014). Some viruses such as Dengue fever virus are reported to actually infect cells through a cell surface expressed GRP78 protein (Quinones et al, 2008).…”

Section: Journal Of Cellular Physiologymentioning

confidence: 99%

“…GRP78, as a chaperone, also plays an important role in the protein folding processes that occur in the ER including during cancer, liver disease and virus replication. The prokaryotic homologue of GRP78, Dna K, also plays an essential role in bacterial cell biology where it chaperones proteins such as Rec A which is essential for bacterial DNA replication and resistance where engulfed to the respiratory burst of macrophages (Roux, 1990;Earl et al, 1991;Anderson et al, 1992;Hogue and Nayak, 1992;Xu et al, 1997;Carleton and Brown, 1997;Xu et al, 1998;Bolt, 2001;Shen et al, 2002;Dimcheff et al, 2004;He, 2006;Reid et al, 2014;Moreno and Tiffany-Castiglioni, 2014;Spurgers et al, 2010;Bredeche et al, 2001). When high levels of unfolded protein are present in the ER, e.g.…”

mentioning

confidence: 99%

GRP78/BiP/HSPA5/Dna K is a universal therapeutic target for human disease

et al. 2015

View full text Add to dashboard Cite

The chaperone GRP78/Dna K is conserved throughout evolution down to prokaryotes. The GRP78 inhibitor OSU-03012 (AR-12) interacted with sildenafil (Viagra) or tadalafil (Cialis) to rapidly reduce GRP78 levels in eukaryotes and as a single agent reduce Dna K levels in prokaryotes. Similar data with the drug combination were obtained for: HSP70, HSP90, GRP94, GRP58, HSP27, HSP40 and HSP60. OSU-03012/sildenafil treatment killed brain cancer stem cells and decreased the expression of: NPC1 and TIM1; LAMP1; and NTCP1, receptors for Ebola/Marburg/Hepatitis A, Lassa fever, and Hepatitis B viruses, respectively. Pre-treatment with OSU-03012/sildenafil reduced expression of the coxsakie and adenovirus receptor in parallel with it also reducing the ability of a serotype 5 adenovirus or coxsakie virus B4 to infect and to reproduce. Similar data were obtained using Chikungunya, Mumps, Measles, Rubella, RSV, CMV, and Influenza viruses. OSU-03012 as a single agent at clinically relevant concentrations killed laboratory generated antibiotic resistant E. coli and clinical isolate multi-drug resistant N. gonorrhoeae and MRSE which was in bacteria associated with reduced Dna K and Rec A expression. The PDE5 inhibitors sildenafil or tadalafil enhanced OSU-03012 killing in N. gonorrhoeae and MRSE and low marginally toxic doses of OSU-03012 could restore bacterial sensitivity in N. gonorrhoeae to multiple antibiotics. Thus, Dna K and bacterial phosphodiesterases are novel antibiotic targets, and inhibition of GRP78 is of therapeutic utility for cancer and also for bacterial and viral infections. J. Cell. Physiol. 230: 1661–1676, 2015. © 2014 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.

show abstract

“…NSP4-EGFP enters an alternative pathway labeled by the autophagosomal marker LC3. Xu et al (30) reported that rotavirus infection, as well as the transient expression of NSP4 alone, upregulates the expression of the ER-localized chaperones BiP and endoplasmin. The authors attributed this phenomenon to ER stress.…”

Section: Glycosylated Nsp4-egfp Protein Is Expressed In Inducible Cellsmentioning

confidence: 99%

Rotavirus NSP4 Induces a Novel Vesicular Compartment Regulated by Calcium and Associated with Viroplasms

Berkova

Crawford

Trugnan

et al. 2006

J Virol

113

View full text Add to dashboard Cite

Rotavirus is a major cause of infantile viral gastroenteritis. Rotavirus nonstructural protein 4 (NSP4) has pleiotropic properties and functions in viral morphogenesis as well as pathogenesis. Recent reports show that the inhibition of NSP4 expression by small interfering RNAs leads to alteration of the production and distribution of other viral proteins and mRNA synthesis, suggesting that NSP4 also affects virus replication by unknown mechanisms. This report describes studies aimed at correlating the localization of intracellular NSP4 in cells with its functions. To be able to follow the localization of NSP4, we fused the C terminus of full-length NSP4 with the enhanced green fluorescent protein (EGFP) and expressed this fusion protein inducibly in a HEK 293-based cell line to avoid possible cytotoxicity. NSP4-EGFP was initially localized in the endoplasmic reticulum (ER) as documented by Endo H-sensitive glycosylation and colocalization with ER marker proteins. Only a small fraction of NSP4-EGFP colocalized with the ER-Golgi intermediate compartment (ERGIC) marker ERGIC-53. NSP4-EGFP did not enter the Golgi apparatus, in agreement with the Endo H sensitivity and a previous report that secretion of an NSP4 cleavage product generated in rotavirus-infected cells is not inhibited by brefeldin A. A significant population of expressed NSP4-EGFP was distributed in novel vesicular structures throughout the cytoplasm, not colocalizing with ER, ERGIC, Golgi, endosomal, or lysosomal markers, thus diverging from known biosynthetic pathways. The appearance of vesicular NSP4-EGFP was dependent on intracellular calcium levels, and vesicular NSP4-EGFP colocalized with the autophagosomal marker LC3. In rotavirus-infected cells, NSP4 colocalized with LC3 in cap-like structures associated with viroplasms, the site of nascent viral RNA replication, suggesting a possible new mechanism for the involvement of NSP4 in virus replication.Rotavirus causes an age-dependent and potentially lifethreatening dehydrating viral gastroenteritis in small animals and young children worldwide. The mechanism of rotavirusinduced diarrhea is not fully understood, but it is caused in part by the first described viral enterotoxin-rotavirus nonstructural protein 4 (NSP4) (3, 11). NSP4 has pleiotropic properties in cells related to its involvement in both rotavirus pathogenesis and morphogenesis (reviewed in references 4 and 11). Peritoneal injection or luminal administration of NSP4 into 6-to 10-day-old mice causes an age-and dose-dependent diarrhea within hours after inoculation. This diarrhea is due to extracellular NSP4 stimulating a transient, receptor-mediated phospholipase C activation, leading to elevated intracellular calcium levels and subsequent chloride secretion (3,8,22). Further studies have shown that a 66-amino-acid (aa) NSP4 cleavage product, which retains enterotoxigenic activity, is secreted into the media of rotavirus-infected cells early postinfection by a brefeldin A resistant mechanism, suggesting the existence of a nonclassical pa...

show abstract

BiP (GRP78) and Endoplasmin (GRP94) Are Induced following Rotavirus Infection and Bind Transiently to an Endoplasmic Reticulum-Localized Virion Component

Cited by 78 publications

References 41 publications

RNA silencing of rotavirus gene expression

RNA silencing of rotavirus gene expression

GRP78/BiP/HSPA5/Dna K is a universal therapeutic target for human disease

Rotavirus NSP4 Induces a Novel Vesicular Compartment Regulated by Calcium and Associated with Viroplasms

Contact Info

Product

Resources

About