Natural or deliberate exposure to smallpox poses a great health threat, especially since routine smallpox vaccinations have been discontinued and no clinically approved treatment currently exists. In the February 1 issue of the Journal of Clinical Investigation, Ellis Reinherz and colleagues from Harvard Medical School propose a new antiviral therapy a low molecular weight inhibitor of signaling mediated by the smallpox growth factor (SPGF).
SPGF targets the erbB-1 signaling molecule, which normally initiates an intracellular cascade that facilitates viral replication. This study shows that drugs that interfere with erbB-1 signaling inhibit SPGF-induced viral replication and spread. The authors show that treatment with these erbB-1 inhibitors are effective in lowering morbidity and mortality, and boosting T cell immunity, in infected mice.
In an accompanying commentary, Anthony Fauci and Mark Challberg from the National Institutes of Health point out that this approach "may serve to turn the tables on the virus by interfering with the very pathways that are required for viral replication and extrusion."
This study demonstrates, for the first time, that chemical inhibition of host cell signaling pathways exploited by infectious agents represents a new avenue for development of anti-viral therapeutics. These inhibitors, which are already in use in human anti-tumor therapy, may have widespread applications in human viral infections and protection from smallpox. These findings reveal a new approach to the identification and development of antiviral compounds. This is especially critical at a time when the threat of smallpox as a biological weapon is high.
TITLE: Antiviral chemotherapy facilitates control of poxvirus infections through inhibition of cellular signal transduction