Genetic diversity of the PRRS virus in swine: causes and consequences

One hallmark of the PRRS virus in swine is its extremely high genetic diversity. This phenomenon has important implications for disease diagnosis and prevention and is one of the major causes of the partial or complete lack of protection against re-infections.
The PRRS virus is an RNA virus that belongs to the genus Arterivirus, the only genus in the family Arteriviridae, in the order Nidovirales. The PRRS virus contains a non-segmented, single-stranded, positive-sense RNA genome. The RNA genome is composed of ten open reading frames (ORFs).
Since the first outbreaks of PRRS in swine in America and Europe, two PRRS virus genotypes have been designated: European or Type 1 (prototype Lelystad virus) and North-American or Type 2 (prototype VR-2332). Interestingly, similarity between both prototype nucleotide sequences is as low as 55%. More importantly, intratype pairwise nucleotide sequence variation exceeds 20% (up to 30% in type 1 and around 21% in type 2).
A significant number of subtypes has been identified in both genotypes. Within type 1, there are at least 4 different subtypes; subtype I is predominant in Western Europe, whereas subtypes II-IV are isolated only in countries to the East of Poland. It seems that genetic variability within subtypes II-IV is higher than within subtype I (18.2% vs. 11.9% using ORF5, respectively). Regarding type 2, although subtypes have not been clearly defined, several lineages exist in two well-defined clades; seven lineages made up by North-American isolates and two lineages exclusively consisting of isolates from South-East Asia.

  

It has been described that the allocation of genetic diversity is not constant along the PRRS virus genome. Thus, it seems that diversity occurs more frequently in ORF1a, ORF3 and ORF4. However, it is important to note that phylogenetic analyses to determine subtypes and lineages have generally been based on ORF5, which represents a low percentage of the total viral genome. We cannot rule out that this classification may change in the future using the whole genome.
There are several causes that may explain why the PRRS virus in swine has such a highly genetic diversity:

  
Random mutations. As an RNA virus, the PRRS virus has an RNA polymerase that does not have the ability to correct the inherent common errors that occur during the transcription of RNA. Since these errors appear every 100-1,000 nucleotides, each new virus may be different to the previous one. The PRRS virus mutation rate is assumed to be the highest so far for a virus, being up to 40 times higher than the mutation rates of well-known viruses, such as the avian influenza virus or human immunodeficiency virus.
Recombination. Recombination among PRRS virus strains has frequently been demonstrated in both genotypes, indicating that this phenomenon is also very important in PRRS virus genetic diversity.
Immune selection. During infection, predominant variants would be those variants that possess changes in their genome which represent an advantage compared to the parental strain, such as the ability to escape from the immune response. Therefore, as PRRS virus variants are constantly created, producing new forms of antigens, host immune responses could cause selection pressure.
There are several consequences of such genetic diversity, all them implying a complication in diagnosis (false negatives in ELISA and PCR assays) and control (appearance of new highly pathogenic strains and immune escape mutants) of the PRRS disease in swine.

New video tutorial on BIOSECURITY: one of the key points for the control of PRRS in pigs

A PRRS control program cannot be conceived without implementing biosecurity measures. Whilst external biosecurity focuses on exclusion (not allowing it to enter) internal biosecurity focuses on containment (not allowing it to move).
The biggest problem today for the control of PRRS in pigs is that immunity induced against the strain circulating within the farm (called homologous immunity) will never confer 100% cross-protection against the arrival of a new strain (called heterologous strain). Understanding how good or bad the external biosecurity measures are is essential to be able to predict how high the risk of suffering the arrival of new strains is, but also very helpful in deciding the vaccine program strategy to be used.

Watch the video

  
The 3 main routes for new PRRS virus strains to break into farms are transport vehicles, live animals and airborne transmission. The risk of heterologous infections can be minimized by controlling these 3 main routes of transmission, but other routes of infection should also be taken into account such as semen, personnel, fomites and insects.
Once infection occurs, the virus will be shed from infected animals via blood, saliva, milk, colostrum, urine, faeces and semen. Moreover, some pigs have been reported to have been persistently infected for at least 200 days. Therefore, internal biosecurity refers to any type of measures implemented which manage to help to reduce the spread of the PRRS virus within the animals. These measures will be mainly related to management protocols and hygiene. The main factors to be considered when evaluating the internal biosecurity measures are the pig flow, personnel equipment, needles, fomites and insects. Obviously, personnel compliance is the key to successful implementation of such procedures for the control of PRRS in pigs.
Veterinarians can play an important role, not only as the team members who deliver science-based biosecurity to the farm, but also as teachers to educate personnel and auditors to ensure that compliance is maximized.

Combined administration of PRRS vaccine with PPV and SE vaccine effectively controls PRRSV viraemia

The combined administration of a live PRRS vaccine (UNISTRAIN® PRRS) and a PPV and SE vaccine (ERYSENG® PARVO) reduces viraemia and vertical/horizontal transmission following a heterologous PRRSV challenge.
The combination of two immunological veterinary medicinal products manufactured by HIPRA -UNISTRAIN® PRRS and ERYSENG® PARVO- has successfully been registered in Europe. When combining a live PRRS vaccine with a PPV and SE vaccine, the most important marker of effective protection is demonstration that the PRRS vaccine remains alive and active in combination. Unlike other companies, HIPRA has proven the viability of the PRRS vaccine in combined use with UNISTRAIN® PRRS and ERYSENG® PARVO and, in so doing, it has demonstrated the efficacy of this combination against PRRSv, SE and PPV:
A major concern in PRRS management is the ability of a given vaccine to control viraemia. The study described below demonstrates that gilts vaccinated with the combination of UNISTRAIN® PRRS and ERYSENG® PARVO results in better control over viraemia versus non-vaccinated gilts after a heterologous challenge.
The animals used in this trial were clinically healthy six-month-old gilts free from antibodies against PPV, E. rhusiopathiae and PRRSV. The animals were divided into two groups: a vaccinated group and a control group. The animals in the former group were vaccinated seven weeks before mating with ERYSENG® PARVO (2 ml/dose) and revaccinated four weeks before mating with the combination of UNISTRAIN® PRRS and ERYSENG® PARVO (2 ml/dose). The control group remained unvaccinated. All gilts were challenged with a heterologous pathogenic PRRSV strain at 90 days of gestation, as this is the time when gestating sows are most sensitive to PRRSV. All the animals were sampled before challenge, after challenge and after birth to assess the progression of viraemia and the vertical/horizontal transmission to piglets by RT-PCR.

Visit prrscontrol here
The results obtained showed that all gilts were negative for viruses after vaccination. After challenge, viraemia was observed in all non-vaccinated animals (100%), while in the vaccinated group, two gilts were positive in two independent samples. The length of the viraemic period was significantly shorter in the vaccinated group (2.5 days) than in the control group (16.9 days).
  
Vertical transmission of PRRSV to piglets was significantly inhibited in the vaccinated group (6.3% of piglets tested positive for PRRSV at birth) in comparison with the control group (65.9%). Horizontal transmission between piglets during the lactation period was lower in the vaccinated group, as all vaccinated piglets were free of PRRSV when weaned, while 51.5% of piglets in the control group tested positive for PRRSV when weaned.

  

Vaccination with the combination of UNISTRAIN® PRRS and ERYSENG® PARVO significantly reduced the length of viraemia and vertical/horizontal transmission to piglets after field infection. Therefore, the combination has been proven to reduce PRRSV infection pressure on farms and help stabilise farms faster.