title: Reduction of porcine reproductive and respiratory syndrome virus (PRRSV) infection in swine alveolar macrophages by porcine circovirus 2 (PCV2)-induced interferon-alpha.
abstract: Two common viral pathogens of swine, namely, porcine circovirus type 2 (PCV2) and porcine reproductive and respiratory syndrome virus (PRRSV), were investigated in regard to their effects on monolayer cultures of swine alveolar macrophages (AMs). The purpose was to identify selected cellular changes and responses potentially associated with the clinical reactions of pigs infected with either or both of these viruses. Measurements included the (1) absolute and relative numbers of infected, viable, and apoptotic cells; (2) distribution of viral antigens; (3) levels of interferon-alpha (IFN-alpha) and tumor necrosis factor-alpha (TNF-alpha) produced and their association with the extent of virus-induced cytopathology. Four groups of AMs were studied, including mock-infected, PCV2 alone-infected (PCV2-A), PRRSV alone-infected (PRRSV-A), and PCV2 and PRRSV dually infected (PCV2/PRRSV) groups. The AMs of PCV2-A group had high antigen-containing rate without cell death. There was a marked increase in cell death and apoptosis in PRRSV-A group. However, a lower PRRSV-induced infectious rate, cell death, and apoptosis were seen in PCV2/PRRSV group. High levels of IFN-alpha production were detected in PCV2-infected groups, but not in mock-infected and PRRSV-A groups. The PRRSV-induced cytopathic effect (CPE) on MARC-145 cells or swine AMs was markedly reduced by pre-incubation of the cells with UV-treated or non-UV-treated supernatants of PCV2-infected AMs. In addition, the reduction in CPE was abolished when the supernatants of PCV2-infected AMs were pre-treated with a mouse anti-recombinant porcine IFN-alpha antibody. The results suggest that swine AMs were an important reservoir of PCV2; PCV2 infection reduced PRRSV infection and PRRSV-associated CPE in PCV2/PRRSV AMs; the reduction of PRRSV infection in AMs was mediated by IFN-alpha generated by PCV2 infection. The reduced PRRSV-associated CPE in AMs and increased pro-inflammatory cytokine production may lead to a more severe pneumonic lesion in those dually infected pigs.
authors.affiliation: Graduate Institute of Veterinary Medicine, National Taiwan University, Taipei 106, Taiwan, ROC.
authors.forename: Hui-Wen
authors.initials: HW
authors.lastname: Chang
authors.forename: Chian-Ren
authors.initials: CR
authors.lastname: Jeng
authors.forename: Jiuan J
authors.initials: JJ
authors.lastname: Liu
authors.forename: Tsang-Long
authors.initials: TL
authors.lastname: Lin
authors.forename: Chih-Cheng
authors.initials: CC
authors.lastname: Chang
authors.forename: Mi-Yuan
authors.initials: MY
authors.lastname: Chia
authors.forename: Yi-Chieh
authors.initials: YC
authors.lastname: Tsai
authors.forename: Victor F
authors.initials: VF
authors.lastname: Pang
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D000956:Antigens, Viral / Q000032:analysis; D017209:Apoptosis / Q000276:immunology; D001681:Biological Assay / Q000662:veterinary; D018173:Circoviridae Infections / Q000150:complications / Q000276:immunology* / Q000821:virology; D017925:Circovirus / Q000276:immunology*; D003588:Cytopathogenic Effect, Viral / Q000276:immunology; D005260:Female; D005455:Fluorescent Antibody Technique / Q000662:veterinary; D016898:Interferon-alpha / Q000096:biosynthesis / Q000276:immunology*; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000821:virology; D008297:Male; D019318:Porcine Reproductive and Respiratory Syndrome / Q000276:immunology* / Q000821:virology; D019316:Porcine respiratory and reproductive syndrome virus / Q000276:immunology*; D013047:Specific Pathogen-Free Organisms; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D016898:Interferon-alpha; D014409:Tumor Necrosis Factor-alpha