Porcine reproductive and respiratory syndrome (PRRS) caused by the porcine reproductive and respiratory syndrome (PRRS) virus (Betaarterivirus types 1 and 2) is one of the most economically significant porcine diseases in many countries of the world: the global annual damage associated with this infection is estimated at more than 600 million US dollars. First outbreaks of the unknown disease were reported in the USA and Western Europe in the late 1980s and early 1990s, turning into a pandemic a few years later [1][2]. Sows exhibited such reproductive failures as abortions, fetal mummification, stillbirths or birth of non-viable offspring, and growing piglets – respiratory manifestations (dyspnea, coughing and hyperthermia) [3] As it was established in the Netherlands in 1991, and later in the USA (in 1992), the disease was caused by the previously unknown RNA-containing virus. The disease came to be known as “porcine reproductive and respiratory syndrome” [4]. Retrospective research suggested that antibodies to PRRS pathogen had been detected before 1979 in Eastern Canada and in the mid-1980s in Iowa [5], but the viruses themselves were not identified. Presumably there were several critical epizootic milestones in the history of PRRS virus (PRRSV) dissimination, and therefore the origin of some strains, in particular from the cluster associated with MN184 strain [6], causing “acute PRRS” or “abortion storm” [7], and some highly pathogenic Chinese strains, remains unknown [8]. In Russia, the first PRRS outbreak was reported in 1991 following abortions in sows on the farms of the Kursk Oblast [9]. In 2007, during a PRRS outbreak in the Irkutsk Oblast, American genotype PRRSV-2 was isolated [10].

The causative agent is PRRSV, which is a small, enveloped positive-sense single-stranded RNA virus belonging to the genus Betaarterivirus, family Arteriviridae, order Nidovirales [11]. PRRSV strains are classified as PRRSV type 1 (European genotype – EU-like) and PRRSV type 2 (North American genotype – NA-like). The virus genome is characterized by high variability even if compared to other RNA viruses. Since the virus RNA-dependent RNA-polymerase lacks proofreading activity, the virus undergoes frequent mutations and recombination events resulting in occurrence of new virus isolates worldwide [12]. Having a length of about 14.9–15.5 kb, the viral genome contains at least 11 open reading frames (ORFs) with a 5’ cap and 3’ polyadenylated tail [13]. Non-structural proteins (nsp 1–12), which have the functions of protease, replicase, regulation of gene expression of the host cell and are responsible for the viral RNA synthesis, are encoded by ORF1a and ORF1b, which occupy approximately two thirds of the genome [14]. Structural proteins – capsid protein (N), membrane protein (M), glycoproteins GP2, GP3, GP4, GP5, and envelope protein (E) – are expressed by subgenomic RNA and encoded by ORF2–7 [15]. Differences in nucleotide sequences of most conserved (ORF7 gene encoding capsid protein N) and variable (ORF5 gene encoding major glycoprotein GP5) form the basis of the current PRRSV genotyping system [16].

Despite multiple sequences deposited in databases, none of the existing classification systems covers diversity of the existing PRRSV variants [17]. Incomplete coverage of the available data and lack of reference sequences are the main shortcomings of the applied genotyping techniques [18]. In 2010, a phylogenetic lineage-based PRRSV typing system was proposed [19]. According to this system, PRRSV-1 strains are grouped into four subtypes (subtype 1 – global, subtype 1 – Russian, subtypes 2 and 3), and PRRSV-2 strains are grouped into nine lineages (lineage 1 – lineage 9) based on phylogenetic relationships in the ORF5 region [20][21]. Both genotypes, divided into clades, lineages, and sub-strains, exhibit high genetic diversity and possess approximately 60% nucleotide sequence identity [22][23] (Table 1).

The objective of this analytical study was to review and summarize current approaches to the laboratory diagnosis and specific prevention of PRRS.

