Emerging Highly Virulent Porcine Epidemic Diarrhea Virus: Molecular Mechanisms of Attenuation and Rational Design of Live Attenuated Vaccines

Abstract

The highly virulent porcine epidemic diarrhea virus (PEDV) emerged in China in 2010. It infects pigs of all ages, and causes severe diarrhea and high mortality rates in newborn pigs, leading to devastating economic losses in the pork industry worldwide. Effective and safe vaccines against highly virulent PEDV strains are still unavailable, hampering the further prevention, control and eradication of the disease in herds. Vaccination of pregnant sows with live attenuated vaccines (LAVs) is the most effective strategy to induce lactogenic immunity in the sows, which provides A passive protection of suckling piglets against PEDV via the colostrum (beestings, or first milk) and milk. Several LAV candidates have been developed via serially passaging the highly virulent PEDV isolates in non-porcine Vero cells. However, their efficacies in the induction of sufficient protection against virulent PEDV challenge vary in vivo. In this review, we summarize the current knowledge of the virulence-related mutations of PEDV and their potential roles in PEDV attenuation in vivo. With the successful development of reverse genetics systems for PEDV, we also discuss how to use them to generate promising LAV candidates that are safe, effective and genetically stable. This article provides timely insight into the rational design of effective and safe PEDV LAV candidates.

Keywords: attenuation; coronavirus; live attenuated vaccine; porcine epidemic diarrhea virus; virulence.

Figure 1

Schematic organization of the porcine epidemic diarrhea virus (PEDV) genome, polypeptides pp1a and pp1ab. The genome encodes open reading frames 1a (ORF1a) and 1b (ORF1b), followed by the genes encoding spike protein (S), accessory protein 3 (ORF3), envelope protein (E), membrane (M) and nucleocapsid (N) proteins. Translation of ORF1a and 1b results in two polypeptides pp1a and pp1ab, mediated by a −1 frame-shifting signal [5]. The polypeptides are protease-processed into 16 non-structural proteins (nsps). PLpro: Papain-like protease; 3CLpro: 3C-like protease; RdRp: RNA-dependent RNA polymerase; Hel: Helicase; Exon: Exonuclease; MTase: Methyltransferase: EndoU: Endoribonuclease.