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Although climate change may expand the geographical distribution of several vector-borne diseases, the effects of environmental temperature in host defense to viral infection in vivo are unknown. Here, we demonstrate that exposure of mice to the high ambient temperature of 36 °C impaired adaptive immune responses against infection with viral pathogens, influenza, Zika, and severe fever with thrombocytopenia syndrome phlebovirus. Following influenza virus infection, the high heat-exposed mice failed to stimulate inflammasome-dependent cytokine secretion and respiratory dendritic cell migration to lymph nodes. Although commensal microbiota composition remained intact, the high heat-exposed mice decreased their food intake and increased autophagy in lung tissue. Induction of autophagy in room temperature-exposed mice severely impaired virus-specific CD8 T cells and antibody responses following respiratory influenza virus infection. In addition, we found that administration of glucose or dietary short-chain fatty acids restored influenza virus-specific adaptive immune responses in high heat-exposed mice. These findings uncover an unexpected mechanism by which ambient temperature and nutritional status control virus-specific adaptive immune responses.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease localized to China, Japan, and Korea that is characterized by severe hemorrhage and a high fatality rate. Currently, no specific vaccine or treatment has been approved for this disease. To develop a therapeutic agent for SFTS, we isolated antibodies from a phage-displayed antibody library that was constructed from a patient who recovered from SFTS virus (SFTSV) infection. One antibody, designated as Ab10, was reactive to the Gn envelope glycoprotein of SFTSV and protected host cells and A129 mice from infection in both in vitro and in vivo experiments. Notably, Ab10 protected 80% of mice, even when injected 5 days after inoculation with a lethal dose of SFTSV. Using cross-linker assisted mass spectrometry and alanine scanning, we located the non-linear epitope of Ab10 on the Gn glycoprotein domain II and an unstructured stem region, suggesting that Ab10 may inhibit a conformational alteration that is critical for cell membrane fusion between the virus and host cell. Ab10 reacted to recombinant Gn glycoprotein in Gangwon/Korea/2012, HB28, and SD4 strains. Additionally, based on its epitope, we predict that Ab10 binds the Gn glycoprotein in 247 of 272 SFTSV isolates previously reported. Together, these data suggest that Ab10 has potential to be developed into a therapeutic agent that could protect against more than 90% of reported SFTSV isolates.

Severe fever with thrombocytopenia syndrome virus (SFTSV), an emerging pathogen from the family Phenuiviridae , poses severe threats to public health in East Asia. In this study, we elucidate SFTSV’s epidemiological dynamics, transmission patterns, and molecular determinants of virulence, through analysis of 1942 genomes obtained from multiple host species across endemic regions in China, South Korea, Japan, and Thailand (2005–2023). Phylogenetic reconstruction delineates two major lineages (L1-Chinese and L2-Japanese-Korean) comprising 13 genotypes (I-XIII). Viral diversity is shaped by extensive segment-specific reassortment (212 events, including L1-L1, L2-L2, and L1-L2 patterns) and recombination (69 events, 62 in China). The M segment exhibited significantly elevated recombination frequency compared to the L and S segments. Geographically, Hubei province in China emerges as a reassortment hotspot with exceptional genotype diversity, while Henan, Hubei, and Zhejiang provinces serve as key recombination centers. Bayesian phylogeographic analysis traces the origin of SFTSV to the Jiangsu-Anhui border region (~17th century). Subsequent spread occurred through two distinct transmission networks: the L1 lineage disseminated terrestrially from Jiangsu-Anhui/Shandong to the Dabie Mountains and Liaoning province, while the L2 lineage dispersed via marine routes, with South Korea acting as a key transmission hub. Integration of clinical data identifies five positively selected sites and mortality-associated co-mutation networks that are enriched in the genotype IV, which is associated with mortality. Authors reconstruct the molecular evolution of severe fever with thrombocytopenia syndrome virus (SFTSV) in East Asia. SFTSV splits into two lineages with diversity driven by segment-specific reassortment; transmission occurs via distinct networks.

