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Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with high mortality (12%–30%). The mechanism by which the SFTS bunyavirus (SFTSV) causes severe illness remains unclear. To evaluate the phenotypic and functional characteristics of the NK cell subsets in SFTS patients, twenty-nine SFTS patients were sequentially sampled from admission until recovery. Phenotypic and functional characteristics of NK cell subsets in circulating blood were analysed via flow cytometry. Then, correlations between NK cell subset frequencies and the SFTS index (SFTSI) were evaluated in all SFTS patients (15 mild, 14 severe) upon admission. The frequencies of CD56dimCD16+ NK cells were greatly decreased in early SFTSV infection and were negatively correlated with disease severity. Additionally, higher Ki-67 and granzyme B expression and relatively lower NKG2A expression in CD56dimCD16+ NK cells were observed in acute infection. Moreover, the effector function of CD56dim NK cells was increased in the acute phase compared with the recovery phase in nine severe SFTS patients. Additionally, interleukin (IL)-15, interferon (IFN)-α, IL-18 and IFN-γ secretion was markedly increased during early infection. Collectively, despite depletion of CD56dimCD16+ NK cells, activation and functional enhancement of CD56dimCD16+ NK cells were still observed, suggesting their involvement in defence against early SFTSV infection.

Severe fever with thrombocytopenia syndrome virus (SFTSV), the causative agent of a febrile human disease, was first identified from central and eastern provinces in China, and later in Japan and South Korea. Hubei Province is one of the major SFTS epidemic areas in the central part of China. This study reported the isolation of 11 new SFTSV strains from patients in Hubei Province collected in 2017. Extensive phylogenetic analyses were conducted based on the complete coding sequences of SFTSV segments including the new strains. It was suggested that five different SFTSV genotypes were circulating in Hubei, and 15 reassortment patterns and migration pathways correlated with each genotype were identified, which was more than previously recognized. Hubei Province was more involved in the evolutionary events of SFTSV than that previously thought in which the evolutionary events of SFTSV were reported to be independent from those in other epidemic regions. Further divergence of SFTSV strains was suggested by pairwise comparison of SFTSV sequences from each genotype and sequence identity normalized to representative strain in genotype C1. Subsequently, amino acid variations specific for genotype(s), strain(s), or cluster(s) were inspected, which may be related to differential biological activity of SFTSV strains/genotypes. In conclusion, we analyzed the current status of SFTSV phylogeny in Hubei Province and discussed the possible events correlated to SFTSV evolution. It provided an in-depth insight into SFTSV evolution, raising concerns for the use of proper SFTSV strains in future studies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12250-020-00289-0) contains supplementary material, which is available to authorized users.

The newly emerged mosquito-borne Zika virus (ZIKV) strains pose a global challenge owing to its ability to cause microcephaly and neurological disorders. Several ZIKV vaccine candidates have been proposed, including inactivated and live attenuated virus vaccines, vector-based vaccines, DNA and RNA vaccines. These have been shown to be efficacious in preclinical studies in mice and nonhuman primates, but their use will potentially be a threat to immunocompromised individuals and pregnant women. Virus-like particles (VLPs) are empty particles composed merely of viral proteins, which can serve as a safe and valuable tool for clinical prevention and treatment strategies. In this study, we used a new strategy to produce ZIKV VLPs based on the baculovirus expression system and demonstrated the feasibility of their use as a vaccine candidate. The pre-membrane (prM) and envelope (E) proteins were co-expressed in insect cells and self-assembled into particles similar to ZIKV. We found that the ZIKV VLPs could be quickly and easily prepared in large quantities using this system. The VLPs were shown to have good immunogenicity in immunized mice, as they stimulated high levels of virus neutralizing antibody titers, ZIKV-specific IgG titers and potent memory T cell responses. Thus, the baculovirus-based ZIKV VLP vaccine is a safe, effective and economical vaccine candidate for use against ZIKV.

