Baculovirus Vectors Induce the Production of Interferons in Swine: Their Potential in the Development of Antiviral Strategies.

Guido Nicolás Molina,Ignacio Otero,Sabrina Amalfi,María Paula Molinari,Oscar Taboga

doi:10.3390/vetsci8110278

Abstract

The huge variety of viruses affecting swine represents a global threat. Since vaccines against highly contagious viruses last several days to induce protective immune responses, antiviral strategies for rapid control of outbreak situations are needed. The baculovirus Autographa californica multiple nucleopolyhedrovirus (AcMNPV), an insect virus, has been demonstrated to be an effective vaccine vector for mammals. Besides the ability to display or transduce heterologous antigens, it also induces strong innate immune responses and provides IFN-mediated protection against lethal challenges with viruses like foot-and-mouth disease virus (FMDV) in mice. Thus, the aim of this study was to evaluate the ability of AcMNPV to induce IFN production and elicit antiviral activity in porcine peripheral blood mononuclear cells (PBMCs). Our results demonstrated that AcMNPV induced an IFN-α-mediated antiviral activity in PBMCs in vitro. Moreover, the inoculation of AcMNPV in piglets led to the production of type I and II IFNs in sera from inoculated animals and antiviral activities against vesicular stomatitis virus (VSV) and FMDV measured by in vitro assays. Finally, it was demonstrated that the pseudotyping of AcMNPV with VSV-G protein, but not the enrichment of the AcMNPV genome with specific immunostimulatory CpG motifs for the porcine TLR9, improved the ability to induce IFN-α production in PBMCs in vitro. Together, these results suggest that AcMNPV is a promising tool for the induction of IFNs in antiviral strategies, with the potential to be biotechnologically improved.

Highlights

Despite the efforts to develop new vaccines against swine infectious diseases, porcine viruses remain a serious threat for animal health and food safety and cause serious economic losses [1,2]
To study the impact of Autographa californica multiple nucleopolyhedrovirus (AcMNPV) on porcine immune cells in terms of the production of this kind of soluble antiviral factors, swine peripheral blood mononuclear cells (PBMCs) purified from blood samples from nine-week-old piglets were selected as an ex vivo model and evaluated IFN production by measuring their antiviral activity
These assays were performed in MDBK cells, since they are frequently used in antiviral assays with porcine IFNs and vesicular stomatitis virus (VSV), and LFBK cells, a porcine cell line sensitive to foot-and-mouth disease virus (FMDV)

Summary

Introduction

Despite the efforts to develop new vaccines against swine infectious diseases, porcine viruses remain a serious threat for animal health and food safety and cause serious economic losses [1,2]. Interferons (IFNs), the main antiviral soluble factors of innate immunity, have been thoroughly studied and even used for the treatment of several human and animal viral diseases [3,4,5,6]. Their direct use in swine and other livestock animals is not profitable, IFN-based antiviral strategies could be promising against epidemic IFN-sensitive viruses like porcine reproductive and respiratory syndrome virus [7], porcine epidemic diarrhea virus [8], African swine fever virus [9], and influenza virus [10,11]. The impact on several of these pattern recognition receptors depends, among other aspects, on the particular sequence [22], and the entry and intracellular trafficking of the molecules [19,23,24,25]

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