Antiviral Immune Pathway — RNA Interference

The RNA interference (RNAi) pathway is an important pathway in antiviral immunity involving a variety of mechanisms and responses. Viruses can evade this defense by encoding viral suppressors of RNAi (VSRs). For example, baculovirus P35 can inhibit cellular small interfering RNA (siRNA) pathways. It was found that Bombyx mori nucleopolyhedrovirus, the p35 protein of BmNPV, disrupts the function of siRNA by preventing the loading of siRNA into Argonaute-2 (Ago2) and enhances the replication of BmNPV. This wiki shares how BmNPV’s p35 protein restricts the host siRNA pathway.

p35 of BmNPV Restricts siRNA Pathway of the Host

Construction of pIZ-EGFP plasmid and dsRNA of EGFP (dsEGFP) co-transfected BmN cells to observe the efficiency of RNAi. The results showed that the p35 of BmNPV was involved in the inhibition of the cell’s siRNA pathway.

Fig 1. Cellular RNAi pathway is restricted by BmNPV p35

p35 Impedes Virus-Derived Small Interference RNA From Loading on Ago2

The effect of the b-elimination reaction was detected by Northern blot and transfected pIZ-p35-transfected cells. A significant portion of siEGFP was sensitive to b-elimination, evidenced by increased mobility on the gel, indicating that it was not loaded into Ago2.

Fig 2. p35 prevents siRNA from loading onto Ago2

Insects lack acquired immunity to specific viruses, and the RNAi pathway allows them to resist viral infection by capturing intermediates, which plays an important role in antiviral immunity. BmNPV’s p35 reduced the accumulation of virus-derived siRNA (vsiRNA) in specific regions of the viral genome, leading to increased expression of key genes in this region.

p35 disrupts siRNA function by preventing siRNA loading into Ago2. This inhibition of cellular RNAi enhances the expression of key genes and promotes BmNPV infection. It reduces the accumulation of vsiRNA mapped to the densely distributed genomic regions of the virus’s key genes, impedes the loading of Ago2 by vsiRNA and thus blocks the downstream function of antiviral RNAi reaction.

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Reference

Zhao Shudi, Chen Guanping, Kong Xiangshuo et al. BmNPV p35 Reduces the Accumulation of Virus-Derived siRNAs and Hinders the Function of siRNAs to Facilitate Viral Infection.[J] .Front Immunol, 2022, 13: 845268.