RNA sequencing of HTNV NP and Gc proteins expressing cells
Hantavirus infection has become a public health concern worldwide due to its ability to cause severe diseases in humans. The virulence of Hantavirus is determined by their ability to restrain host innate immune responses, such as type ? interferon (IFN-?) response. Here, we demonstrated that Hantaan virus (HTNV), a prevalent pathogen that causes hemorrhagic fever with renal syndrome in China, can inhibit host IFN-? production by manipulating the retinoic acid-induced gene I (RIG-I)-like receptor (RLRs) pathways. In brief, we performed the transcriptome analysis to identify the host factors regulated by nucleocapsid protein (NP) and glycoprotein (Gc) of HTNV, which showed that multiple cellular biological pathways were regulated by NP and Gc, including interferon signaling pathways, neuron differentiation, and response to mechanical stimulus. Further analysis demonstrated that HTNV NP and Gc proteins inhibited IFN-? response by targeting MAVS upstream molecules, such as RIG-I and MDA-5. Mechanistically, NP and Gc proteins suppressed RIG-I and MDA-5-induced IFN-? production by targeting TRIM25, rather than directly actin on RIG-I and MDA-5. Taken together, our study revealed a cross-talk between HTNV NP or Gc proteins and host innate immune response, which is helpful in the understanding of virus-host interaction in general. Overall design: To investigate the pathogenesis of HTNV coded NP and Gc proteins, we constructed GFP- and Flag- double-tagged HTNV NP and Gc plasmids for expression in mammalian cells. We transfected the plasmids expressing HTNV NP or Gc into HEK293T cells, and the GFP vector was used as a control. At 24 h post transfection, the GFP-positive cells were sorted and examined by RNA-seq analysis at Majorbio (http://www.majorbio.com/) (n=3).