HnRNP H1 binds to nucleocapsid protein and potential guanine-quadruplex site of viral RNA to promote PRRSV-2 proliferation.

Abstract

Porcine reproductive and respiratory syndrome (PRRS) is a highly contagious swine disease that causes huge economic losses to the pork industry worldwide. The heterogeneous nuclear ribonucleoprotein H1 (HnRNP H1) participates in a diverse range of cellular biological processes and has previously been reported to bind the nucleocapsid (N) protein of PRRSV-2; however, its role in PRRSV-2 proliferation remains largely unknown. Herein, we report that PRRSV-2 infection upregulated the cytoplasm expression levels of HnRNP H1 but decreased its abundance in the nucleus. Co-immunoprecipitation studies revealed an interaction between HnRNP H1 and the N protein. Furthermore, depletion of HnRNP H1 by siRNA significantly inhibited viral RNA levels, N protein expression, and virus yield in porcine alveolar macrophages (PAMs), whereas ectopic expression of HnRNP H1 favored such activities. Most importantly, we showed that HnRNP H1 binds to a potential guanine-quadruplex site (PGS) in PRRSV-2 negative-strand RNA, whereas the guanine-quadruplex ligand PhenDC3 abolished this interaction and significantly suppressed PRRSV-2 propagation. Collectively, our results demonstrate new functions of HnRNP H1 in facilitating PRRSV-2 proliferation and provide a potential option for combating PRRSV-2 infection by targeting the PGS.