HnRNP K reduces viral gene expression by targeting cytosine-rich sequences in porcine reproductive and respiratory syndrome virus-2 genome to dampen the viral growth

Abstract

HnRNP K is a well-known member of HnRNP family proteins that has been implicated in the regulation of protein expression. Currently, the impact of HnRNP K on the reproduction cycle of a broad range of virus were reported, while the precise function for PRRSV was lacking. In this study, we determined that both PRRSV infection and ectopic expression of N protein induced an enrichment of HnRNP K in the cytoplasm. Using RNA pulldown and RNA immunoprecipitation, we described the interactions between the KH2 domain of HnRNP K and cytosine-rich sequences (CRS) in PRRSV genomic RNA corresponding to Nsp7α coding region. Meanwhile, overexpression of HnRNP K inhibited viral gene expression and PRRSV replication, while silencing of HnRNP K resulted in an increased in virus yield. Taken together, this study assists in the understanding of PRRSV-host interactions, and the development of vaccines based on viral genome engineering.

Keywords: Cytosine-rich sequences (CRS); Heterogeneous nuclear ribonucleoprotein K (HnRNP K); Non-structural protein (Nsp) 7α; Porcine reproductive and respiratory syndrome virus (PRRSV); Replication.