Influenza and PRRSV: Similarities, differences, and interactions

PRRSV and influenza virus belong to different families with different pathogenicity mechanisms, but both viruses share some characteristics:

• High genetic diversity: Both viruses have a very high mutation rate and, although they do so by different mechanisms, they both have the ability to exchange parts or segments of their genome.
• High diffusion: >70% of Spanish farms are positive for both.
• Ability to establish themselves endemically on farms:
  • IAV: The endemic form is established by the presence of subpopulations with different levels of immunity on the farm. The difference in immune “experience” in younger and older sows can impact the occurrence of infection in farrowing rooms, where piglets born to young sows are more likely to become infected. This early transmission usually occurs horizontally, between litters, or even via fomites. Seroconversion has been described in sows during the lactation phase, which would indicate that piglets can be a source of infection to sows. Most commonly, piglets become infected in the nursery as maternal antibodies decline. In affected nurseries, an increased incidence of IAV is usually observed, associated with increased clinical parameters (sneezing, coughing, and severe coughing).
  • PRRS: Vertical transmission is common, and piglets being born viraemic are key to maintaining the infection cycle on the farm. The greater the number of piglets born viraemic, the greater the horizontal transmission during the nursery phase.

In their endemic forms, both viruses have similar R₀ transmission values on average (between 2 and 7) but different durations of infectiousness.

• For PRRSV it is much longer (>3 weeks in piglets).
• For IAV it is shorter (5-7 days on average), so transmission occurs more quickly. Even in endemic situations, epidemic transmissions can be observed, reaching more than 10 infections from a single seed animal in certain pens or batches, something hardly observed with PRRSV in endemic situations.

Interaction with other pathogens: different modes of action

Another common aspect is the increase in secondary bacterial infections. Again, the reasons are not the same:

• IAV: The virus causes destruction of the ciliated epithelium and very intense inflammation in the respiratory tract. This facilitates colonization by bacterial pathogens that can reach the lung, increasing the frequency of secondary bacterial pneumonia.

Clear synergies have been described between IAV and Mycoplasma hyopneumoniae and with Actinobacillus pleuropneumoniae.

• PRRSV (conventional strains): Infection is limited to permissive macrophages, which are scarce in the upper and middle airways and primarily found in the alveoli and pulmonary vessels. Inflammation may be significant in the lung but does not manifest significantly in other tissues. The clinical manifestations associated with primary PRRSV infection are variable at the respiratory level, which does not mean they cannot be significant. Depending on the virulence of each strain, the infection is associated with a worsening of the immune response as well as a depletion of alveolar macrophages. This facilitates the entry of other bacteria, increasing the rate of pneumonia and systemic bacterial infections. Synergies between PRRSV and PCV2 have also been described.
• PRRS (high virulence strains): Inflammation is much more notorious and causes a primary respiratory pathology with very clear clinical signs associated with mortality from the beginning. If they survive the infection, the animals are clearly predisposed to suffer bacterial infections for long periods, since this infection is associated with atrophy of the thymus and very marked lymphopenia.

Interaction between swine IAV and PRRSV

The interaction between these two viruses is complex, and conflicting results are not uncommon. In an experimental study, Van Reeth et al. examined co-infection by PRRSV and IAV in two groups of animals. While in one group a clear synergy between the two viruses was observed, in the other group a milder clinical picture than expected for each of the viruses separately was observed.

In a more recent study (Martín-Valls et al., 2022), the presence of eleven respiratory viruses, including IAV, PRRSV1, PCV2, porcine cytomegalovirus (PCMV), porcine respiratory coronavirus (PRCV) and swine orthopneumovirus (SOV), was evaluated at the individual and farm level. Results at the farm level showed association between IAV, PCMV, and SOV, but not with PRRS virus. At the individual level, IAV and PRRS virus correlated negatively. This negative correlation had also been described in vitro in a study in which replication interference was observed in co-infected CD163+ epithelial cells. In another experimental in vivo study, previous PRRSV infection negatively interfered with IAV infection.

However, in a recent study where the simultaneous circulation of these two viruses was evaluated in pig populations followed longitudinally between birth and the end of the weaning phase, it was observed that the presence of a highly virulent PRRS virus resulted in:

• an increase in the number of animals repeatedly infected with IAV,

• an increase in the duration of IAV infection (in some cases over 2 weeks). This could be associated with a worsening of the immune response of these animals.

It is very difficult to assess the impact on production and health. Cornelison et al. compared two farms co-infected with PRRSV and IAV with a farm infected only with PRRSV and observed an increase of up to 19% in mortality in the co-infected farms, and a reduction in average daily gain (cumulative to slaughter age) of between 8 and 14%.

Conclusion

The relationship between these viruses is complex and can be contradictory between studies. The emergence of highly pathogenic strains of PRRSV and the high genetic diversity of both viruses makes it very difficult (if not impossible) to predict the relative impact of each virus. Although they apparently do not add up at the individual level, their impact both separately and in combination at the farm level is very clear.