In the nomenclature of the World Organisation for Animal Health, PRRS is classified as a socially and economically significant disease [10]. According to the information provided, infection caused by PRRSV-2 is of greater epidemic importance, since viremia in animals infected with the strains of this genotype was more pronounced and prolonged than in those ones infected with PRRSV-1 [29]. PRRSV-1-1 isolates, including the so-called Russian group of viruses, PRRSV-1-2 and PRRSV-1-3 differ significantly in pathogenicity [3]. The phylogenetic analysis indicates that the European type of virus, mainly belonging to subtype 1 (Russian), is predominantly prevalent in Russia [29]. Most PRRSV-1 strains can be attributed to the Russian group; a small number of circulating strains homologous to Lelystad strain are probably associated with the use of attenuated vaccines based on PRRSV-1 [30]. However, during the PRRS outbreak in the Central Federal District in 2020, in addition to the viruses from the Russian group previously detected in these regions, Lelystad-like viruses were also detected [9][31]. A virus phylogenetically closely related to this type was identified in Poland in 2010 [32]; this indicates that new PRRSV variants from Europe are still introduced into Russia. Until the mid-2000s, the North American PRRSV genotype had not been registered in Russia, but in 2007 an outbreak was recorded in the Irkutsk Oblast caused by high pathogenicity PRRSV-2, presumably brought in from China [33]. In addition, there is information about detection of PRRSV-2 in the Republic of Mordovia, Belgorod and Kemerovo Oblasts [3, 9, 34]. The origin of American strain introduction to the Russian territory has not been identified, but it is assumed that they could have been introduced, for example, from Denmark, where PRRSV-2 circulates and from where breeding animals are imported [9].

The disease is mainly manifested by reproductive disorders in sows, i.e. abortions in late pregnancy, early or delayed farrowing, birth of weak or non-viable piglets, irregular estrus; pathologies in early and middle pregnancy are less often reported [35][36]. The primary cause of the reproductive disorders is virus-induced damage to the placenta and endometrium. Piglets and fattening pigs have respiratory distress syndrome: coughing, sneezing, dyspnea and stunted growth. In addition, PRRSV infection undermines respiratory immunity, which makes infected pigs more susceptible to secondary infections; as a result, bacterial pathogens manifest themselves in association with the viruses, thus, increasing livestock mortality [37]. The young animals are more susceptible to PRRSV than the adults are, while replacement boars and sows often suffer from subclinical infection [38].

The main methods used for PRRS diagnostics are given in Table 2.

No ideal anti-PRRS vaccine has been developed so far. According to the modern requirements for a new generation of vaccines against PRRS, they shall demonstrate high efficacy, safety, and at the same time ensure cross-protection against different genotypes of the virus [44]. Due to the exceptional ability of PRRS to mutate and generate significant genetic variations, development of a broadly protective vaccine is particularly crucial for combating constantly emerging disease outbreaks [45].

The first commercially available modified live attenuated anti-PRRS vaccine (PRRSV-MLV) was released in the USA, in 1994. This event became a starting point for the vaccine large-scale safety and efficacy tests [46]. A significant number of conventional (live and inactivated) vaccines have been developed by now; their brief description is given in Table 3.

Studies demonstrating circulation and persistence of the vaccine virus, in turn, raise concerns about its safety: viremia implies potential transmission of the vaccine virus to non-infected animals. In addition, the vaccine virus can cross the placental barrier in pregnant sows and infect developing fetuses, resulting in the pathogen transmission to uninfected newborn piglets during lactation. It has also been shown that vaccine strains are able to recombine with field strains, creating potentially new genetically distinct variants of PRRSV on individual farms [51]. For these reasons, efficacy of live attenuated vaccines is somewhat controversial, and it is generally recognized that their safety needs to be improved. In this context, DIVA strategy (differentiation of infected from vaccinated animals) will be of great importance for control and possible eradication of PRRS [52][53]. Epizootological and regulatory considerations indicate the need to develop anti-PRRS DIVA vaccine, which will be characterized by a negative marker (that is, a marker absent in the vaccine strain, but permanently present in wild-type strains). Similar candidate vaccines have been developed on the platform of large DNA viruses such as pseudorabies virus (PRV) and bovine herpesvirus type 1 (BHV-1) by deleting genes encoding some structural proteins. However, in case of a small RNA virus such as PRRSV, which encodes only a few proteins with basic functions, the creation of a mutant virus with a deletion of the immunodominant and conserved protein segments (or with a combination of deletions within a single protein or even in different proteins) seems to be a more difficult task. Nevertheless, this approach may become a promising alternative for development of a live attenuated marker vaccine against PRRS [8].

Table 4 provides main characteristics of some candidate vaccines against PRRS, developed on various biotechnological platforms.

Thus, at the current stage of PRRS pathogenesis study, three major challenges in developing more efficient next-generation vaccines can be identified: insufficient understanding of immune protection mechanisms, the virus’s ability to induce negative regulatory signals for the immune system and its substantial antigenic variability [59]. In particular, the last factor is the reason behind poor efficacy of the existing vaccines against heterologous infection. Further in-depth analysis of the host’s immune response, as well as the identification of T- and B-cell epitopes in PRRSV structure, will ensure rational design of genetically engineered vaccines and ultimately attaining the optimal safety-efficacy profile.