A protease of the Venezuelan equine encephalitis virus (VEEV) was found to act on a host substrate in addition to the viral substrate. It is contemplated that these findings could be employed to facilitate post-translational silencing at the level of protein (removal of existing proteins) as a protein analog to CRISPR/Cas9 and RNAi/RISC, and further to enable detection of viral infection.

Methods and pharmaceutical compositions for preventing, treating or suppressing symptoms of a disorder associated with an alphavirus infection. In particular, the present invention relates to preventing, treating or suppressing symptoms of a disorder associated with an alphavirus infection through inhibiting the activity and/or expression of Transforming Growth Factor Beta (TGF-) in a subject suffering from or at risk for suffering from an alphavirus infection.

Proteases of Group IV (+)ssRNA viruses were found to act on a human sequences in addition to the viral sequences. The identity of the cleavable human sequences is disclosed. Detection of these sequences can act as a diagnostic of infection. It is contemplated that these findings could be employed to facilitate post-translational silencing at the level of protein (e.g., removal of existing proteins), thus serving as a protein analog to CRISPR/Cas9 and RNAi/RISC, and further to enable sequence-specific silencing of host functions without the modification of the host genome.