Results: PN3 Balb/c mice infected with 10 pfu of CHIKV developed the disease, with clinical symptoms progressing from day-3 post-infection (pi) and died on day 6-7 pi. The clinical manifestations started with lethargy (clinical score-1) on day 3; gradually progressed with alopecia and walking difficulties (score-2) on day 4; epileptic convulsions (score-3) on day 5; and death on day 6-7 (score-4) (Fig- 1). Peak viral load in brain was observed on day 6 by plaque assays, immediately prior to death (Fig- 2). The mRNA levels of IFN-␣ and IFN- were seen up regulated during the early days of infection, indicating a response to the ongoing viral replication in the brain tissues. TNF-␣ transcripts were up regulated at a moderate level at later days of infection. The most significant observation was the very high-level modulation of IL-1, a potent pro-inflammatory cytokine, and IFN-␥, an immune cytokine activating robust T-cell response (Fig- 3).
Conclusion:The cytokine transcripts IL-1 and IFN-␥, elucidated in response to the significant viral load in the brain, reached the peak level immediately prior to death in the animals indicating their key role in the fatal outcome of CNS infection with CHIKV.
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