Journal of Infectious Diseases and Medicine

Using Small Interfering RNAs, the Venezuelan Equine Encephalitis Virus is Inhibited

Abstract

Weidong Boghdeh

Due to a lack of efficient therapeutic intervention options, acutely contagious new world alphaviruses like the Venezuelan Equine Encephalitis Virus (VEEV) pose significant risks to the human population. Several in vitro and in vivo models of acute viral infections, including those involving alphaviruses like the Chikungunya virus and filoviruses like the Ebola virus, have shown that small interfering RNAs (vsiRNAs) that can specifically target the viral genome provide survival advantages. In this study, novel vsiRNAs were created and tested for antiviral efficacy in mammalian cells during VEEV infection. These vsiRNAs targeted conserved areas in the nonstructural and structural genes of the VEEV genome. The results show that vsiRNAs could successfully lower the infectious virus titer at earlier stages after infection. The inhibition was overcome at subsequent time points in the context of the virulent Trinidad Donkey strain and the attenuated TC-83 strain. The RISC complex's catalytic component, Argonaute 2 protein (Ago2), was depleted, negating the inhibitory effect of the vsiRNAs and highlighting the role of the siRNA route 3 were depleted, suggesting that the RNAi pathway plays a role in the development of a successful infection.