Infectious bursal disease virus: strains that differ in virulence differentially modulate the innate immune response to infection in the chicken bursa.
Little is understood about the immune responses involved in the pathogenesis of infectious bursal disease virus (IBDV). Strains of IBDV differ in their virulence: F52/70 is a classical virulent strain (vIBDV), whereas UK661 is a very virulent strain (vvIBDV) that causes greater pathology and earlier mortality. The exact causes of clinical disease and death are still unclear. Pro-inflammatory cytokines such as interleukin (IL)-1beta and IL-6, produced by activated macrophages, could play a role, as could cytokines produced by T and natural killer (NK) cells, such as interferon (IFN)-gamma, which stimulate macrophages. We quantified mRNA transcription in bursal tissue, by real-time quantitative reverse transcription- polymerase chain reaction (RT-PCR), for the type I IFN (IFN-alpha and IFN-beta), pro-inflammatory cytokines (IL-1beta, IL-6, and CXCLi2), the anti-inflammatory cytokine transforming growth factor (TGF)-beta4, and Th1 cytokines (IFN-gamma, IL-2 [and the closely related IL-15], IL-12, and IL-18) for the first 5 days after infection of 3-week-old chickens with F52/70 or UK661 and compared these with levels in bursal tissue from uninfected age-matched controls. Both strains induced a pro-inflammatory response, evidenced by increased mRNA transcription of IL-1beta, IL-6, and CXCLi2, and down-regulation of TGF-beta4, of similar magnitude and timing. IFN-gamma mRNA was induced by both strains, although to a greater degree by the vvIBDV strain, indicating that a cell-mediated response is induced. Neither virus initially induced high levels of type I IFN. F52/70 seems to use a "stealth" approach by not inducing the type I IFNs, whereas UK661 down-regulates their expression. This suggests that both viruses modulate the host immune response, although probably by using different mechanisms.
Institute for Animal Health, Compton, Berkshire, United Kingdom.
Ibrahim
I
Eldaghayes
Lisa
L
Rothwell
Andrew
A
Williams
David
D
Withers
Sucharitha
S
Balu
Fred
F
Davison
Pete
P
Kaiser
D000818:Animals; D018175:Birnaviridae Infections / Q000276:immunology / Q000662:veterinary* / Q000821:virology; D002060:Bursa of Fabricius / Q000276:immunology / Q000821:virology*; D002645:Chickens / Q000276:immunology / Q000821:virology; D016207:Cytokines / Q000378:metabolism; D005786:Gene Expression Regulation; D007113:Immunity, Innate / Q000276:immunology*; D007243:Infectious bursal disease virus / Q000276:immunology* / Q000472:pathogenicity*; D007249:Inflammation / Q000378:metabolism; D011201:Poultry Diseases / Q000276:immunology* / Q000821:virology*; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D019562:Viral Load; D014774:Virulence
D016207:Cytokines; D012333:RNA, Messenger