PPRS anti-viral treatment could be coming

By Carl A. Gagnon

Editor’s note: Carl A. Gagnon is a veterinary scientist at the University of Montreal’s Swine and Poultry Infectious Diseases Research Centre. He can be contacted at carl.a.gagnon@umontreal.ca.

PRRS is estimated to cost the U.S. industry nearly USD $700 million (CAD $950 million) annually. Combining various jurisdictions in Europe, the total reaches more than €1.5 billion (CAD $2 billion) each year. Recommendations for preventing the spread of PRRS are identified in several parts of the Canadian Pork Excellence (CPE) program manual’s section on biosecurity.

Porcine Reproductive and Respiratory Syndrome (PRRS) results in reproductive failure, late-term abortions, an increased number of stillborn fetuses or the birth of premature and weak piglets. This global phenomenon also leads to increased morbidity and mortality in growing and finishing pigs as a result of severe respiratory disease and poor growth performance.

As PRRS continues to take a large toll on the swine industry in terms of animal health and lost revenue, an effective anti-viral treatment for the disease has remained elusive. One potential solution to this problem includes the use of a substance derived from Actinobacillus pleuropneumoniae (“App”) – a pathogen responsible for about 20 per cent of bacterial pneumonia in pigs, causing inflammation of the lungs and, potentially, death.

In this particular case, perhaps surprisingly, the pathogen is beneficial. By studying the co-infection of PRRS virus and App, which occurs naturally in pigs, it has been demonstrated that heat-resistant App-secreted metabolites have a positive anti-viral effect against the PRRS virus, but, until recently, the specific metabolites responsible were unknown.

As such, it has become necessary to find out which App metabolites are behind this anti-viral effect, to further isolate and test them. If it is possible to isolate and test those metabolites, it may offer a potential solution for combatting PRRS virus at the cellular level.

Taking a closer look at App metabolites

Immunofluorescence comparing a PRRS virus sample to a sample of PRRS virus mixed with App shows that the latter has a significant anti-viral effect versus the control ‘mock’ sample (with no infected cells).

Targeted mass spectrometry has made it possible to take a closer look at how a certain PRRS-infected porcine cell line reacts when exposed to App. By using untargeted spectrometry, it is possible to examine a wider spread of potential culprits.

After analyzing mass spectrometry data, various App metabolites stood out. All of the top-five App-secreted metabolites were adenosine nucleoside analogs – a class of metabolites widely known to have anti-viral properties. Fortunately, many adenosine nucleotide-based drugs are commonly available to treat other human viruses, with extensive research promoting their use.

The identified metabolites were further analyzed to better understand the concentration at which they are most effective in response to PRRS virus infection. Three of the five metabolites subject to analysis proved efficient in reducing the growth of PRRS virus in cell culture, which is good news, at least in a lab setting.

Existing drugs could act as PRRS anti-virals

Adenosine nucleotide analog anti-viral drugs act against certain human viruses – including strains of Hepatitis and HIV – to limit their growth. These drugs function similar to how App affects PRRS, though the relationship warrants further investigation.

For application at the farm level, it is uncertain how practical it would be, at this time, to begin employing such anti-virals against PPRS, given the required concentration of metabolites. However, confidence remains, given the commercial availability of those comparable anti-viral drugs, providing hope that a PRRS anti-viral may be on its way before long.