Host antiviral pathway – indirect modulation by ribavirin

The host antiviral pathway indirectly modulated by ribavirin refers to the complex set of cellular responses triggered by the drug to combat viral infections, distinct from its direct effects on viral enzymes. A primary component of this modulation is the inhibition of host Inosine-5'-monophosphate dehydrogenase (IMPDH), which depletes intracellular GTP pools necessary for viral RNA synthesis and cellular signaling (Graci & Cameron, 2006, Reviews in Medical Virology). Additionally, ribavirin is known to shift the host immune response from a Th2 to a Th1 profile, promoting the production of pro-inflammatory cytokines like IFN-gamma and TNF-alpha (Hultgren et al., 1998, Journal of General Virology). It also enhances the induction of interferon-stimulated genes (ISGs), which establish an "antiviral state" in host cells, making them more resistant to viral replication (Thomas et al., 2011, Hepatology). This multi-faceted host-targeted approach contributes to ribavirin's broad-spectrum efficacy against various RNA and DNA viruses, including Hepatitis C and respiratory syncytial virus. However, the systemic nature of these host modulations also underlies common side effects such as hemolytic anemia, caused by the accumulation of ribavirin triphosphate in erythrocytes (De Franceschi et al., 2000, Hepatology).

Other names

Ribavirin-induced host immune modulationIMPDH-mediated host antiviral responseInterferon-stimulated gene induction by ribavirinHost-targeted antiviral mechanism of ribavirin

Ribavirin modulates host antiviral pathways primarily through the inhibition of Inosine-5'-monophosphate dehydrogenase (IMPDH), leading to the depletion of intracellular GTP pools (Graci & Cameron, 2006), and by enhancing the expression of interferon-stimulated genes (ISGs) via the JAK-STAT signaling pathway (Thomas et al., 2011).