The changing disguises PRRSV might use to hide from a pig's immunity

Glycosylation pattern of a PRRSV sequence could be a relevant aspect to understanding the turnover of different PRRSV strains in the field.

December 20, 2022

4 Min Read
The changing disguises PRRSV might use to hide from a pig's immunity
National Pork Board

Poor cross-protection between different strains of porcine reproductive and respiratory syndrome virus is one of the foremost challenges producers face when immunizing pigs to prevent and manage PRRSV outbreaks. Despite performing better than their unvaccinated counterparts, vaccinated animals still get infected and may show clinical signs in a PRRSV outbreak, depending largely on the strain that infects them.

Experimental studies show that changes in the virus's genetic sequence that result in the gain or loss of protein N-glycosylation sites have the potential to influence the virus's ability to evade the pig's immune system. However, the potential role of such genetic changes in driving the emergence of new PRRSV strains in the field is not known.

Protein N-glycosylation is a post-translational process that involves the addition of sugars to particular viral protein regions. These modifications can alter how these viral proteins are identified by the host. Animals infected with different PRRSV strains that had varied glycosylation patterns showed varying neutralizing antibody production profiles, which suggests that the presence or lack of specific glycosylation could change the virus's immunogenicity.

The genetic diversity of PRRSV-2 includes a large number of lineages and sub-lineages, and it is believed that immunologic pressure is largely responsible for the evolution of various strains of PRRSV-2. As yet, it is unknown whether different PRRSV-2 lineages exhibit distinct glycosylation patterns, an observation that would support the hypothesis that lineages are immunogenically distinct.

To explore the occurrence of different glycosylation patterns of PRRSV in the U.S. over time, we analyzed almost 20,000 PRRSV ORF5 sequences from the University of Minnesota Veterinary Diagnostic Laboratory from 2004 to 2021. The ORF5 gene encodes the GP5 protein, which contains the Principle Neutralizing epitope for PRRSV. To visualize phylogenetic relationships, we constructed a time-scaled phylogenetic tree for 500 randomly selected sequences (see Figure).

We identified nine sites that are potentially glycosylated on the GP5 protein. Those are sites 30, 32, 33, 34, 35, 44, 51, 57 and 59. Different combinations of glycosylated sites were prevalent over time. Even though the glycosylation patterns found in different lineages were not necessarily lineage-defining, the emergence of certain combinations of glycosylations coincided with past PRRSV epidemics in the United States. For example, the rapid expansion of sub-lineages L1A, L1C, and L1H were associated with a novel glycosylation pattern that emerged in those sublineages. For L1A, sequences glycosylated at sites 32, 33, 44, 51 and 57 first appeared in 2012, and by 2014 it represented more than 40% of all L1A sequences identified and reached a peak of 62% of all L1A sequences identified in 2015. This coincides with the emergence of the L1A 1-7-4 virus, which was and still is a widely recognized event of clinical significance in the industry.

UMN Fig 1 122022.JPG

The emergence of the L1C 1-4-4 variant in 2020 can also be observed from a glycosylation pattern perspective. This virus's glycosylation pattern (at sites 32, 33, 44 and 51) was circulating since at least 2007, though represented only a small percentage of sequences. In 2020 and 2021, this pattern was observed in 44 and 47% of the L1C sequences identified in those years. Glycosylation patterns are not solely responsible for the emergence of new strains. However, in a dynamic landscape of cross-immunity elicited by diverse immunization practices and natural occurrence of PRRSV, we hypothesize that the relative fitness of viruses with specific glycosylation patterns may change over time.

As an observational study, we cannot assess causality (do novel glycosylation patterns drive viral fitness for a given strain, or are these mutations just coincidental hitchhikers present in a successful strain?). However, studies have shown that the glycosylation of proteins is relevant to protein folding, immune recognition, neutralization and immune evasion of viruses, all of which support the hypothesis that the glycosylation pattern of a PRRSV sequence could be a relevant aspect when it comes to understanding the turnover of different PRRSV strains in the field. Further studies are needed to explore how that can be leveraged to improve PRRSV control.

This work was supported by the USDA National Institute of Food and Agriculture, by the joint NIFA-NSF-NIH-BBSRC Ecology and Evolution of Infectious Disease award 2019-67015-29918 and BB/T004401/1 and by the USDA NIFA Critical Agricultural Research and Extension program 2022-68008-37146. The entire publication is available here.

Source: Igor Paploski, Dennis Makau, Nakarin Pamornchainavakul, Julia P. Baker, Albert Rovira, Kimberly VanderWaal and Declan Schroeder, who are solely responsible for the information provided, and wholly owns the information. Informa Business Media and all its subsidiaries are not responsible for any of the content contained in this information asset.

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