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.


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