Two amino acid pairs in the glycoprotein of severe fever with thrombocytopenia syndrome virus responsible for the enhanced virulence

Severe fever with thrombocytopenia syndrome (SFTS) virus poses a major public health threat, with high mortality rates in both humans and cats. This study investigates the genetic factors underlying the differing virulence of SFTS virus (SFTSV) strains Tk-F123 and Ng-F264, isolated from cats. In type I interferon receptor-knockout mice, the Tk-F123 strain was uniformly lethal, while the Ng-F264 strain caused no fatalities. A critical difference was identified in the Gc protein: Tk-F123 encodes glycine and serine at residues 581 and 934, respectively, whereas Ng-F264 encodes arginine and asparagine at these positions. These amino acid differences significantly impact Gc protein function, modulating SFTSV virulence. These findings offer valuable insights into the molecular mechanisms of SFTSV pathogenicity and could guide the development of live-attenuated vaccines and antiviral therapies.
(SN)

Hsp90 β is critical for the infection of severe fever with thrombocytopenia syndrome virus

Severe fever with thrombocytopenia syndrome (SFTS) caused by the SFTS virus (SFTSV) is an emerging disease in East Asia with a fatality rate of up to 30%. SFTS is often characterized by an acute fever accompanied by thrombocytopenia and leukocytopenia, which can cause bleeding and severe consequences. The SFTSV genome is composed of three segments of single-stranded, negative-sense RNA, including large (L), middle (M), and small (S) segments. The S segment applies an ambisense strategy to encode nucleoprotein (NP) and nonstructural protein (NSs). NSs is a virulence factor of SFTSV. This study investigated the role of heat-shock protein 90 (Hsp90) during SFTSV infection. The association between NSs and Hsp90 isoforms was also explored. The data showed Hsp90 inhibitors could significantly inhibit the SFTSV infection markedly decreased the expression of the SFTSV encoded main virulence factor, NSs, in SFTSV infected cells. This study provides new insight into the regulation of NSs expression by host factors and suggests that Hsp90 inhibitors may exert therapeutic benefits for SFTS disease.
(DKW)

Identification of Host Factors for Rift Valley Fever Phlebovirus

A zoonotic pathogen Rift Valley Fever phlebovirus is well circulated among humans and livestock, characterized as causing abortion with almost 100% mortality rates in newborn animals. Presently, lack of FDA-approved antiviral drug/ license vaccine to control RFV in humans and detailed knowledge of viral protein function is necessary to successfully develop antiviral therapies. RVFV is susceptible to infect and replicate in a variety of cell types from frogs, pigs, elk, mule deer, reptiles. To analyze the host factor role, CRISPR-Cas9 knockout screening in A549 human cells and validated the function of the selected gene candidates by measuring the intracellular viral RNA accumulation, western blot, and RT-qPCR for two viruses, RVFV and La Crosse Encephalitis Virus (LACV). A gene knockout of member of WD repeat protein family (WDR7) in A549 human cell line is confirmed as important factor in the replication of two different viruses from Bunyavirales order. WDR7 gene disruption affects intracellular viral RNA accumulation primarily in the late phase of RVFV replication cycle and at the early phase of the LACV replication cycle. Moreover, the finding also highlight that WDR7 could be used as potential drug target for further antiviral development.
(INV)

In Vitro Infection Dynamics of Wuxiang Virus in Different Cell Lines

Wuxiang virus (WUXV) is classified in the order Bunyavirales, family Phenuiviridae, genus Phlebovirus. WUXV was isolated in 2018 in China from sandfly. WUXV-infected mice have been reported to exhibit severe neurological symptoms such as convulsions and limb rigidity. In some areas of China, healthy people and poultry retain WUXV-neutralizing antibodies, which may allow WUXV to infect people and poultry. The authors infected eight cell lines with WUXV and evaluated the virus growth characteristics in vitro. Significant CPE was observed in BHK-21, MDCK and PK-15 cells. Increases in viral titer, viral nucleic acid levels, and N antigen expression were also detected in seven infected cells. In contrast, Vero cells did not show CPE and other tests were negative. These results may provide a basis for further study of the mechanisms of WUXV transmission.
(SM)

Immune escape mechanisms of severe fever with thrombocytopenia syndrome virus

SFTSV belongs to the genus Bandavirus, family Phenuiviridae of the order Bunyavirales. SFTS is an emerging infectious disease that was first identified in China in 2009, and has been reported in many other countries and regions including Japan. It is mainly transmitted though the tick bite. Clinical symptoms of SFTS are persistent of high fever, thrombocytopenia, leukopenia and mortality rate is up to 30%. SFTSV has developed several mechanisms to escape host immune response. Example of the evasion mechanism of SFTSV from innate immunity include the impairment of mononuclear cells and dendritic cells, a decrease in number of NK cell, inhibition of the IFN signaling pathway, and the regulation of autophagy. Evasion from adaptive immunity involves a decrease in T cells, inhibition of antibody secretion and B cell maturation. Understanding the mechanism of immune evasion by SFTSV is essential for the development of vaccines and immunotherapy.
(TT)