scholarly journals Antioxidant Effect of A. chilensis on the Production of Infectious Viral Particles of ISAv and Its Consequences on the SUMOylation of NP Protein

Proceedings ◽  
2020 ◽  
Vol 50 (1) ◽  
pp. 11
Author(s):  
Fernanda Fredericksen ◽  
Gardenia Payne ◽  
Nicolás Maldonado ◽  
Melina Villalba ◽  
Víctor Olavarría

Infectious salmon anemia virus (ISAv) is a pathogen of high economic importance worldwide; it produces a highly fatal clinical symptomatology called infectious salmon anemia (ISA), which is one of the main causes of economic loss in Chilean aquaculture, specifically in Chilean salmon, being responsible for a mortality rate greater than 80% when outbreaks of this pathogen occur in fish farms. ISAv dramatically increases levels of reactive oxygen species (ROS) by increasing the activity of the p38MAPK protein, which activates p47phox, by phosphorylation, allowing its binding to the membrane subunits of the NADPH oxidase complex, which is an important positive regulator of ROS levels in cells. Further, it is known that oxidative stress is able to regulate the SUMOylation machinery, producing an increase in SUMOylated proteins. Together with this background and various bioinformatic analyses, it was found that the ISAv nucleoprotein (NP) has a highly conserved capacity for SUMOylation, and this protein alone is capable of causing strong oxidative stress in transfected cells and is therefore able to regulate the SUMOylation machinery. Immunoprecipitation assays confirmed the bioinformatic analyses, where NP was seen to be SUMOylated, and this signal decreased considerably when cells were treated with a p38MAPK inhibitor. Together with this, the number of copies of NP and the viability in cells infected with ISAv were also evaluated, where it was observed that there was a strong increase in the number of copies of NP and a marked decrease in cell viability, this being in contrast to when, in addition to the infection, the cells were treated with a natural product “maqui” (A. chilensis), which, due to its high content of polyphenolic compounds, has been shown to have a high antioxidant capacity, greatly reducing the number of copies of NP and the percentage of mortality compared to cells that are only infected with ISAv.

2011 ◽  
Vol 85 (16) ◽  
pp. 8037-8045 ◽  
Author(s):  
A. Rivas-Aravena ◽  
E. Vallejos-Vidal ◽  
M. Cortez-San Martin ◽  
F. Reyes-Lopez ◽  
M. Tello ◽  
...  

2016 ◽  
Vol 82 (8) ◽  
pp. 2563-2571 ◽  
Author(s):  
Nicolás Ojeda ◽  
Constanza Cárdenas ◽  
Fanny Guzmán ◽  
Sergio H. Marshall

ABSTRACTInfectious salmon anemia virus (ISAV) is the etiological agent of the disease by the same name and causes major losses in the salmon industry worldwide. Epizootic ISAV outbreaks have occurred in Norway and, to a lesser degree, in Canada. In 2007, an ISAV outbreak in Chile destroyed most of the seasonal production and endangered the entire Chilean salmon industry. None of the existing prophylactic approaches have demonstrated efficacy in providing absolute protection from or even a palliative effect on ISAV proliferation. Sanitary control measures for ISAV, based on molecular epidemiology data, have proven insufficient, mainly due to high salmon culture densities and a constant presence of a nonpathogenic strain of the virus. This report describes an alternative treatment approach based on interfering peptides selected from a phage display library. The screening of a phage display heptapeptide library resulted in the selection of a novel peptide with significantin vitroantiviral activity against ISAV. This peptide specifically interacted with the viral hemagglutinin-esterase protein, thereby impairing virus binding, with plaque reduction assays showing a significant reduction in viral yields. The identified peptide acts at micromolar concentrations against at least two different pathogenic strains of the virus, without detectable cytotoxic effects on the tested fish cells. Therefore, antiviral peptides represent a novel alternative for controlling ISAV and, potentially, other fish pathogens.IMPORTANCEIdentifying novel methods for the efficient control of infectious diseases is imperative for the future of global aquaculture. The present study used a phage display heptapeptide library to identify a peptide with interfering activity against a key protein of the infectious salmon anemia virus (ISAV). A piscine orthomyxovirus, ISAV is a continuous threat to the commercial sustainability of cultured salmon production worldwide. The complex epidemiological strategy of this pathogen has made prophylactic control extremely difficult. The identified antiviral peptide efficiently impairs ISAV infectionin vitroby specifically blocking hemagglutinin-esterase, a pivotal surface protein of this virus. Peptide synthesis could further modify the primary structure of the identified peptide to improve specific activity and stability. The present results form the foundation for developing a new pharmacological treatment against ISAV.


2017 ◽  
Vol 114 (14) ◽  
pp. E2929-E2936 ◽  
Author(s):  
Jonathan D. Cook ◽  
Azmiri Sultana ◽  
Jeffrey E. Lee

Orthomyxoviruses are an important family of RNA viruses, which include the various influenza viruses. Despite global efforts to eradicate orthomyxoviral pathogens, these infections remain pervasive. One such orthomyxovirus, infectious salmon anemia virus (ISAV), spreads easily throughout farmed and wild salmonids, constituting a significant economic burden. ISAV entry requires the interplay of the virion-attached hemagglutinin-esterase and fusion glycoproteins. Preventing infections will rely on improved understanding of ISAV entry. Here, we present the crystal structures of ISAV hemagglutinin-esterase unbound and complexed with receptor. Several distinctive features observed in ISAV HE are not seen in any other viral glycoprotein. The structures reveal a unique mode of receptor binding that is dependent on the oligomeric assembly of hemagglutinin-esterase. Importantly, ISAV hemagglutinin-esterase receptor engagement does not initiate conformational rearrangements, suggesting a distinct viral entry mechanism. This work improves our understanding of ISAV pathogenesis and expands our knowledge on the overall diversity of viral glycoprotein-mediated entry mechanisms. Finally, it provides an atomic-resolution model of the primary neutralizing antigen critical for vaccine development.


Sign in / Sign up

Export Citation Format

Share Document