The Crimean-Congo hemorrhagic fever virus (CCHFV), a member of the genus Orthonairovirus and family Nairoviridae, is transmitted by ticks and causes severe hemorrhagic disease in humans. To study the epidemiology of CCHFV in different ecosystems in Xinjiang, China, a total of 58,932 ticks were collected from Tarim Basin, Junggar Basin, Tianshan Mountain, and Altai Mountain from 2014 to 2017. Hyalomma asiaticum asiaticum was the dominant tick species in Tarim and Junggar basins, whereas Dermacentor nuttalli and Hyalomma detritum were found in Tianshan Mountain and Altai Mountain, respectively. Reverse transcription-polymerase chain reaction of the CCHFV small (S) genome segment was used for the molecular detection. The CCHFV-positive percentage was 5.26%, 6.85%, 1.94%, and 5.56% in Tarim Basin, Junggar Basin, Tianshan Mountain, and Altai Mountain, respectively. Sequences of the S segment were used for phylogenetic analysis and the results showed that the newly identified CCHFV strains belonged to two clades. Our study confirms that H. asiaticum asiaticum is the major vector of CCHFV in desert habitats which is consistent with previous studies, and also suggests that H. detritum and D. nuttalli are emerging vectors for CCHFV in Xinjiang. Moreover, this study reports the presence of CCHFV in the mountain habitat of Xinjiang for the first time, suggesting that future surveillance of CCHFV should also include mountainous areas. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12250-018-0016-3) contains supplementary material, which is available to authorized users.

Hubei Province is a major epidemic area of severe fever with thrombocytopenia syndrome bunyavirus (SFTSV) in China. However, to date, a few SFTSV strains have been isolated from Hubei Province, preventing effective studies of epidemic outbreaks. Here, we report three confirmed patients (2015–2016) with typical symptoms of severe fever with thrombocytopenia syndrome disease (SFTS) who were farmers resident in different regions in Hubei Province. Three new SFTSV strains were isolated from the serum samples of each patient. Characterization of viral growth properties showed that there were no significant differences in virus production. All strains were completely sequenced, and phylogenetic analysis showed that unlike the other strains from Hubei province, which belonged to the SFTSV C3 genotype, one of the three strains belonged to the SFTSV C2 genotype. These results suggested that multiple SFTSV genotypes have been circulating in Hubei Province, providing insights into SFTSV evolution and improving our understanding of SFTSV prevalence in Hubei Province. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1007/s12250-017-3953-3 and is accessible for authorized users.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with high mortality (12%–30%). The mechanism by which the SFTS bunyavirus (SFTSV) causes severe illness remains unclear. To evaluate the phenotypic and functional characteristics of the NK cell subsets in SFTS patients, twenty-nine SFTS patients were sequentially sampled from admission until recovery. Phenotypic and functional characteristics of NK cell subsets in circulating blood were analysed via flow cytometry. Then, correlations between NK cell subset frequencies and the SFTS index (SFTSI) were evaluated in all SFTS patients (15 mild, 14 severe) upon admission. The frequencies of CD56(dim)CD16(+) NK cells were greatly decreased in early SFTSV infection and were negatively correlated with disease severity. Additionally, higher Ki-67 and granzyme B expression and relatively lower NKG2A expression in CD56(dim)CD16(+) NK cells were observed in acute infection. Moreover, the effector function of CD56(dim) NK cells was increased in the acute phase compared with the recovery phase in nine severe SFTS patients. Additionally, interleukin (IL)-15, interferon (IFN)-α, IL-18 and IFN-γ secretion was markedly increased during early infection. Collectively, despite depletion of CD56(dim)CD16(+) NK cells, activation and functional enhancement of CD56(dim)CD16(+) NK cells were still observed, suggesting their involvement in defence against early SFTSV infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12250-020-00224-3) contains supplementary material, which is available to authorized users.