From June 2011 to August 2014, 21 cases of infection by severe fever with thrombocytopenia syndrome bunyavirus (SFTSV) were confirmed in Zhoushan Islands in the Eastern coast of China. To identify the source of SFTSV in Zhoushan Islands, the whole SFTSV genomes were amplified and sequenced from 17 of 21 patients. The L, M and S genomic segments of these SFTSV strains were phylogenetically analyzed together with those of 188 SFTSV strains available from GenBank. Phylogenetic analysis demonstrated SFTSV could be classified into six genotypes. The genotypes F, A and D were dominant in mainland China. Additionally, seven types of SFTSV genetic reassortants (abbreviated as AFA, CCD, DDF, DFD, DFF, FAF and FFA for the L, M and S segments) were identified from 10 strains in mainland China. Genotype B was dominant in Zhoushan Islands, Japan and South Korea, but not found in mainland China. Phylogeographic analysis also revealed South Korea possible be the origin area for genotype B and transmitted into Japan and Zhoushan islands in the later part of 20 th century. Therefore, we propose that genotype B isolates were probable transmitted from South Korea to Japan and Zhoushan Islands.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne viral disease caused by the SFTS virus (SFTSV) from Bunyaviridae that is endemic in East Asia. However, the genetic and evolutionary characteristics shared between tick- and human-derived Korean SFTSV strains are still limited. In this study we identify, for the first time, the genome sequence of a tick (Haemaphysalis longicornis)-derived Korean SFTSV strain (designated as KAGWT) and compare this virus with recent human SFTSV isolates to identify the genetic variations and relationships among SFTSV strains. The genome of the KAGWT strain is consistent with the described genome of other members of the genus Phlebovirus with 6,368 nucleotides (nt), 3,378 nt, and 1,746 nt in the Large (L), Medium (M) and Small (S) segments, respectively. Compared with other completely sequenced human-derived Korean SFTSV strains, the KAGWT strain had highest sequence identities at the nucleotide and deduced amino acid level in each segment with the KAGWH3 strain which was isolated from SFTS patient within the same region, although there is one unique amino acid substitution in the Gn protein (A66S). Phylogenetic analyses of complete genome sequences revealed that at least four different genotypes of SFTSV are co-circulating in South Korea, and that the tick- and human-derived Korean SFTSV strains (genotype B) are closely related to one another. Although we could not detect reassortant, which are commonly observed in segmented viruses, further large-scale surveillance and detailed genomic analysis studies are needed to better understand the molecular epidemiology, genetic diversity, and evolution of SFTSV. Full-length sequence analysis revealed a clear association between the genetic origins of tick- and human-derived SFTSV strains. While the most prevalent Korean SFTSV is genotype B, at least four different genotypes of SFTSV strains are co-circulating in South Korea. These findings provide information regarding the molecular epidemiology, genetic diversity, and evolution of SFTSV in East Asia.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne viral disease with high case–fatality rates in East Asia, yet no licensed vaccines are currently available. Here, we generated attenuated severe fever with thrombocytopenia syndrome virus (SFTSV) strains through serial passage in Huh-7 cells and evaluated their pathogenicity, immunogenicity, and protective efficacy. Attenuation candidates were selected based on reduced pathogenicity, estimated based on the median lethal dose (LD50), and genetic sequencing was performed to identify mutations associated with attenuation. In C57BL/6 IFNAR−/− mice, the attenuated strain exhibited markedly reduced virulence and viral loads while inducing robust virus-specific IgG, neutralizing antibody, and cellular immune responses. Notably, immunization with the attenuated strain conferred complete protection against lethal challenge with heterologous SFTSV genotypes. Genomic analysis revealed nonsynonymous mutations in the RNA-dependent RNA polymerase (RdRp), glycoprotein, and NSs genes, implicating alterations in viral replication, entry, and immune evasion. Collectively, these findings demonstrate that serial cell-culture passage can generate attenuated SFTSV strains that retain strong immunogenicity and cross-protective efficacy, supporting their potential as live-attenuated vaccine candidates for SFTS.

Severe Fever with Thrombocytopenia Syndrome (SFTS) is an emerging tick-borne infectious disease that poses a significant public health threat. SFTS virus (SFTSV) has a broad host range, including humans, cats, and natural reservoir species. Therefore, cultured cell lines derived from different mammalian species are useful for understanding the susceptibility of SFTSV in hosts. In this study, we evaluated pathogenicity and infectivity, focusing on cytopathic effect (CPE) induction and growth kinetics of SFTSV in several mammalian cell lines, including our original tiger-derived TLT, wild deer–derived DFKT and DFLT, and hedgehog-derived HHoVT. Following SFTSV infection, TLT, CRFK (cat), FCWF-4 (cat), and CPK (porcine) cells exhibited CPE, whereas Vero E6 (monkey), A549 (human), BHK-21 (hamster), DFKT, DFLT, and HHoVT cells did not. Infectious viral yields in the supernatants of TLT, CRFK, FCWF-4, Vero E6, and BHK-21 were higher than those of CPK, A549, DFLT, and DFKT. SFTSV infection in hedgehog-derived HHoVT cells was very limited. These observations suggest that features such as viral CPE and virus yield following SFTSV infection depend on cell type. It is noteworthy that TLT formed clear plaques that were easy to count, indicating that TLT cells are useful for the titration of infectious SFTSV by plaque-forming assay. Our results provide useful information and tools for further elucidating the mechanisms of SFTSV infectivity, proliferation, and pathogenicity using in vitro models.

