Key Gaps in the Knowledge of the Porcine Respiratory Reproductive Syndrome Virus (PRRSV)

Abstract

The porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important swine diseases in the world. It is causing an enormous economic burden due to reproductive failure in sows and a complex respiratory syndrome in pigs of all ages, with mortality varying from 2 to 100% in the most extreme cases of emergent highly pathogenic strains. PRRSV displays complex interactions with the immune system and a high mutation rate, making the development, and implementation of control strategies a major challenge. In this review, the biology of the virus will be addressed focusing on newly discovered functions of non-structural proteins and novel dissemination mechanisms. Secondly, the role of different cell types and viral proteins will be reviewed in natural and vaccine-induced immune response together with the role of different immune evasion mechanisms focusing on those gaps of knowledge that are critical to generate more efficacious vaccines. Finally, novel strategies for antigen discovery and vaccine development will be discussed, in particular the use of exosomes (extracellular vesicles of endocytic origin). As nanocarriers of lipids, proteins and nucleic acids, exosomes have potential effects on cell activation, modulation of immune responses and antigen presentation. Thus, representing a novel vaccination approach against this devastating disease.

Keywords: PRRSV; extracellular vesicles; immunology; porcine reproductive and respiratory syndrome virus; vaccinology; virus biology.

Figure 1

Genome structure and mature viral particle of PRRSV virus. (A) Non-structural proteins are located in the 5′ end of the genome, codifying for two different polyproteins pp1a and pp1ab that are cleaved into at least 14 nsps (nsp1 to nsp12 and nsp1α and nsp1β, and nsp7α, and nsp7β). Structural proteins located near the 3′ end, are associated to the viral envelope and RNA packaging. (B) PRRSV mature viral particle, composed of a lipid bilayer envelop with viral receptor glycoproteins involved on infection and cell internalization. Single stranded positive RNA is associated with nucleocapsid protein in the internal layer of the virus.

Figure 2

Interactions between viral proteins and cell receptors for virus attachment, entry, uncoating and release of genetic ssRNA to cell cytoplasm. Blocking CD163, CD151 tetraspanin or vimentin seems to inhibit viral replication or infection in the host cell, but reduced replication or no effect is seen when receptors such as heparan-sulfate or siglec-1 are blocked, demonstrating that some viral proteins and cell receptors are indispensable in terms of production of infectious viral progeny and dissemination in the host.