Intracranial Administration of P Gene siRNA Protects Mice from Lethal Chandipura Virus Encephalitis

Kumar, Satyendra; Arankalle, Vidya A.

IFN has been shown to have antiviral effect both against VSV [41] and CHPV [42] as evidenced by in-vitro and human studies respectively. Fig 10a clearly documents excessive upregulation of IFN gene in the early stages of the infection (24hr PI) followed by drastic decrease. Thus, though IFN is produced in large quantities to combat the infection, desired effect was not achieved leading to death. Importantly, no elevation was recorded in virus-infected P-2 siRNA treated as well as control mice receiving the vehicle alone. IL-10, involved in the suppression of the protective immune response was elevated in the initial phase and at the time of death. This cytokine might be playing crucial role in the pathogenesis of CHPV. The elevated expression of TNF and IL-1b were found to decrease with time that is consistent with a previous report documenting susceptibility of TNF-a and IL-1b knockout (KO) mice to lethal HSV-1 encephalitis [43] . SOCS-1, the suppressor of cytokine signaling gene playing a critical role in the negative regulation of cytokine signaling was steadily decreasing after initial elevation. These results are similar to a study with rabies virus infection wherein downregulation of SOCS-1 gene was shown [44] .