Hsp70 Is a Potential Therapeutic Target for Echovirus 9 Infection

Abstract

Echovirus is an important cause of viral pneumonia and encephalitis in infants, neonates, and young children worldwide. However, the exact mechanism of its pathogenesis is still not well understood. Here, we established an echovirus type 9 infection mice model, and performed two-dimensional gel electrophoresis (2DE) and tandem mass spectrometry (MS/MS)-based comparative proteomics analysis to investigate the differentially expressed host proteins in mice brain. A total of 21 differentially expressed proteins were identified by MS/MS. The annotation of the differentially expressed proteins by function using the UniProt and GO databases identified one viral protein (5%), seven cytoskeletal proteins (33%), six macromolecular biosynthesis and metabolism proteins (28%), two stress response and chaperone binding proteins (9%), and five other cellular proteins (25%). The subcellular locations of these proteins were mainly found in the cytoskeleton, cytoplasm, nucleus, mitochondria, and Golgi apparatus. The protein expression profiles and the results of quantitative RT-PCR in the detection of gene transcripts were found to complement each other. The differential protein interaction network was predicted using the STRING database. Of the identified proteins, heat shock protein 70 (Hsp70), showing consistent results in the proteomics and transcriptomic analyses, was analyzed through Western blotting to verify the reliability of differential protein expression data in this study. Further, evaluation of the function of Hsp70 using siRNA and quercetin, an inhibitor of Hsp70, showed that Hsp70 was necessary for the infection of echovirus type 9. This study revealed that echovirus infection could cause the differential expression of a series of host proteins, which is helpful to reveal the pathogenesis of viral infection and identify therapeutic drug targets. Additionally, our results suggest that Hsp70 could be a useful therapeutic host protein target for echovirus infection.

Cell-Specific Transposable Element Gene Expression Analysis Identifies Associations with Systemic Lupus Erythematosus Phenotypes

“…Some of the top upregulated genes are ISG15, IFIT3, IRF7, and BST2 which play roles in response to viruses. In NK cells there are many up and down regulated genes as seen in 6D, some of the top upregulated genes are NXF1 , which is involved in transport of unspliced retroviral genomic RNA and CAPZA1 which was downregulated, and is also observed to be downregulated in virus infected cells(24, 25).…”

Heat shock protein 70, glutamate dehydrogenase, and angiotensin-converting enzyme of Bombyx mori mediate the cell attachment of Cypovirus 1

“…Tembusu virus [43], enterovirus 71 [44], and echovirus 9 [45], in which HSP70 functioned as receptor, supplemental receptor, or accessory factor that facilitates viral binding to host cells and viral entry. Based on the findings of this study, we suggest that HSP70 of B. mori could be employed by DpCPV to facilitate viral attachment and cell entry.…”

“…HSP70 is a 70 kDa housekeeping protein chaperone located on the cell surface of several prokaryotes and eukaryotes cells, and it is responsible for assuring nascent protein folding, refolding misfolded proteins, and facilitating protein transportation [36]. Research indicated that HSP70 contributes to the attachment and cell entry of multiple viruses such as rotavirus [21], dengue virus [37], Japanese encephalitis virus [38], Marek’s disease virus [39], Hazara virus [40], Chikungunya virus [41], grass carp reovirus [42], Tembusu virus [43], enterovirus 71 [44], and echovirus 9 [45], in which HSP70 functioned as receptor, supplemental receptor, or accessory factor that facilitates viral binding to host cells and viral entry. Based on the findings of this study, we suggest that HSP70 of B. mori could be employed by DpCPV to facilitate viral attachment and cell entry.…”

Molecular detection and phylogenetic tree of echovirus in children at Thi-Qar province Iraq

“…However, depending on the virus type, its effects on host protein expression, and physiological metabolism, they can be severe and life-threatening (Wang et al 2020). Echovirus infections affect infants and neonates the most, with echoviruses accounting for the majority of Enterovirus infections in newborns under the age of two months , in Neonatal Intensive Care Unit (NICU) outbreaks, Echovirus infections are extremely dangerous, accounting for 15-30% of nosocomial viral infections and resulting in neonatal death in up to 25% of cases (Civardi et al 2013).…”