title: Synergistic effects of sequential infection with highly pathogenic porcine reproductive and respiratory syndrome virus and porcine circovirus type 2.
abstract: BACKGROUND
  Porcine reproductive and respiratory syndrome virus (PRRSV) is the causative agent of porcine reproductive and respiratory syndrome (PRRS) and porcine circovirus type 2 (PCV2) is associated with postweaning multisystemic wasting syndrome (PMWS) in pigs. Coinfection with highly pathogenic PRRSV (HP-PRRSV) and PCV2 in the field has recently become extensive in some Asian countries. A synergistic pathogenicity between PRRSV and PCV2 infections has previously been reported. However, the consequences of the sequential infection of pigs with these two viruses are unknown.
  
  
  METHODS
  Thirty 35-day-old piglets were randomly divided into six groups (n = 5 each): HP-PRRSV/PCV2 (group 1, inoculated with HP-PRRSV, then inoculated with PCV2 one week later), PCV2/HP-PRRSV (group 2, inoculated with PCV2, then inoculated with HP-PRRSV one week later), HP-PRRSV+PCV2 (group 3, inoculated with HP-PRRSV and PCV2 concurrently), HP-PRRSV (group 4, inoculated with HP-PRRSV), PCV2 (group 5, inoculated with PCV2), and the control (group 6, uninfected). This experiment lasted 28 days. Clinical symptoms and rectal temperatures were recorded each day after inoculation, body weight was recorded weekly, and serum samples were obtained for viral nucleic acid quantification and antibody titration. Variations in CD3+, CD4+ CD8-, CD3+, CD4-, and CD8+ cells, natural killer (NK) cells, and mononuclear cells were determined by flow cytometry. The serum concentrations of interferon γ (IFN-γ), tumor necrosis factor α (TNF-α), interleukin 10 (IL-10), and macrophage granulocyte-colony stimulating factor (GM-CSF) were determined. Pathological changes in different tissues from the experimentally infected pigs were recorded.
  
  
  RESULTS
  The piglets in group 1 had the highest viral loads, the lowest antibody titers, the most-severe clinical signs, and the highest mortality (3/5, 60%; the mortality in the other groups was 0%), and interstitial pneumonia was more severe in this group compare to the other HP-PRRSV infected groups. The serum levels of IFN-γ, TNF-α, IL-10, and GM-CSF varied (increased or decreased) most widely in group 1, as did each immunocyte subgroup.
  
  
  CONCLUSIONS
  HP-PRRSV infection followed by PCV2 infection enhanced the replication of both viruses in the experimental piglets and led to more-severe clinical signs and lesions, indicating greater synergistic effects during the sequential infection of piglets with HP-PRRSV and then PCV2.
authors: Division of Swine Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, 427 Maduan Street, Nangang District, Harbin 150001, China. lcm@hvri.ac.cn.
authors: Peihu
authors: P
authors: Fan
authors: Yanwu
authors: Y
authors: Wei
authors: Longjun
authors: L
authors: Guo
authors: Hongli
authors: H
authors: Wu
authors: Liping
authors: L
authors: Huang
authors: Jianbo
authors: J
authors: Liu
authors: Changming
authors: C
authors: Liu
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D018173:Circoviridae Infections / Q000473:pathology / Q000662:veterinary* / Q000821:virology; D017925:Circovirus / Q000502:physiology*; D016207:Cytokines / Q000097:blood; D005434:Flow Cytometry; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008962:Models, Theoretical; D019318:Porcine Reproductive and Respiratory Syndrome / Q000473:pathology* / Q000821:virology*; D019316:Porcine respiratory and reproductive syndrome virus / Q000502:physiology*; D016019:Survival Analysis; D013552:Swine; D013553:Swine Diseases / Q000473:pathology* / Q000821:virology*; D019562:Viral Load
chemical_list: D000914:Antibodies, Viral; D016207:Cytokines
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