VER-155008 induced Hsp70 proteins expression in fish cell cultures while impeding replication of two RNA viruses

Pham, Phuc H.; Sokeechand, Bibi S.H.; Hamilton, Mark E.; Misk, Ehab; Jones, Ginny; Lee, Lucy E. J.; Lumsden, John S.; Bols, Niels C.

doi:10.1016/j.antiviral.2019.01.001

Cited by 12 publications

(6 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To overcome the confounding effects of functional redundancy between Hsc70 and Hsp70 and further examine at which stages of the viral life cycle their involvement is needed, we first employed two inhibitors of Hsp70s, VER155008 (Pham et al., 2019) and quercetin (Chen et al., 2022; Ogawa et al., 2014) to inhibit Hsc70 and Hsp70 simultaneously. Cell viability assays indicated that 40 μM quercetin and 2 μM VER155008 had no cytotoxicity in WRD cells (data not shown), and the concentrations were used for subsequent studies.…”

Section: Resultsmentioning

confidence: 99%

Chaperones Hsc70 and Hsp70 play distinct roles in the replication of bocaparvovirus minute virus of canines

Guo,

Yan,

Sun

et al. 2024

Molecular Microbiology

View full text Add to dashboard Cite

Minute virus of canines (MVC) belongs to the genus Bocaparvovirus (formerly Bocavirus) within the Parvoviridae family and causes serious respiratory and gastrointestinal symptoms in neonatal canines worldwide. A productive viral infection relies on the successful recruitment of host factors for various stages of the viral life cycle. However, little is known about the MVC‐host cell interactions. In this study, we identified that two cellular proteins (Hsc70 and Hsp70) interacted with NS1 and VP2 proteins of MVC, and both two domains of Hsc70/Hsp70 were mediated for their interactions. Functional studies revealed that Hsp70 was induced by MVC infection, knockdown of Hsc70 considerably suppressed MVC replication, whereas the replication was dramatically promoted by Hsp70 knockdown. It is interesting that low amounts of overexpressed Hsp70 enhanced viral protein expression and virus production, but high amounts of Hsp70 overexpression weakened them. Upon Hsp70 overexpressing, we observed that the ubiquitination of viral proteins changed with Hsp70 overexpression, and proteasome inhibitor (MG132) restored an accumulation of viral proteins. In addition, we verified that Hsp70 family inhibitors remarkably decreased MVC replication. Overall, we identified Hsc70 and Hsp70 as interactors of MVC NS1 and VP2 proteins and were involved in MVC replication, which may provide novel targets for anti‐MVC approach.

show abstract

Section: Resultsmentioning

confidence: 99%

Chaperones Hsc70 and Hsp70 play distinct roles in the replication of bocaparvovirus minute virus of canines

Guo,

Yan,

Sun

et al. 2024

Molecular Microbiology

View full text Add to dashboard Cite

show abstract

“…This molecule shows potent anticancer activity as well as antiviral properties (Baquero-P erez & Whitehouse 2015). This compound was tested against VHSV and IPNV in fish cell lines, and the results revealed that the replication of both viruses was significantly reduced by VER-155008 (Pham et al 2019). On the other hand, geldanamycin, with affinity for the ATPbinding pocket of HSP90, also shows antitumour and antiviral properties (Li et al 2010a).…”

Section: Protein Synthesis Post-translational Modifications Virion As...mentioning

