Rodriguez, Moses

ABSTRACTTransgenic expression of the RNA-dependent RNA polymerase 3Dpolinhibited infection of Theiler's murine encephalitis virus (TMEV), a picornavirus from which it was derived. Here, we infected 3Dpoltransgenic mice with another picornavirus, as well as an alphaherpesvirus and a rhabdovirus. 3Dpoltransgenic FVB mice had significantly lower viral loads and survived longer after infection with all three types of viruses than nontransgenic FVB mice. Viral inhibition among three different types of virus by transgenic 3Dpolsuggests that the mechanism of action is not the direct interference with picornaviral 3Dpolbut instead may be the changing of host cells to an antiviral state before or after viral infection occurs, as basal interferon levels were higher in 3Dpoltransgenic mice before infection. Further study of this mechanism may open new possibilities for future antiviral therapy.

The RNA-dependent RNA-polymerase,3Dpol, is an essential component in the picornavirus genome for the replication of single stranded RNA. However, transgenic expression of3Dpolin mice has antiviral effects. Here, we discuss the structure and function of3Dpolduring picornavirus replication, we review the evidence and consequence of a host immune response to epitopes in3Dpolafter picornavirus infection, highlight data showing the antiviral effects of transgenic3Dpolfrom Theiler's murine encephalomyelitis virus (TMEV), and discuss potential mechanisms by which3Dpolis causing this antiviral effect in mice.