Abstract

Pseudorabies virus (PRV) infection of swine can produce Aujeszky’s disease, which causes neurological, respiratory, and reproductive symptoms, leading to significant economic losses in the swine industry. Although humans are not the natural hosts of PRV, cases of human encephalitis and endophthalmitis caused by PRV infection have been reported between animals and workers. Currently, a lack of specific treatments and the emergence of new PRV strains against which existing vaccines do not protect makes the search for effective antiviral drugs essential. As an alternative to traditional nucleoside analogues such as acyclovir (ACV), we studied the antiviral effect of valpromide (VPD), a compound derived from valproic acid, against PRV infection in the PK15 swine cell line and the neuroblastoma cell line Neuro-2a. First, the cytotoxicity of ACV and VPD in cells was compared, demonstrating that neither compound was cytotoxic at a specific concentration range after 24 h exposure. Furthermore, the lack of direct virucidal effect of VPD outside of an infected cell environment was demonstrated. Finally, VPD was shown to have an antiviral effect on the viral production of two strains of pseudorabies virus (wild type NIA-3 and recombinant PRV-XGF) at the concentrations ranging from 0.5 to 1.5 mM, suggesting that VPD could be a suitable alternative to nucleoside analogues as an antiherpetic drug against Aujeszky’s disease.

Highlights

  • Pseudorabies virus (PRV), known as suid herpes virus type 1 (SuHV-1), is a pathogen that belongs to the subfamily Alphaherpesvirinae [1]

  • After 1 h of viral adsorption, cells were washed with PBS and left in culture medium (CM) supplemented with 10% fetal bovine serum (FBS) for 24 h at 37 ◦ C in a humidified atmosphere of

  • Antiviral Effect of ACV and VPD in PK15 Cells Infected with PRV-XGF

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Summary

Introduction

Pseudorabies virus (PRV), known as suid herpes virus type 1 (SuHV-1), is a pathogen that belongs to the subfamily Alphaherpesvirinae [1]. AD is considered to be eradicated from several European countries, the USA, Canada, Mexico, and New Zealand, where the attenuated pseudorabies virus vaccine strain BarthaK61 was preventively applied in massive control campaign. This vaccine, which lacks the genes that encode the glycoproteins gE and gI and harbors other independent mitigating defects was extensively used, but alternative eradication programs used either naturally attenuated or recombinant gG or gC-deleted vaccines [4,17,18]. The use of this antiviral does not protect against the reactivation of the virus in the event that it has established latency [24] and the possibility of co-infection in pigs with PRV and a great variety of both bacterial and viral pathogens makes treatment difficult [6]. PRV in vitro suggests that VPD should be considered to be an antiherpetic drug

Cell Cultures
Viruses
Antibodies and Reagents
Viral Infections
Endpoint Dilution Assay
Immunofluorescence Microscopy
Cell Viability Assay
Virucidal Effect of VPD against PRV
Antiviral Effect of ACV and VPD in PK15 Cells Infected with PRV-XGF
2.10. Immunoblot
VPD and ACV Are Non-Toxic in Neither N2a nor PK15 Cells at Clinically
Infection of PK15 Cells with PRV
VPD Shows No Virucidal Effect against PRV
Antiviral Effect of VPD and ACV on PRV Infection of PK15 Cells
Discussion

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