Reverse Genetics System for Heartland Bandavirus: NSs Protein Contributes to Heartland Bandavirus Virulence
Satoshi Taniguchi, Takuya Inagaki, Shigeru Tajima, Tadaki Suzuki, Tomoki Yoshikawa, Shuetsu Fukushi, Eun‐Sil Park, H Fujii, Shigeru Morikawa, Hideki Tani, Eri Nakayama, Takahiro Maeki, Masayuki Shimojima, Chang‐Kweng Lim, Masayuki Saijo
Abstract
Heartland bandavirus (HRTV) is a tick-borne virus identified in the United States in 2009. HRTV causes fever, fatigue, decreased appetite, headache, nausea, diarrhea, and muscle or joint pain in humans. FDA-approved vaccines and antiviral drugs are unavailable. The lack of a reverse genetics system hampers efforts to develop such antiviral therapeutics. Here, we developed a reverse genetics system for HRTV that led to the generation of a recombinant nonstructural protein (NSs)-knockout HRTV (rHRTV-NSsKO). We found that NSs interrupted signaling associated with innate immunity in HRTV-infected cells. Furthermore, rHRTV-NSsKO was highly attenuated and immunogenic in a mouse model. These findings suggest that NSs is a virulence factor of HRTV and that rHRTV-NSsKO could be a vaccine candidate for HRTV.