The genus Phlebovirus of the family Bunyaviridae contains a number of emerging virus species which pose a threat to both human and animal health. Most prominent members include Rift Valley fever virus (RVFV), sandfly fever Naples virus (SFNV), sandfly fever Sicilian virus (SFSV), Toscana virus (TOSV), Punta Toro virus (PTV), and the two new members severe fever with thrombocytopenia syndrome virus (SFTSV) and Heartland virus (HRTV). The nonstructural protein NSs is well established as the main phleboviral virulence factor in the mammalian host. NSs acts as antagonist of the antiviral type I interferon (IFN) system. Recent progress in the elucidation of the molecular functions of a growing list of NSs proteins highlights the astonishing variety of strategies employed by phleboviruses to evade the IFN system.

Severe fever with thrombocytopenia syndrome (SFTS) is a newly emerging tick-borne infectious disease caused by the novel Bunyavirus/SFTS virus (SFTSV). The clinical manifestations mainly include fever, thrombocytopenia and multi-organ dysfunction, with a fatality rate as high as 30%. Since its first report in China in 2009, cases have subsequently emerged in multiple countries across East and Southeast Asia. SFTS demonstrates clear seasonal trends from May to November and tends to cluster geographically, mainly in hilly and mountainous areas. The virus is transmitted through tick bites, animal contact and human-to-human transmission. Its genetic diversity and frequent genetic recombination exacerbate public health threats. Pathogenic mechanism studies have shown that SFTSV uses glycoproteins Gn/Gc to mediate host cell invasion. In the early stage, the virus uses its non-structural protein NSs to inhibit innate immune signal transduction. Massive replication of the virus leads to excessive immune activation, triggering cytokine storms and abnormal platelet activation, and eventually resulting in bleeding and multiple organ failure. The clinical management primarily relies on supportive care, while broad-spectrum antiviral drugs and neutralizing antibodies remain investigational. Although numerous vaccine candidates have been designed and developed, none have progressed to clinical trials. This review systematically integrates current knowledge spanning virology, epidemiology, pathogenic mechanisms, therapeutic interventions and vaccine development, offering actionable insights for public health strategies and clinical practice.

Bunyavirus ribonucleoprotein (RNP) that is assembled by polymerized nucleoproteins (N) coating a viral RNA and associating with a viral polymerase can be both the RNA synthesis machinery and the structural core of virions. Bunyaviral N and RNP thus could be assailable targets for host antiviral defense; however, it remains unclear which and how host factors target N/RNP to restrict bunyaviral infection. By mass spectrometry and protein-interaction analyses, we here show that host protein MOV10 targets the N proteins encoded by a group of emerging high-pathogenic representatives of bunyaviruses including severe fever with thrombocytopenia syndrome virus (SFTSV), one of the most dangerous pathogens listed by World Health Organization, in RNA-independent manner. MOV10 that was further shown to be induced specifically by SFTSV and related bunyaviruses in turn inhibits the bunyaviral replication in infected cells in series of loss/gain-of-function assays. Moreover, animal infection experiments with MOV10 knockdown corroborated the role of MOV10 in restricting SFTSV infection and pathogenicity in vivo . Minigenome assays and additional functional and mechanistic investigations demonstrate that the anti-bunyavirus activity of MOV10 is likely achieved by direct impact on viral RNP machinery but independent of its helicase activity and the cellular interferon pathway. Indeed, by its N-terminus, MOV10 binds to a protruding N-arm domain of N consisting of only 34 amino acids but proving important for N function and blocks N polymerization, N-RNA binding, and N-polymerase interaction, disabling RNP assembly. This study not only advances the understanding of bunyaviral replication and host restriction mechanisms but also presents novel paradigms for both direct antiviral action of MOV10 and host targeting of viral RNP machinery.