In vitro studies in HBV cell culture systems have demonstrated that inarigivir has the ability to prevent viral replication by inhibiting HBV replication at the level of reverse transcription and/or blocking priming or subsequent primer translocation within the viral nucleocapsid, which appears independent of the RIG-I mediated activation of IRF-3
and cytokine activation.
Among the 9 IRFs, IRF-3 and IRF-7 are the master regulators of IFN-I.
When mice deficient in either IRF-3 or IRF-7 were infected with PbA sporozoite, significant impairment in IFN-I response was observed.
Unlike IRF-3 and IRF-7, expression of IRF-8 is induced by IFN-[gamma] instead of IFN-I.
One mechanism of inhibition is prevention of interferon regulatory factor 3's (IRF-3
) ability to activate antiviral genes.
IRF-1 IRF-2 IRF-3
Mean 20.03 20.35 12.81 SD 3.36 2.60 1.73 % CV 17 13 13 UOM 0.34 0.26 0.26
The N- and C-terminal domains of the NS1 protein of influenza B virus can independently inhibit IRF-3
and beta interferon promoter activation.
Inhibition of IRF-3 promotes viral persistence after the initial infection and may reduce the effectiveness of interferon therapies.
may also restore the responsiveness of the IRF-3 pathway" (Science [online], 2003; www.sciencemag.org/sciencexpress/recent.shtml).
It was found that both NF-[kappa]B and IRF-3 activate IFN-[beta] gene transcription while IFN-[alpha] gene expression is entirely based on IRFs .
IRF-3. IRF-3 was discovered by searching genes with homology sequences with IRF-1 and IRF-2 .
IRF-7, together with IRF-3, is a 503-amino acid central and nonredundant mediator of viral nucleic acid-induced induction of IFN-[alpha] [19, 86, 87].