PRRSV structure, replication and recombination: Origin of phenotype and genotype diversity

Abstract

Porcine reproductive and respiratory disease virus (PRRSV) has the intrinsic ability to adapt and evolve. After 25 years of study, this persistent pathogen has continued to frustrate efforts to eliminate infection of herds through vaccination or other elimination strategies. The purpose of this review is to summarize the research on the virion structure, replication and recombination properties of PRRSV that have led to the extraordinary phenotype and genotype diversity that exists worldwide.

Keywords: Arterivirus; Heteroclite; Porcine reproductive and respiratory syndrome virus; Recombination; Replication; Subgenomic RNA.

Fig. 1

PRRSV genome, transcription, and translation. PRRSV replication progresses by a range of genetic and protein regulatory mechanisms. Expression of the first three-fourths of the 14.9–15.5 kb genome yields 4 known polyproteins (pp1a, pp1a-nsp2N, pp1a-nsp2TF, pp1ab) through two documented programmed RFS (•). Polyproteins are co-translationally and post-translationally processed into at least 16 distinct replicase (accessory) nonstructural proteins (nsps) by four viral encoded proteases PLP1α, PLP1β, PLP2, and SP. Recognized polymerase motifs in pp1b are the RNA dependent RNA polymerase (RdRp), the zinc-finger domain (Z), the helical domain (HEL) and the nidovirus uridylate-specific endoribonuclease (NendoU; U) domain. Canonical structural proteins are expressed exclusively through a set of subgenomic RNAs (sgRNA; 2–7) via a co-terminal discontinuous transcription strategy via a negative-sense strand intermediate.

Fig. 2

Intragenomic homologous recombination during negative strand synthesis (crosshatched bars) to produce sgRNA. The PRRSV genome is represented at the top of the figure. The 189 bp 5′ untranslated of strain VR-2332 is shown as a bar encompassing two discrete regions, the 5′ terminal sequence of 183 bases that differs approximately 5% between strains of the same genotype (gray bar) and the 100% conserved U/GUAACC hexanucleotide on the distal end that serves as the transcription regulatory sequence (TRS; black bar). The PRRSV replicase complex is represented by a multi-point star. (A) Production of conanical sgmRNA. (Step 1) sgRNA synthesis initiates as (−) strand replication (blue bar) from the full-length (+) sense (green bar) genome. RdRp interaction with a TRS either results with a read-through and a continuation of (−) strand replication or, in the case of sgRNA synthesis, (Step 2) disassociation of the replicating strain (body AAUUGG; white body) and (Step 3) re-joining at the 5′ leader TRS (leader AAUUGG; leader–body junction) through sequence complementarity annealing followed by completion of (−) strand sgRNA synthesis. All sgRNAs possess identical 3′ and 5′ termini (see Fig. 1). (Step 4) (−) sense sgRNAs serve as template for generation of (+) sense sgRNA synthesis, required for structural protein translation. (B) Production of heteroclite sgRNA at unconventional leader–body junction sites to express aberrant proteins.

Fig. 3

Intergenomic homologous recombination between two different co-infecting PRRSV strains (green and blue bars) of the same genotype during negative strand synthesis (crosshatched bars). Early studies on coronaviruses suggested that intergenomic recombination could also occur during replication of positive strand RNA. The PRRSV genome is represented at the top of the figure. See legend of Fig. 2 for further detail.