Heartland virus (HRTV) is an emerging pathogenic phlebovirus (Phlebovirus genus, Phenuiviridae family, Bunyavirales order) first isolated from two Missouri farmers hospitalized with severe fever, leucopenia, and thrombocytopenia in 2009. HRTV is genetically closely related to the severe fever with thrombocytopenia syndrome virus (SFTSV), another highly pathogenic tick-borne phlebovirus emerging in China and the neighboring countries.

It is apparent that SFTSV, HRTV, and other related emerging phleboviruses have posed a severe threat to worldwide human health. However, there is currently no vaccine or medication available to prevent or treat these virus infections. Moreover, it is still poorly understood in terms of the phlebovirus-host interactions.

In a recent study, the research group led by Prof. WANG Hualin in Wuhan institute of Virology of the Chinese Academy of Sciences demonstrated that HRTV infection can block both type I and III IFN antiviral signaling. Furthermore, the mechanism underlying HRTV manipulation of type I and III IFN signaling was unraveled by detailed comparative studies in the context of HRTV infection and transient expression of potential IFN-inhibiting protein, HNSs. Finally, a function and mechanism model for IFN antagonism by HRTV as well as HNSs was proposed in comparison with SFTSV and SNSs.

Their findings suggest that HRTV and SFTSV, as well as their NSs proteins, appear to have potent and comparable capacity to destroy type I and III IFN antiviral responses (including both IFN induction and signaling), albeit by partly divergent strategies. The pathogenic risk of HRTV may need reassessment.  

Further comparative studies on these phleboviruses and their NSs proteins will provide clues to the molecular basis of the conservativeness and variance and promote the understanding of viral pathogenicity and virus-host interactions in evolutionary perspectives, thus likely benefiting the future development of specific or broadspectrum antiviral therapies.

This study was published in Journal of Biological Chemistry entitled “Heartland virus antagonizes type I and III interferon antiviral signaling by inhibiting phosphorylation and nuclear translocation of STAT2 and STAT1”.

Model for the disruption of type I and III IFN signaling by HRTV and HNSs, in comparison with SFTSV and SNSs. Image by NING Yunjia