title: Enhancement of innate immunity with granulocyte colony-stimulating factor did not mitigate disease in pigs infected with a highly pathogenic Chinese PRRSV strain.
abstract: Porcine reproductive and respiratory syndrome virus (PRRSV) is responsible for one of the most economically important diseases in swine worldwide. It causes reproductive failure in sows and pneumonia in pigs that predisposes them to secondary bacterial infections. Methods to control PRRSV and/or limit secondary bacterial infections are desired to reduce the impact of this virus on animal health. Neutrophils play a major role in combatting infection; they can act as phagocytes as well as produce and release lytic enzymes that have potent antimicrobial effects leading to the destruction and clearance of bacterial pathogens. Granulocyte-colony stimulating factor (G-CSF) is a cytokine that controls the production, differentiation and function of granulocytes (including neutrophils) from the bone marrow. Recent work from our laboratory has shown that encoding porcine G-CSF in a replication-defective adenovirus (Ad5-G-CSF) and delivering a single dose to pigs induced a neutrophilia lasting more than two weeks. As secondary bacterial infection is a common occurrence following PRRSV infection, particularly following challenge with highly pathogenic (HP)-PRRSV, the aim of the current study was to evaluate the effectiveness of a single prophylactic dose of adenovirus-encoded G-CSF to mitigate secondary bacterial disease associated with HP-PRRSV infection. Administration of Ad5-G-CSF induced a significant neutrophilia as expected. However, between 1 and 2days following HP-PRRSV challenge the number of circulating neutrophils decreased dramatically in the HP-PRRSV infected group, but not the non-infected Ad5-G-CSF group. Ad5-G-CSF administration induced monocytosis as well, which was also reduced by HP-PRRSV challenge. There was no difference in the progression of disease between the Ad5-G-CSF and Ad5-empty groups following HP-PRRSV challenge, with pneumonia and systemic bacterial infection occurring in both treatment groups. Given the impact of HP-PRRSV infection on the neutrophilia induced by the Ad5-G-CSF administration, additional studies are warranted to evaluate the timing of Ad5-G-CSF induced neutrophilia and multiple G-CSF inoculations on protection against secondary bacterial infection following PRRSV infection. Nevertheless, this study may provide insight into the pathogenesis of HP-PRRSV.
authors: Virus and Prion Research Unit, National Animal Disease Center, USDA, Agricultural Research Service, Ames, IA, United States.
authors: Sarah N
authors: SN
authors: Schlink
authors: Virus and Prion Research Unit, National Animal Disease Center, USDA, Agricultural Research Service, Ames, IA, United States. Electronic address: kelly.lager@ars.usda.gov.
authors: Kelly M
authors: KM
authors: Lager
authors: Virus and Prion Research Unit, National Animal Disease Center, USDA, Agricultural Research Service, Ames, IA, United States.
authors: Susan L
authors: SL
authors: Brockmeier
authors: Virus and Prion Research Unit, National Animal Disease Center, USDA, Agricultural Research Service, Ames, IA, United States.
authors: Crystal L
authors: CL
authors: Loving
authors: Virus and Prion Research Unit, National Animal Disease Center, USDA, Agricultural Research Service, Ames, IA, United States.
authors: Laura C
authors: LC
authors: Miller
authors: Virus and Prion Research Unit, National Animal Disease Center, USDA, Agricultural Research Service, Ames, IA, United States.
authors: Ann C
authors: AC
authors: Vorwald
authors: China Agricultural University, Beijing, China.
authors: Han-Chun
authors: HC
authors: Yang
authors: Virus and Prion Research Unit, National Animal Disease Center, USDA, Agricultural Research Service, Ames, IA, United States.
authors: Marcus E
authors: ME
authors: Kehrli
authors: Virus and Prion Research Unit, National Animal Disease Center, USDA, Agricultural Research Service, Ames, IA, United States.
authors: Kay S
authors: KS
authors: Faaberg
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics*; D007113:Immunity, Innate / Q000187:drug effects; D019318:Porcine Reproductive and Respiratory Syndrome / Q000276:immunology* / Q000382:microbiology / Q000473:pathology / Q000821:virology; D013552:Swine
chemical_list: D016179:Granulocyte Colony-Stimulating Factor
keywords: G-CSF; HP-PRRSV; Neutrophils; Swine