1a.Objectives (from AD-416):
Examine the pathogenesis of secondary bacterial infections subsequent to porcine reproductive and respiratory syndrome virus (PRRSV) infection and evaluate intervention strategies to prevent or treat such infections.
1b.Approach (from AD-416):
In 2006, large outbreaks of a high morbidity/high mortality disease that became known as "porcine high fever disease" (PHFD) began to occur across China, and in 2007, Vietnam began to experience swine disease outbreaks causing clinically similar signs. The disease is associated with newly-emergent, highly-pathogenic porcine reproductive and respiratory syndrome virus (PRRSV) strains, but in both of these outbreaks other viruses and bacteria were often isolated from clinical cases. Results suggest that the cause of the swine deaths in PHFD is a multifactorial syndrome with PRRSV as a major factor. We will compare 2 Asian isolates of PRRSV obtained from the PHFD outbreaks to high and low virulence isolates of PRRSV obtained from the United States for their alteration of innate immune functions and their ability to predispose to secondary bacterial infections in swine. Subsequently, we will compare several antibiotic regimens for their ability to treat or prevent severe bacterial disease that occurs as a sequela to PRRSV infection.
The animal experiment described for year 1 has been completed and extensive laboratory analyses of samples are underway. Pigs were infected with one of four isolates of porcine reproductive and respiratory syndrome virus (PRRSV), two U.S. isolates - one of lower pathogenicity (VR2332) and one of moderate pathogenicity (SDSU73), and 2 Asian strains - a Chinese isolate (JXwn06) and a Vietnamese isolate (SRV07), both from cases of porcine high fever disease and/or a cocktail of the bacteria Streptococcus suis, Haemophilus parasuis, and Actinobacillus suis. The purpose of the experiment was to delineate differences between Asian and U.S. isolates with regard to the severity of disease and alterations in the host innate immune response in pigs; determine if Asian and U.S. isolates equally predispose to secondary bacterial infections; determine the contribution of secondary bacterial infection to the morbidity/mortality associated with PHFD; and determine the mechanisms by which PRRSV predisposes to secondary infection. We have evaluated severity of disease and confirmed that these four isolates represent a spectrum of pathogenicity with the Chinese isolate (JXwn06) being the most pathogenic, the U.S. isolate VR2332 being the least pathogenic, and the Vietnamese (SRV07) and U.S. SDSU73 isolates falling in between. Viremia generally correlates with the pathogenicity of the virus with highest levels seen with the Chinese (JXwn06) strain. A pig coinfected with JXwn06 and bacteria displayed neurologic signs and had to be euthanized, but this was the only pig to succumb to disease during the experiment. Bacteria (A. suis and/or H. parasuis) were isolated from more pigs challenged with the Asian PRRSV strains than with the U.S. PRRSV strains or with bacteria alone and these bacteria were not isolated from any of the non-challenged control pigs or any of the pigs challenged with virus alone. We are in the process of determining and analyzing immune data to determine alterations in the immune response caused by the various strains.