Activation of PI 3-kinase/Akt/NF-kappaB and Stat3 signaling by avian reovirus S1133 in the early stages of infection results in an inflammatory response and delayed apoptosis.
Avian reovirus (ARV) strain S1133 causes apoptosis in host cells in the middle to late stages of infection. This study investigated the early-stage biological response and intracellular signaling in ARV S1133-infected Vero and chicken cells. Treatment with conditioned medium from ARV S1133-infected cells increased the chemotactic activity of U937 cells. Neutralizing antibodies against IL-1beta and IL-6 showed that both cytokines contribute to viral-induced inflammation but neither affect cell survival. Inhibition of Akt, NF-kappaB, and Stat3 released the chemotactic activity and anti-apoptotic effect elicited by ARV S1133. ARV S1133 activated PI 3-kinase-dependent Akt/NF-kappaB and p70 S6 kinase, as well as Stat3; however, p70 S6 kinase was not involved in ARV S1133-mediated effects. DF1 cells over-expressing constitutively active PI 3-kinase and Stat3 showed association with enhancement of anti-apoptotic activity. In conclusion, in the early stages of ARV S1133 infection, activation of cell survival signals contributes to virus-induced inflammation and anti-apoptotic response.
Lin
Ping-Yuan
PY
Graduate Institute and Department of Life Science, Tzu-Chi University, Hualien, Taiwan.
Liu
Hung-Jen
HJ
Liao
Ming-Huei
MH
Chang
Ching-Dong
CD
Chang
Chi-I
CI
Cheng
Hsueh-Ling
HL
Lee
Jeng-Woei
JW
Shih
Wen-Ling
WL
D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D002642:Chick Embryo; D002522:Chlorocebus aethiops; D054884:Host-Pathogen Interactions; D006801:Humans; D007249:Inflammation / Q000209:etiology; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D030101:Orthoreovirus, Avian / Q000472:pathogenicity*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012088:Reoviridae Infections / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D014709:Vero Cells
D053583:Interleukin-1beta; D015850:Interleukin-6; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D050796:STAT3 Transcription Factor