confidence: 99%

Compilation of antiviral treatments and strategies to fight fish viruses

Pereiro

Figueras

Novoa

2020

Reviews in Aquaculture

View full text Add to dashboard Cite

The implementation of antiviral treatments and prophylaxis strategies in fish aquaculture needs to be established. The absence of commercial vaccines for most viral diseases affecting economically relevant fish species, and the total lack of treatments to fight these diseases once they have emerged in a fish farm remains one of the main bottlenecks in fish aquaculture production. However, although no antivirals are currently applied on farms, a great number of investigations have been conducted to assess the potential use of antiviral treatments against several fish viruses. Although most of these works were based on in vitro approaches, some included in vivo experiments to demonstrate the potential applicability of these treatments. This review summarizes the investigations conducted both in vitro and in vivo in the field of antiviral treatments against fish viruses. The highlighted works include those using piscine and non-piscine proteins with antimicrobial functions, metabolites, chemical compounds (some of which are used in medicine to treat human viruses), bioactive compounds mainly isolated from plants and bacteria, and emerging DNA-and RNA-based therapeutics. This information can be used for developing both specific and broad-spectrum antiviral strategies to be further used in the aquaculture industry, and it may even provide interesting indications for biomedical research.

show abstract

“…The Hsp70 is thus predicted to act as a broad‐spectrum antiviral target (Shan et al, 2018). Although a drug targeting Hsp70 function has been investigated with two fish viruses, viral haemorrhagic septicaemia virus (VHSV) and infectious pancreatic necrosis virus (IPNV) (Pham et al, 2019), no antiviral potential of any drugs targeting Hsp70 expression had been tested against any aquatic animal virus till now (Pham et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Quercetin counteracts the pro‐viral effect of heat shock response in grass carp cells with its therapeutic potential against aquareovirus

Wang

et al. 2021

Aquaculture Research

View full text Add to dashboard Cite

We have previously shown that heat shock protein (Hsp70) is significantly up‐regulated by grass carp reovirus (GCRV) infection, and Hsp70 plays a positive role in facilitating GCRV infection in vitro through unknown mechanisms. Considering the fact that Hsp70 is the most highly induced heat shock protein in cells undergoing the conserved heat shock response (HSR), we determined here that both aquareovirus infection and heat shock induced expression of Hsp70 in grass carp ctenopharyngodon idella kidney cell line (CIK). The pro‐viral function of heat shock response was associated with the involvement of Hsp70 in the replication and transcription complex (RTC) of GCRV104 as shown by co‐localization of Hsp70 with viral double‐stranded RNA (dsRNA). Furthermore, we evaluated the potential of grass carp Hsp70 as a novel fish antiviral target through its down‐regulation by plant‐derived quercetin, a major dietary flavonoid and known mammalian transcriptional repressor for heat shock factor 1 (HSF‐1). In the presence of 50 µM quercetin, grass carp Hsp70 expression was significantly suppressed in cells stressed with either GCRV‐104 infection or heat shock. Reduced viral protein expression and descendent virions correlated with the down‐regulation of Hsp70 by quercetin in GCRV104‐infected grass carp cells, and the pro‐viral effect of heat shock could be counteracted by quercetin, which highlighted the involvement of heat shock response protein Hsp70 as a quercetin‐mediated antiviral target. Antiviral effects of quercetin in a dose‐dependent manner were also observed for GCRV JX‐01, a different genotype of GCRV, which predicted a broad‐spectrum nature of quercetin in suppressing aquareovirus replication. Overall, the data here indicated that quercetin acted as a specific suppressor for grass carp Hsp70 expression in cells stressed with either aquareovirus or heat shock, and the suppressing effect of quercetin on aquareovirus infection implied its potential as an environmental‐friendly and broad‐spectrum antiviral drug through targeting fish heat shock response protein.

show abstract

VER-155008 induced Hsp70 proteins expression in fish cell cultures while impeding replication of two RNA viruses

Cited by 12 publications

References 66 publications

Chaperones Hsc70 and Hsp70 play distinct roles in the replication of bocaparvovirus minute virus of canines

Chaperones Hsc70 and Hsp70 play distinct roles in the replication of bocaparvovirus minute virus of canines

Compilation of antiviral treatments and strategies to fight fish viruses

Quercetin counteracts the pro‐viral effect of heat shock response in grass carp cells with its therapeutic potential against aquareovirus

Contact Info

Product

Resources

About